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  • 1. Khan, Tanweera
    et al.
    Sundin, Anders
    Juhlin, Claes
    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.
    Långström, Bengt
    Bergström, Mats
    Eriksson, Barbro
    11C-metomidate PET imaging of adrenocortical cancer2003In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, Vol. 30, 403-410 p.Article in journal (Refereed)
  • 2.
    Lundberg, Peter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Radio Physics. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics.
    Ekblad, Alf
    Nilsson, Mats
    13C NMR spectroscopy studies of forest soil microbial activity: Glucose uptake and fatty acid biosynthesis2001In: Soil Biology and Biochemistry, ISSN 0038-0717, Vol. 33, no 4-5, 621-632 p.Article in journal (Refereed)
    Abstract [en]

    The intimate association of soil microorganisms with the soil matrix complicates analysis of their metabolism, since thorough separation of intact cells from the matrix is very difficult using standard protocols. Thus, in the study reported here, in situ glucose decomposition and metabolism in humus from a coniferous forest soil was monitored and evaluated using 'solution state' 13C NMR, which can be used in a non-invasive manner. [U-13C] glucose was added at a concentration of 1.73 mmol C g-1 dry organic matter, which is known to allow maximal substrate induced respiration (SIR), and the microbial metabolism of the added C was followed over a period of 28 days. The data showed that ~50% of the added glucose was consumed within three days, coinciding with the appearance of label in CH3, -CH2- and -CH = CH-groups, and in glycerol-carbons, suggesting that olefinic triacylglycerols were being formed, probably located in oil droplets. During days two to three, around 40% of the consumed glucose C was allocated into solid state components, about 40% was respired and about 20% was found as triglycerols. The triacylglycerol signal reached a maximum after 13 days, but subsequently declined by 60%, as the triacylglycerols were apparently consumed, by day 28 of the incubation. Our results indicate there was an initial formation of structural microbial C (solid state carbon) followed by formation of storage lipid C, which subsequently decreased, probably because it was used to provide the organisms with energy when the external energy source (i.e. the glucose) was depleted. The formation of unsaturated triacylglycerols, typical storage metabolites of eucaryotes, suggests that fungi were the most active organisms in the glucose degradation. ⌐ 2001 Elsevier Science Ltd.

  • 3.
    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.

  • 4.
    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.

  • 5.
    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.

  • 6.
    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.

  • 7.
    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.

  • 8.
    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.

  • 9.
    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.

  • 10.
    Wijma, Barbro
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gender and medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Sjögren, Berit
    Karolinska sjukhuset, Stockholm.
    1900-talet och psykosocial obstetrik, gynekologi och sexologi2004In: Svensk kvinnosjukvård under ett sekel: [1904-2004 : jubileumsskrift] / [ed] Bo Lindberg, Stockholm: SFOG , 2004, -248 p.Chapter in book (Other academic)
  • 11.
    Carlsson Tedgren, Åsa
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Radiation Physics . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics.
    Grindborg, J-E
    Stockholm.
    192-Ir source strength dosimetry audit in Sweden2007In: 9th Biennial ESTRO meeting on physics and radiation technology for clinical radiotherapy,2007, 2007, S143-S143 p.Conference paper (Other academic)
    Abstract [en]

    Posters Brachytherapy, publicerad i Radiotherapy and Oncology.

  • 12.
    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.

  • 13.
    du Bois, A
    et al.
    Department of Gynecology & Gynecologic Oncology, Wiesbaden, Germany..
    Quinn, M
    Thigpen, T
    Vermorken, J
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Bookman, M
    Bowtell, D
    Brady, M
    Casado, A
    Cervantes, A
    Eisenhauer, E
    Friedlaender, M
    Fujiwara, K
    Grenman, S
    Guastalla, J P
    Harper, P
    Hogberg, T
    Kaye, S
    Kitchener, H
    Kristensen, G
    Mannel, R
    Meier, W
    Miller, B
    Neijt, J P
    Oza, A
    Ozols, R
    Parmar, M
    Pecorelli, S
    Pfisterer, J
    Poveda, A
    Provencher, D
    Pujade-Lauraine, E
    Randall, M
    Rochon, J
    Rustin, G
    Sagae, S
    Stehman, F
    Stuart, G
    Trimble, E
    Vasey, P
    Vergote, I
    Verheijen, R
    Wagner, U
    2004 consensus statements on the management of ovarian cancer: final document of the 3rd International Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference (GCIG OCCC 2004).2005In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 16, no 8, viii7-viii12 p.Article in journal (Refereed)
  • 14.
    Horner, Patrick J
    et al.
    School of Social and Community Medicine, University of Bristol, UK.
    Karla, Blee
    Bristol Sexual Health Centre, University Hospitals Bristol NHS Foundation Trust, UK.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    van der Meijden, W
    Department of Dermatology, New Cross Hospital, UK..
    Moi, H.
    Olafia Clinic, Oslo University Hospital, Institute of Medicine, University of Oslo, Norway.
    2016 European Guideline on the management of non-gonococcal urethritis2016In: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, Vol. 27, no 11, 928-937 p.Article in journal (Refereed)
    Abstract [en]

    We present the updated International Union against Sexually Transmitted Infections guideline for the management of non-gonococcal urethritis in men. This guideline recommends confirmation of urethritis in symptomatic men before starting treatment. It does not recommend testing asymptomatic men for the presence of urethritis. All men with urethritis should be tested for Chlamydia trachomatis and Neisseria gonorrhoeae and ideally M. genitalium using a NAAT as this is highly likely to improve clinical outcomes. If a NAAT is positive for gonorrhoea, a culture should be performed before treatment. In view of the increasing evidence that azithromycin 1 g may result in the development of antimicrobial resistance in Mycoplasma genitalium azithromycin 1 g is no longer recommended as first line therapy, which should be doxycycline 100 mg bd for 7 days. If azithromycin is to be prescribed an extended of 500 mg, then 250 mg daily for 4 days is to be preferred over 1 g stat. In men with persistent NGU, M. genitalium NAAT testing is recommended if not previously undertaken, as is Trichomonas vaginalis NAAT testing in populations where T. vaginalis is detectable in >2% of symptomatic women.

  • 15.
    Larsby, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences.
    20:e internationella audiologikongressen. Intressanta resultat om binaural hörsel.1991In: Audio Nytt, Vol. 18, 30-31 p.Article in journal (Other (popular science, discussion, etc.))
  • 16.
    Tondel, Martin
    et al.
    University of Gothenburg.
    Murgia, Nicola
    University of Perugia.
    Persson, Bodil
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Occupational and Environmental Medicine Centre.
    Lindh, Jonas
    Ryhov County Hospital.
    Vrethem, Magnus
    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.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    2,5-Hexanedione in the General Population: Environmental Exposure or Endogenous Production? in EPIDEMIOLOGY, vol 22, issue 1, pp S34-S352011In: EPIDEMIOLOGY, Williams and Wilkins , 2011, Vol. 22, no 1, S34-S35 p.Conference paper (Refereed)
    Abstract [en]

    n/a

  • 17.
    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.

  • 18.
    Forsgren, Mikael
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Bengtsson, Ann
    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.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Sören, Birgitta
    Linköping University, Department of Medical and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences.
    Brandejsky, Vaclav
    Depts Clinical Research and Radiology, University Bern, Bern, Switzerland.
    Lund, Eva
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    31P MRS as a Potential Biomarker for Fibromyalgia2012In: Proceedings of the 20th Annaal Meeting & Exhibition, 5-11 May, Melbourne, Australia, 2012, 1493-1493 p.Conference paper (Refereed)
    Abstract [en]

    Major clinical symptoms in fibromyalgia (FM) are muscle pain, stiffness and fatigue. Studies have shown reduced voluntary strength and exercise capacity, lower endurance and more muscular pain even at low workload. An impaired muscle energy metabolism has therefore been proposed as a result of the disease. An earlier study using magnetic resonance spectroscopy (MRS) showed that at maximal dynamic and static contractions the concentration of inorganic phosphate was lower in FM [1]. A decrease in ATP, ADP and PCr and an increase in AMP and creatine was found in FM biopsies [2]. The purpose of this study was to non-invasively analyze the quantitative content of  phosphagens in the resting muscle in FM in comparison to healthy controls using 31P MRS of the quadriceps muscle.

  • 19.
    Li, Wei
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences.
    Yuan, Ximing
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Ivanova, S.
    Laboratory of Biomedical Science, North Shore-LIE Research Institute, Manhasset, NY 11030, United States.
    Tracey, K.J.
    Laboratory of Biomedical Science, North Shore-LIE Research Institute, Manhasset, NY 11030, United States.
    Eaton, John Wallace
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Brunk, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Pharmacology .
    3-Aminopropanal, formed during cerebral ischaemia, is a potent lysosomotropic neurotoxin2003In: Biochemical Journal, ISSN 0264-6021, Vol. 371, no 2, 429-436 p.Article in journal (Refereed)
    Abstract [en]

    Cytotoxic polyamine-derived amino aldehydes, formed during cerebral ischaemia, damage adjacent tissue (the so-called 'penumbra') not subject to the initial ischaemic insult. One such product is 3-aminopropanal (3-AP), a potent cytotoxin that accumulates in ischaemic brain, although the precise mechanisms responsible for its formation are still unclear. More relevant to the present investigations, the mechanisms by which such a small aldehydic compound might be cytotoxic are also not known, but we hypothesized that 3-AP, having the structure of a weak lysosomotropic base, might concentrate within lysosomes, making these organelles a probable focus of initial toxicity. Indeed, 3-AP leads to lysosomal rupture of D384 glioma cells, a process which clearly precedes caspase activation and apoptotic cell death. Immunohistochemistry reveals that 3-AP concentrates in the lysosomal compartment and prevention of this accumulation by the lysosomotropic base ammonia, NH3, protects against 3-AP cytotoxicity by increasing lysosomal pH. A thiol compound, N-(2-mercaptopropionyl)glycine, reacts with and neutralizes 3-AP and significantly inhibits cytoxocity. Both amino and aldehyde functions of 3-AP are necessary for toxicity: the amino group confers lysosomotropism and the aldehyde is important for additional, presently unknown, reactions. We conclude that 3-AP exerts its toxic effects by accumulating intralysosomally, causing rupture of these organelles and releasing lysosomal enzymes which initiate caspase activation and apoptosis (or necrosis if the lysosomal rupture is extensive). These results may have implications for the development of new therapeutics designed to lessen secondary damage arising from focal cerebral ischaemia.

  • 20.
    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.

  • 21.
    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.

  • 22.
    Kovacsovics, Bea
    et al.
    Linköping University, Department of Medicine and Care.
    Davidsson, L
    Harder, Henrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Magnusson, B
    Ledin, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    3D FSE T2 MR bilder vid ponsvinkelundersökningar2000In: Vårmöte i Linköping 18-19/5 2000 / Svensk förening för otorhinolaryngologi, huvud halskirurgi,2000, 2000Conference paper (Other academic)
  • 23.
    Steen, Alexander
    et al.
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, The Institute of Technology.
    Widegren, Marcus
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, The Institute of Technology.
    3D Visualization for Pre-operative Planning of Orthopedic Surgery2013Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This report presents a master thesis on 3D visualization for pre-operation planning of orthopedic surgery done for Sectra Medical Systems AB. The focus is on visualizing clinically relevant data for planning a Total Hip Replacement (THR). The thesis includes a pre-study and the implementation of a prototype using the Sectra IDS7 workstation.

  • 24.
    Shah, Ashesh
    et al.
    Institute for Medical and Analytical Technologies, University of Applied Sciences and Art Northwestern Switzerland.
    Alonso, Fabiola
    Linköping University, Department of Biomedical Engineering.
    Pison, Daniela
    Institute for Medical and Analytical Technologies, University of Applied Sciences and Art Northwestern Switzerland, Muttenz.
    Lemaire, Jean-Jacques
    Centre Hospitalier Universitaire de Clermont-Ferrand, Image-Guided Clinical Neurosciences and Connectomics (EA 7282, IGCNC), Université d’Auvergne.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering.
    Coste, Jérôme
    Centre Hospitalier Universitaire de Clermont-Ferrand, Image-Guided Clinical Neurosciences and Connectomics (EA 7282, IGCNC), Université d’Auvergne.
    Schkommodau, Erik
    Institute for Medical and Analytical Technologies, University of Applied Sciences and Art Northwestern Switzerlan.
    Hemm-Ode, Simone
    Linköping University, Department of Biomedical Engineering. Institute for Medical and Analytical Technologies and Department of Biomedical Engineering, University of Applied Sciences and Art Northwestern Switzerland .
    3D Visualization of intraoperative stimulation test results for better target selection in DBS surgery2016Conference paper (Refereed)
  • 25. Stuart, G
    et al.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    du Bois, A
    Bookman, M
    Bowtell, D
    Brady, M
    Casado, A
    Cervantes, A
    Eisenhauer, E
    Friedlaender, M
    Fujuwara, K
    Grenman, S
    Guastalla, JP
    Harper, P
    Högberg, Thomas
    NSGO (Scandinavia).
    Kaye, S
    Kitchener, H
    Kristensen, G
    Mannel, R
    Meier, W
    Miller, B
    Oza, A
    Ozols, R
    Parmar, M
    Pfisterer, J
    Poveda, A
    Provencher, D
    Pujade-Lauraine, E
    Quinn, M
    Randall, M
    Rochon, J
    Rustin, G
    Sagae, S
    Stehman, F
    Trimble, E
    Thigpen, T
    Vasey, P
    Vergote, I
    Verheijen, R
    Vermorken, J
    Wagner, U
    3rd international ovarian cancer consensus conference: outstanding issues for future consideration2005In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 16, no supplement 8, viii36-viii38 p.Article in journal (Refereed)
  • 26.
    Nylander, Göran
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Carlström, C
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Adolfsson, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    4,5 year follow-up after surgical correction of upper extremity deformities in spastic cerebral palsy.1999In: Journal of Hand Surgery - British and European Volume, ISSN 0266-7681, Vol. 24, 719-723 p.Article in journal (Refereed)
  • 27.
    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.

  • 28.
    Dyverfeldt, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bissell, Malenka
    University of Oxford, England.
    Barker, Alex J.
    Northwestern University, IL 60611 USA.
    Bolger, Ann F
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. University of Calif San Francisco, CA USA.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Francios, Christopher J.
    University of Wisconsin, WI 53706 USA.
    Frydrychowicz, Alex
    University Hospital Schleswig Holstein, Germany.
    Geiger, Julia
    University of Childrens Hospital Zurich, Switzerland.
    Giese, Daniel
    University Hospital Cologne, Germany.
    Hope, Michael D.
    University of Calif San Francisco, CA USA.
    Kilner, Philip J.
    University of London Imperial Coll Science Technology and Med, England.
    Kozerke, Sebastian
    University of Zurich, Switzerland; ETH, Switzerland.
    Myerson, Saul
    University of Oxford, England.
    Neubauer, Stefan
    University of Oxford, England.
    Wieben, Oliver
    University of Wisconsin, WI 53706 USA.
    Markl, Michael
    Northwestern University, IL 60611 USA; Northwestern University, IL 60611 USA.
    4D flow cardiovascular magnetic resonance consensus statement2015In: Journal of Cardiovascular Magnetic Resonance, ISSN 1097-6647, E-ISSN 1532-429X, Vol. 17, no 72Article, review/survey (Refereed)
    Abstract [en]

    Pulsatile blood flow through the cavities of the heart and great vessels is time-varying and multidirectional. Access to all regions, phases and directions of cardiovascular flows has formerly been limited. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has enabled more comprehensive access to such flows, with typical spatial resolution of 1.5x1.5x1.5 - 3x3x3 mm(3), typical temporal resolution of 30-40 ms, and acquisition times in the order of 5 to 25 min. This consensus paper is the work of physicists, physicians and biomedical engineers, active in the development and implementation of 4D Flow CMR, who have repeatedly met to share experience and ideas. The paper aims to assist understanding of acquisition and analysis methods, and their potential clinical applications with a focus on the heart and greater vessels. We describe that 4D Flow CMR can be clinically advantageous because placement of a single acquisition volume is straightforward and enables flow through any plane across it to be calculated retrospectively and with good accuracy. We also specify research and development goals that have yet to be satisfactorily achieved. Derived flow parameters, generally needing further development or validation for clinical use, include measurements of wall shear stress, pressure difference, turbulent kinetic energy, and intracardiac flow components. The dependence of measurement accuracy on acquisition parameters is considered, as are the uses of different visualization strategies for appropriate representation of time-varying multidirectional flow fields. Finally, we offer suggestions for more consistent, user-friendly implementation of 4D Flow CMR acquisition and data handling with a view to multicenter studies and more widespread adoption of the approach in routine clinical investigations.

  • 29.
    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.

  • 30.
    Casas Garcia, Belén
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lantz, Jonas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    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.
    4D Flow MRI-Based Pressure Loss Estimation in Stenotic Flows: Evaluation Using Numerical Simulations2016In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 75, no 4, 1808-1821 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To assess how 4D flow MRI-based pressure and energy loss estimates correspond to net transstenotic pressure gradients (TPG(net)) and their dependence on spatial resolution. Methods: Numerical velocity data of stenotic flow were obtained from computational fluid dynamics (CFD) simulations in geometries with varying stenosis degrees, poststenotic diameters and flow rates. MRI measurements were simulated at different spatial resolutions. The simplified and extended Bernoulli equations, Pressure-Poisson equation (PPE), and integration of turbulent kinetic energy (TKE) and viscous dissipation were compared against the true TPG(net). Results: The simplified Bernoulli equation overestimated the true TPG(net) (8.74 +/- 0.67 versus 6.76 +/- 0.54 mmHg). The extended Bernoulli equation performed better (6.57 +/- 0.53 mmHg), although errors remained at low TPG(net). TPG(net) estimations using the PPE were always close to zero. Total TKE and viscous dissipation correlated strongly with TPG(net) for each geometry (r(2) &gt; 0.93) and moderately considering all geometries (r(2) = 0.756 and r(2) = 0.776, respectively). TKE estimates were accurate and minorly impacted by resolution. Viscous dissipation was overall underestimated and resolution dependent. Conclusion: Several parameters overestimate or are not linearly related to TPG(net) and/or depend on spatial resolution. Considering idealized axisymmetric geometries and in absence of noise, TPG(net) was best estimated using the extended Bernoulli equation. (C) 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance.

  • 31.
    Evaldsson, Chamilly
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Rydén, Ingvar
    Division of Clinical Chemistry, Kalmar County Hospital, Kalmar, Sweden.
    Rosén, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Uppugunduri, Srinivas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    4-Thiouridine induces dose-dependent reduction of oedema, leucocyte influx and tumour necrosis factor in lung inflammation2009In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 155, no 2, 330-338 p.Article in journal (Refereed)
    Abstract [en]

    Recent reports demonstrate a role for nucleotides as inflammatory modulators. Uridine, for example, reduces oedema formation and leucocyte infiltration in a Sephadex-induced lung inflammation model. Tumour necrosis factor (TNF) concentration was also reduced. Previous in vivo observations indicated that 4-thiouridine might have similar effects on leucocyte infiltration and TNF release. The aim of this study was thus to investigate the effects of 4-thiouridine in greater detail. We used a Sephadex-induced acute lung inflammation model in Sprague-Dawley rats. The dextran beads were instilled intratracheally into the lungs, which were excised and examined after 24 h. Sephadex alone led to massive oedema formation and infiltration of macrophages, neutrophils and eosinophils. Microgranulomas with giant cell formations were clearly visible around the partially degraded beads. A significant increase in bronchoalveolar lavage fluid (BALF) content of TNF and leukotrienes was also seen. 4-Thiouridine co-administration affected all variables investigated in this model, i.e. oedema, microscopic and macroscopic appearance of lung tissue, total leucocyte and differential leucocyte counts in BALF, TNF and leukotrienes C-4 (LTC4), LTD4 and LTE4 in BALF, indicating a reproducible anti-inflammatory effect. In conclusion, we have demonstrated that 4-thiouridine has anti-inflammatory effects similar to those of uridine. To our knowledge, this is the first demonstration of pharmacological 4-thiouridine effects in vivo. The results suggest nucleoside/nucleotide involvement in inflammatory processes, warranting further studies on nucleoside analogues as attractive new alternatives in the treatment of inflammatory diseases.

  • 32.
    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.

  • 33. Sastry, M
    et al.
    Gustafsson, Håkan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Radiation Physics.
    Lund, Anders
    Linköping University, Department of Physics, Chemistry and Biology.
    Lund, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Radiation Physics. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Radiation Physics.
    51V(n,β)52Cr reaction for neutron dosimetry: Development and assessment of a spectrophotometric method for determination of Cr in vanadium at sub ppm level2004In: Spectrochimica Acta Part A - Molecular and Biomolecular Spectroscopy, ISSN 1386-1425, Vol. 60, no 10, 2363-2367 p.Article in journal (Refereed)
    Abstract [en]

    With a view to monitoring the changes in coloration caused by the nuclear reaction 51V(n,β)52Cr in solution of vanadyl sulphate and using it for neutron dosimetry, electronic absorption spectra of vanadyl sulphate solutions were investigated at different concentrations of chromate impurity in micromolar range. It was observed that the presence of chromate enhances the absorptivity over a wide wavelength range serving essentially as a colouring agent for vanadium matrix, presumably due to charge transfer process. The absorbance at 380nm varied linearly over a wide concentration range. The limit of detection of chromate obtained is shown to be adequate for detecting neutron-induced chemical transmutation of vanadium to chromium under standard reactor conditions, when used with long path length cells. It was observed that the absorbance does not change on electron irradiation, suggesting that radiolytic effects due to beta decay, if any, do not interfere in the measurement of neutron-induced changes. In addition to its potential for neutron dosimetry, this is the first report of a simple and direct method of estimation of Cr in vanadium matrix at sub ppm level.

  • 34.
    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.

  • 35. Helander, A
    et al.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry.
    5-HTOL - ny biokemisk alkoholmarkör med rättsmedicinska tillämpningar2002In: Läkartidningen, ISSN 0023-7205, Vol. 99, 3950-3954 p.Article in journal (Other academic)
  • 36.
    Nestor, Colm
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lentini, Antonio
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Hägg Nilsson, Cathrine
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Gawel, Danuta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Mika
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Mattson, Lina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Wang, Hui
    MD Anderson Cancer Centre, TX 77030 USA.
    Rundquist, Olof
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Meehan, Richard R.
    University of Edinburgh, Scotland.
    Klocke, Bernward
    Genomatix Software GmbH, Germany.
    Seifert, Martin
    Genomatix Software GmbH, Germany.
    Hauck, Stefanie M.
    German Research Centre Environm Health GmbH, Germany.
    Laumen, Helmut
    Technical University of Munich, Germany; Technical University of Munich, Germany; Helmholtz Zentrum Munchen, Germany; Technical University of Munich, Germany; Technical University of Munich, Germany.
    Zhang, Huan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Benson, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    5-Hydroxymethylcytosine Remodeling Precedes Lineage Specification during Differentiation of Human CD4(+) T Cells2016In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 16, no 2, 559-570 p.Article in journal (Refereed)
    Abstract [en]

    5-methylcytosine (5mC) is converted to 5-hydroxymethylcytosine (5hmC) by the TET family of enzymes as part of a recently discovered active DNA de-methylation pathway. 5hmC plays important roles in regulation of gene expression and differentiation and has been implicated in T cell malignancies and autoimmunity. Here, we report early and widespread 5mC/5hmC remodeling during human CD4(+) T cell differentiation ex vivo at genes and cell-specific enhancers with known T cell function. We observe similar DNA de-methylation in CD4(+) memory T cells in vivo, indicating that early remodeling events persist long term in differentiated cells. Underscoring their important function, 5hmC loci were highly enriched for genetic variants associated with T cell diseases and T-cell-specific chromosomal interactions. Extensive functional validation of 22 risk variants revealed potentially pathogenic mechanisms in diabetes and multiple sclerosis. Our results support 5hmC-mediated DNA de-methylation as a key component of CD4(+) T cell biology in humans, with important implications for gene regulation and lineage commitment.

  • 37.
    Svensson Holm, Ann-Charlotte
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Berg, Cecilia
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Herbertsson, Helena
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Söderström, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Hammarström, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Lindström, Eva
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Bengtsson, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    5-Lipoxygenase activity is involved in platelet-induced fibroblast proliferation2006Conference paper (Refereed)
  • 38.
    Svensson Holm, Ann-Charlotte
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Berg, Cecilia
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Herbertsson, Helena
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Söderström, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Hammarström, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Lindström, Eva
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Bengtsson, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    5-Lipoxygenase activity is involved in platelet-induced fibroblast proliferation2006Conference paper (Refereed)
  • 39.
    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.

  • 40.
    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.

  • 41.
    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.

  • 42. 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.

  • 43.
    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.

  • 44.
    Li, Wei
    et al.
    Linköping University, Department of Medicine and Health Sciences, Clinical 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, Ximing
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Jonasson, Lena
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    7-beta-hydroxycholesterol induces natural killer cell death via oxidative lysosomal destalization.2009Conference paper (Refereed)
  • 45.
    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.

  • 46. 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.

  • 47.
    Herbertsson, Helena
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Kühme, Tobias
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Hammarström, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    A 12(S)-HETE receptor in Lewis lung carcinoma cells.1999In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, Vol. 447, 193-198 p.Article in journal (Other academic)
  • 48.
    Kurahashi, Yuko
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Herbertsson, Helena
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Söderström, Mats
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Rosenfeld, Michael G
    University of California, San Diego, La Jolla, CA, USA.
    Hammarström, Sven
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    A 12(S)-hydroxyeicosatetraenoic acid receptor interacts with steroid receptor coactivator-12000In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 97, no 11, 5779-5783 p.Article in journal (Refereed)
    Abstract [en]

    Lewis lung carcinoma cells contain specific high-affinity binding sites for the eicosanoid 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid [12(S)-HETE]. These binding sites have a cytosolic/nuclear localization and contain the heat shock proteins hsp70 and hsp90 as components of a high molecular weight cytosolic binding complex. The ligand binding subunit of this complex is a protein with an apparent molecular mass of ÿ50 kDa as judged by gel permeation chromatography. In this report, we present data showing that the 50-kDa 12(S)-HETE binding protein interacts as a homodimer with steroid receptor coactivator-1 (SRC-1) in the presence of 12(S)-HETE. Two putative interaction domains were mapped. One of these (amino acids 701-781) was within the nuclear receptor interaction domain in SRC-1 required for binding of various steroid and thyroid hormone receptors. It contains the most C-terminal of the three copies of LXXLL motif present in the nuclear receptor interaction domain. The second interaction domain was present in the N-terminal part of SRC-1 (amino acids 1-221). This region has two LXXLL motifs, one does not bind and the other binds only weakly to steroid and thyroid hormone receptors. Glutathione S-transferase (GST) pulldown experiments and far Western analyses demonstrated that the N-terminal region of SRC-1 (amino acids 1-212) alone does not bind the 50-kDa 12(S)-HETE binding protein, whereas GST/?SRC-11-1138 ligand-dependently pulled down a protein of ÿ50 kDa in size. Our results suggest that the 50-kDa 12(S)-HETE binding protein is a receptor that may signal through interaction with a nuclear receptor coactivator protein.

  • 49.
    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.

  • 50.
    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.

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