liu.seSök publikationer i DiVA
Ändra sökning
Avgränsa sökresultatet
12 1 - 50 av 58
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Johansson, Peter
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Coll, Norway.
    Alexander, Jan
    Norwegian Institute Public Heatlh, Norway; Norwegian University of Life Science NMBU, Norway.
    Wågsäter, Dick
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Significant changes in circulating microRNA by dietary supplementation of selenium and coenzyme Q10 in healthy elderly males. A subgroup analysis of a prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 4, artikel-id e0174880Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Selenium and coenzyme Q10 is essential for important cellular functions. A low selenium intake is reported from many European countries, and the endogenous coenzyme Q10 production is decreasing in the body with increasing age. Supplementation with selenium and coenzyme Q10 in elderly have shown reduced cardiovascular mortality and reduced levels of markers of inflammation. However, microRNA analyses could give important information on the mechanisms behind the clinical effects of supplementation. Methods Out of the 443 healthy elderly participants that were given supplementation with 200 mu g Se/ day as organic selenium yeast tablets, and 200 mg/day of coenzyme Q10 capsules, or placebo for 4 years, 25 participants from each group were randomized and evaluated regarding levels of microRNA. Isolation of RNA from plasma samples and quantitative PCR analysis were performed. Volcano- and principal component analyses (PCA)-plots were used to illustrate the differences in microRNA expression between the intervention, and the placebo groups. Serum selenium concentrations were measured before intervention. Findings On average 145 different microRNAs out of 172 were detected per sample. In the PCA plots two clusters could be identified indicating significant difference in microRNA expression between the two groups. The pre-treatment expression of the microRNAs did not differ between active treatment and the placebo groups. When comparing the post- treatment microRNAs in the active and the placebo groups, 70 microRNAs exhibited significant differences in expression, also after adjustment for multiple measurements. For the 20 microRNAs with the greatest difference in expression the difference was up to more than 4 fold and with a P-value that were less than 4.4e(-8). Conclusions Significant differences were found in expression of more than 100 different microRNAs with up to 4 fold differences as a result of the intervention of selenium and coenzyme Q10 combined. The changes in microRNA could be a part of mechanisms underlying the clinical effects earlier reported that reduced cardiovascular mortality, gave better cardiac function, and showed less signs of inflammation and oxdative stress following the intervention. However, more research is needed to understand biological mechanisms of the protective effects of selenium and Q10 supplementation.

  • 2.
    Aljabery, Firas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Aim: To study the possibility of detecting lymph node metastasis in locally advanced urinary bladder cancer (UBC) treated with radical cystectomy (RC) by using preoperative positron emission tomography/computed tomography (PET/CT) and peroperative sentinel node biopsy (SNB) technique. We also investigate the clinical significance of macrophage traits expression by cancer cells, M2-macrophage infiltration (MI) in tumor stroma and the immunohistochemical expression of biomarkers in cancer cells in relation to clinicopathologic data.

    Patients and Methods: We studied prospectively 122 patients with UBC, pathological stage pT1–pT4 treated with RC and pelvic lymph node dissection (PLND) during 2005–2011 at the Department of Urology, Linköping University Hospital. In the first study, we compared the results of preoperative PET/CT and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes (LNs). In the second study we investigated the value of SNB technique for detecting pathological LNs during RC in patients with UBC. W also examined the significance of the primary tumor location in the bladder in predicting the site of LN metastases, and the prognostic significance of lympho-vascular invasion (LVI) and lymph node metastasis density (LNMD) on survival. In the third study, we investigate the clinical significance of macrophage infiltration (MI) in tumor stroma and macrophage-traits expression by tumor cells. In the fourth study, we investigate the cell cycle suppression proteins p53, p21, pRb, p16, p14 ARF as well as tumors proliferative protein Ki67 and DNA repair protein ERCC1 expression in cancer cells. The results were compared with clinical and pathological characteristics and outcome.

    Results: Prior to RC, PET/CT was used to detect LN metastasis in 54 patients. PET/CT had 41% sensitivity, 86% specificity, 58% PPV, and 76% NPV, whereas the corresponding figures for conventional CT were 41%, 89%, 64%, and 77%. SNB was performed during RC in 103 patients. A median number of 29 (range 7–68) nodes per patient were examined. SNs were detected in 83 out of 103 patients (81%). The sensitivity and specificity for detecting metastatic disease by SNB varied among LN stations, with average values of 67% -90%. LNMD or ≥8% and LVI were significantly related to shorter survival. In 103 patients, MI was high in 33% of cases, while moderate and low infiltration occurred in 42% and 25% of tumors respectively. Patients with tumors containing high and moderate compared to low MI had low rate of LN metastases (P=0.06) and improved survival (P=0.06), although not at significant level. The expression of different tumor suppression proteins was altered in 47-91% of the patients. There were no significant association between cancer specific survival (CSS) and any of the studied biomarkers. In case of altered p14ARF, ERCC1 or p21, CSS was low in case of low p53 immunostaining but increased in case of p53 accumulation, although not at a significant level, indicating a possible protective effect of p53 accumulation in these cases.

    Conclusion: PET/ CT provided no improvement over conventional CT in detection and localization of regional LN metastases in bladder cancer. It is possible to detect the SN but the technique is not a reliable for perioperative localization of LN metastases; however, LVI and LNMD at a cut-off level of 8% had significant prognostic values. MI in the tumor microenvironment but not CD163 expression in tumor cells seems to be synergistic with the immune response against urinary bladder cancer. Our results further indicate that altered p53 might have protective effect on survival in case of altered p14ARF, p21, or ERCC1 indicating an interaction between these biomarkers.

    Delarbeten
    1. PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.
    Öppna denna publikation i ny flik eller fönster >>PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.
    Visa övriga...
    2015 (Engelska)Ingår i: BMC urology, ISSN 1471-2490, Vol. 15, nr 1, s. 87-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: We studied patients treated with radical cystectomy for locally advanced bladder cancer to compare the results of both preoperative positron emission tomography/computed tomography (PET/CT) and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes.

    METHODS: Patients who had bladder cancer and were candidates for cystectomy underwent preoperative PET/CT using 18-fluorodeoxyglucose (FDG) and conventional CT. The results regarding lymph node involvement were independently evaluated by two experienced radiologists and were subsequently compared with histopathology results, the latter of which were reassessed by an experienced uropathologist (HO).

    RESULTS: There were 54 evaluable patients (mean age 68 years, 47 [85 %] males and 7 [15 %] females) with pT and pN status as follows: < pT2-14 (26 %), pT2-10 (18 %), and > pT2-30 (56 %); pN0 37 (69 %) and pN+ 17 (31 %). PET/CT showed positive lymph nodes in 12 patients (22 %), and 7 of those cases were confirmed by histopathology; the corresponding results for conventional CT were 11 (20 %) and 7 patients (13 %), respectively. PET/CT had 41 % sensitivity, 86 % specificity, 58 % PPV, and 76 % NPV, whereas the corresponding figures for conventional CT were 41 %, 89 %, 64 %, and 77 %. Additional analyses of the right and left side of the body or in specified anatomical regions gave similar results.

    CONCLUSIONS: In this study, PET/CT and conventional CT had similar low sensitivity in detecting and localizing regional lymph node metastasis in bladder cancer.

    Nationell ämneskategori
    Urologi och njurmedicin Cancer och onkologi
    Identifikatorer
    urn:nbn:se:liu:diva-120796 (URN)10.1186/s12894-015-0080-z (DOI)000359832000001 ()26294219 (PubMedID)
    Tillgänglig från: 2015-08-25 Skapad: 2015-08-25 Senast uppdaterad: 2017-05-17
    2. Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study.
    Öppna denna publikation i ny flik eller fönster >>Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study.
    Visa övriga...
    2017 (Engelska)Ingår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 120, nr 3, s. 329-336Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    OBJECTIVES: To investigate the possibility of detecting sentinel lymph nodes (SNs) in patients with urinary bladder cancer (BCa) intra-operatively and whether the histopathological status of the identified SNs reflected that of the lymphatic field.

    PATIENTS AND METHODS: We studied 103 patients with BCa pathological stage T1-T4 who were treated with cystectomy and pelvic lymph node (LN) dissection during 2005-2011 at the Department of Urology, Linköping University Hospital. Radioactive tracer Nanocoll 70 MBq and blue dye were injected into the bladder wall around the primary tumour before surgery. SNs were detected ex vivo during the operation with a handheld Geiger probe (Gamma Detection System; Neoprobe Corp., Dublin, OH, USA). All LNs were formalin-fixed, sectioned three times, mounted on slides and stained with haematoxylin and eosin. An experienced uropathologist evaluated the slides.

    RESULTS: The mean age of the patients was 69 years, and 80 (77%) were male. Pathological staging was T1-12 (12%), T2-20 (19%), T3-48 (47%) and T4-23 (22%). A mean (range) number of 31 (7-68) nodes per patient were examined, totalling 3 253 nodes. LN metastases were found in 41 patients (40%). SNs were detected in 83 of the 103 patients (80%). Sensitivity and specificity for detecting metastatic disease by SN biopsy (SNB) varied between LN stations, with average values of 67% and 90%, respectively. LN metastatic density (LNMD) had a significant prognostic impact; a value of ≥8% was significantly related to shorter survival. Lymphovascular invasion (LVI) occurred in 65% of patients (n = 67) and was significantly associated with shorter cancer-specific survival (P < 0.001).

    CONCLUSION: We conclude that SNB is not a reliable technique for peri-operative localization of LN metastases during cystectomy for BCa; however, LNMD has a significant prognostic value in BCa and may be useful in the clinical context and in BCa oncological and surgical research. LVI was also found to be a prognostic factor.

    Ort, förlag, år, upplaga, sidor
    Wiley-Blackwell Publishing Inc., 2017
    Nyckelord
    #BladderCancer, #blcsm, cystectomy, lymph node metastasis, prognostic factors, sentinel node
    Nationell ämneskategori
    Kirurgi
    Identifikatorer
    urn:nbn:se:liu:diva-136947 (URN)10.1111/bju.13700 (DOI)000407781500011 ()27797436 (PubMedID)
    Anmärkning

    Funding agencies: County Council of Ostergotland, Linkoping, Sweden

    Tillgänglig från: 2017-05-01 Skapad: 2017-05-01 Senast uppdaterad: 2018-05-03
  • 3.
    Andelin, M.
    et al.
    Department of Medicine, NU Hospital Group, Uddevalla, Sweden..
    Kropff, J.
    Department of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands..
    Matuleviciene, V.
    Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    Joseph, J.I.
    Department of Anaesthesiology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA..
    Attvall, S.
    Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Hirsch, I.B.
    University of Washington, Seattle, WA, USA.
    Imberg, H.
    Statistiska Konsultgruppen, Gothenburg, Sweden..
    Dahlqvist, S.
    Department of Medicine, NU Hospital Group, Uddevalla, Sweden.
    Klonoff, D.
    Diabetes Research Institute, Mills-Peninsula Health Services, San Mateo, CA, USA..
    Haraldsson, B.
    Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    DeVries, J.H.
    Department of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands..
    Lind, M.
    Department of Medicine, NU Hospital Group, Uddevalla, Sweden Institute of Medicine, University of Gothenburg, Gothenburg, Sweden lind.marcus@telia.com..
    Assessing the Accuracy of Continuous Glucose Monitoring (CGM) Calibrated With Capillary Values Using Capillary or Venous Glucose Levels as a Reference.2016Ingår i: Journal of Diabetes Science and Technology, E-ISSN 1932-2968, Vol. 10, nr 4, s. 876-884Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Using the standard venous reference for the evaluation of continuous glucose monitoring (CGM) systems could possibly negatively affect measured CGM accuracy since CGM are generally calibrated with capillary glucose and venous and capillary glucose concentrations differ. We therefore aimed to quantify the effect of using capillary versus venous glucose reference samples on estimated accuracy in capillary calibrated CGM.less thanbr /greater thanMethods: We evaluated 41 individuals with type 1 diabetes mellitus (T1DM) using the Dexcom G4 CGM system over 6 days. Patients calibrated their CGM devices with capillary glucose by means of the HemoCue system. During 2 visits, capillary and venous samples were simultaneously measured by HemoCue and compared to concomitantly obtained CGM readings. The mean absolute relative difference (MARD) was calculated using capillary and venous reference samples.less thanbr /greater thanResults: Venous glucose values were 0.83 mmol/L (15.0 mg/dl) lower than capillary values over all glycemic ranges, P less than .0001. Below 4 mmol/l (72 mg/dl), the difference was 1.25 mmol/l (22.5 mg/dl), P = .0001, at 4-10 mmol/l (72-180 mg/dl), 0.67 mmol/l (12.0 mg/dl), P less than .0001 and above 10 mmol/l (180 mg/dl), 0.95 mmol/l (17.1 mg/dl), P less than .0001. MARD was 11.7% using capillary values as reference compared to 13.7% using venous samples, P = .037. Below 4 mmol/l (72 mg/dl) MARD was 16.6% and 31.8%, P = .048, at 4-10 mmol/l (72-180 mg/dl) 12.1% and 12.6%, P = .32, above 10 mmol/l (180 mg/dl) 8.7% and 9.2%, P = .82.less thanbr /greater thanConclusion: Using capillary glucose concentrations as reference to evaluate the accuracy of CGM calibrated with capillary samples is associated with a lower MARD than using venous glucose as the reference. Capillary glucose concentrations were significantly higher than venous in all glycemic ranges.less thanbr /greater than (© 2016 Diabetes Technology Society.)

  • 4.
    Barranco, Isabel
    et al.
    University of Murcia, Spain.
    Tvarijonaviciute, Asta
    University of Murcia, Spain.
    Perez-Patino, Cristina
    University of Murcia, Spain.
    Vicente Carrillo, Alejandro
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Parrilla, Inmaculada
    University of Murcia, Spain.
    Ceron, Jose J.
    University of Murcia, Spain.
    Martinez, Emilio A.
    University of Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Roca, Jordi
    University of Murcia, Spain.
    Glutathione Peroxidase 5 Is Expressed by the Entire Pig Male Genital Tract and Once in the Seminal Plasma Contributes to Sperm Survival and In Vivo Fertility2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 9, artikel-id e0162958Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Glutathione peroxidase-5 (GPX5) is an H2O2-scavenging enzyme identified in boar seminal plasma (SP). This study attempted to clarify its origin and role on sperm survival and fertility after artificial insemination (AI). GPX5 was expressed (Western blot and immunocytochemistry using a rabbit primary polyclonal antibody) in testes, epididymis and accessory sex glands (6 boars). SP-GPX5 concentration differed among boars (11 boars, P amp;lt; 0.001), among ejaculates within boar (44 ejaculates, P amp;lt; 0.001) and among portions within ejaculate (15 ejaculates). The first 10 mL of the spermrich fraction (SRF, sperm-peak portion) had a significantly lower concentration (8.87 +/- 0.78 ng/mL) than the rest of the SRF and the post-SRF (11.66 +/- 0.79 and 12.37 +/- 0.79 ng/mL, respectively, P amp;lt; 0.005). Spermmotility of liquid-stored semen AI-doses (n = 44, at 15-17 degrees C during 72h) declined faster in AI-doses with low concentrations of SP-GPX5 compared to those with high-levels. Boars (n = 11) with high SP-GPX5 showed higher farrowing rates and litter sizes than those with low SP-GPX5 (a total of 5,275 inseminated sows). In sum, GPX5 is widely expressed in the boar genital tract and its variable presence in SP shows a positive relationship with sperm quality and fertility outcomes of liquid-stored semen AI-doses.

  • 5.
    Claesson, Kjersti
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Faxälv, Lars
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Counting the platelets: a robust and sensitive quantification method for thrombus formation2016Ingår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 115, nr 6, s. 1178-1190Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Flow chambers are common tools used for studying thrombus formation in vitro. However, the use of such devices is not standardised and there is a large diversity among the flow chamber systems currently used, and also in the methods used for quantifying the thrombus development. It was the study objective to evaluate a new method for analysis and quantification of platelet thrombus formation that can facilitate comparison of results between research groups. Whole blood was drawn over a collagen patch in commercial Ibid or in-house constructed PDMS flow chambers. Five percent of the platelets were fluorescently labelled and z-stack time-lapse images were captured during thrombus formation. Images were processed in a Python script in which the number of platelets and their respective x-, y- and z-positions were obtained. For comparison with existing methods the platelets were also labelled and quantified using fluorescence intensity and thrombus volume estimations by confocal microscopy. The presented method was found less sensitive to microscope and image adjustments and provides more details on thrombus development dynamics than the methods for measuring fluorescence intensity and thrombus volume estimation. The platelet count method produced comparable results with commercial and PDMS flow chambers, and could also obtain information regarding the stability of each detected platelet in the thrombus. In conclusion, quantification of thrombus formation by platelet count is a sensitive and robust method that enables measurement of platelet accumulation and platelet stability in an absolute scale that could be used for comparisons between research groups.

  • 6.
    Dahlrot, R. H.
    et al.
    Odense Univ Hosp, Denmark.
    Dowsett, J.
    Odense Univ Hosp, Denmark.
    Fosmark, S.
    Odense Univ Hosp, Denmark.
    Malmström, Annika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, LAH Linköping.
    Henriksson, R.
    Umea Univ, Sweden; Reg Canc Ctr Stockholm Gotland, Sweden.
    Boldt, H.
    Odense Univ Hosp, Denmark.
    de Stricker, K.
    Odense Univ Hosp, Denmark.
    Sorensen, M. D.
    Odense Univ Hosp, Denmark; Univ Southern Denmark, Denmark.
    Poulsen, H. S.
    Rigshosp, Denmark.
    Lysiak, Malgorzata
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk genetik.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum.
    Hansen, S.
    Odense Univ Hosp, Denmark; Univ Southern Denmark, Denmark.
    Kristensen, B. W.
    Odense Univ Hosp, Denmark; Univ Southern Denmark, Denmark.
    Prognostic value of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression in glioblastoma excluding nontumour cells from the analysis2018Ingår i: Neuropathology and Applied Neurobiology, ISSN 0305-1846, E-ISSN 1365-2990, Vol. 44, nr 2, s. 172-184Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: It is important to predict response to treatment with temozolomide (TMZ) in glioblastoma (GBM) patients. Both MGMT protein expression and MGMT promoter methylation status have been reported to predict the response to TMZ. We investigated the prognostic value of quantified MGMT protein levels in tumour cells and the prognostic importance of combining information of MGMT protein level and MGMT promoter methylation status. Methods: MGMT protein expression was quantified in tumour cells in 171 GBMs from the population-based Region of Southern Denmark (RSD)cohort using a double immunofluorescence approach. Pyrosequencing was performed in 157 patients. For validation we used GBM-patients from a Nordic Study (NS) investigating the effect of radiotherapy and different TMZ schedules. Results: When divided at the median, patients with low expression of MGMT protein (AF-low) had the best prognosis (HR = 1.5, P = 0.01). Similar results were observed in the subgroup of patients receiving the Stupp regimen (HR = 2.0, P = 0.001). In the NS-cohort a trend towards superior survival (HR = 1.6, P = 0.08) was seen in patients with AF-low. Including MGMT promoter methylation status, we found for both cohorts that patients with methylated MGMT promoter and AF-low had the best outcome; median OS 23.1 and 20.0 months, respectively. Conclusion: Our data indicate that MGMT protein expression in tumour cells has an independent prognostic significance. Exclusion of nontumour cells contributed to a more exact analysis of tumour-specific MGMT protein expression. This should be incorporated in future studies evaluating MGMT status before potential integration into clinical practice.

  • 7.
    Danielsson, Olof
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    The Clinical and Pathological Spectrum of Idiopathic Inflammatory Myopathies: Implications for pathogenesis, classification and diagnosis2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background: Idiopathic inflammatory myopathies (IIM) constitute a heterogeneous group of diseases with severe consequences for the life of affected patients. Dermatomyositis, polymyositis and inclusion body myositis (IBM) are the classical representatives of this group. The treatments given today often have limited effects, and are taken at the cost of side effects. Major obstacles in the search for more effective treatments are; (1) an incomplete understanding of the disease mechanisms, (2) difficulties to delineate homogeneous disease groups for clinical studies and (3) the sometimes challenging task to diagnose these diseases.

    Aims: We addressed a number of “loose ends” in the areas of pathogenesis, classification and diagnosis; mechanisms of muscle fiber degeneration in IIM, with a focus of programmed cell death (apoptosis) and invasion of muscle  fibers by inflammatory cells (partial invasion); protecting and mediating factors present in muscle; the association of other diseases with IIM, in particular celiac disease ; the evaluation of two classification systems and laboratory methods for increased diagnostic performance.

    The studies: We included 106 patients, diagnosed at the Neuromuscular unit in Linköping, Sweden, with pathological muscle findings consistent with IIM. The incidence in the county of Östergötland (during 5 years) was 7.3 per million/year (3 patients each year). Of 88 patients with confirmed IIM 4 (4.5 %) had celiac disease, 33 (38%) had an associated systemic inflammatory disease and 5 (5.7 %) had a malignancy. Ninety-nine patients were included for a comparison of two classification systems using criteria of the European Neuromuscle Centre (Amato/ENMC), and the widely used Bohan and Peter classification, both with the addition of IBM according to Griggs et al. Using the Amato/ENMC criteria the most prevalent diagnostic group after IBM (30%) was nonspecific myositis (23%), followed by polymyositis (20%) and dermatomyositis 17%). A substantial number of patients meeting Bohan and Peter (or Griggs) criteria were excluded by Amato/ENMC criteria, most (21/23) due to lack of detectable muscle weakness. Extended muscle sectioning increased the sensitivity of a muscle biopsy by 15 % and the specificity by 22%, and showed an overlap between disease groups. Muscle biopsies from patients with IIM and controls were used to investigate pathological findings considered specific for disease groups, and for the presence of programmed cell death (apoptosis) and disease protecting and mediating factors in muscle. The presence of apoptotic muscle fiber nuclei was detected in muscle with partial invasion (however not in the invaded fibers) in the presence of granzyme B and CD8+ cytotoxic T cells. The major apoptosis inhibiting protein Bcl-2 was shown to be constitutionally expressed in healthy muscle but weakened in IIM.

    Conclusion: We present apoptosis as a possible disease mechanism in parallel with partial invasion of fibers. Furthermore, partial invasion may not be a suitable distinguishing feature in the pathogenesis, or for classification and diagnosis of IIM. We also introduce the anti-apoptotic Bcl-2 as a possible relevant muscle fiber protecting factor. A more extensive pathological work-up improves classification and diagnosis of IIM. The proposed Amato/ENMC creates a substantial portion of patients with non-specific or unclassified myositis. Associated diseases are common in IIM, and also include celiac disease.

    Delarbeten
    1. Classification and Diagnostic Investigation in Inflammatory Myopathies: A Study of 99 Patients
    Öppna denna publikation i ny flik eller fönster >>Classification and Diagnostic Investigation in Inflammatory Myopathies: A Study of 99 Patients
    2013 (Engelska)Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 40, nr 7, s. 1173-1182Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objective. Insights into the pathogenesis of inflammatory myopathies have led to new diagnostic methods. The aims of our study were (1) to evaluate the consequences of using the classification of Amato/European Neuromuscular Centre Workshop (ENMC), compared to that of Bohan and Peter; and (2) to evaluate any diagnostic benefit in using an extended pathological investigation. less thanbrgreater than less thanbrgreater thanMethods. From a consecutive retrospective database, we evaluated 99 patients for classification. Patients with inclusion body myositis (IBM) were classified according to Griggs, et al. In addition to routine stainings and immunohistochemistry, a multilevel serial sectioning procedure was performed on paraffin-embedded material, to identify scarce pathological findings. less thanbrgreater than less thanbrgreater thanResults. Classification according to Bohan and Peter could be performed for 83 of the 99 patients, whereas only 60 patients met the Amato/ENMC criteria, the latter resulting in the following diagnostic groups: IBM (n = 18), nonspecific myositis (n = 14), polymyositis (n = 12), dermatomyositis (n = 10), dermatomyositis sine dermatitis (n = 5), and immune-mediated necrotizing myopathy (n = 1). Most of the Amato/ENMC diagnostic groups harbored patients from several of the Bohan and Peter groups, which included a substantial group lacking proximal muscle weakness. The serial sectioning procedure was essential for classification of 9 patients (15%), and led to a more specific diagnosis for 13 patients (22%) according to Amato/ENMC. less thanbrgreater than less thanbrgreater thanConclusion. The classification of Amato/ENMC was more restrictive, forming groups based on clinical criteria and specified myopathological findings, which clearly differed from the groups of the Bohan and Peter classification. An extended pathological investigation increased the diagnostic yield of a muscle biopsy and highlights the quantity and specificity of certain pathological findings.

    Ort, förlag, år, upplaga, sidor
    Journal of Rheumatology, 2013
    Nyckelord
    INFLAMMATORY MYOPATHIES, IDIOPATHIC INFLAMMATORY MYOPATHIES, POLYMYOSITIS, DERMATOMYOSITIS, INCLUSION BODY MYOSITIS
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-96992 (URN)10.3899/jrheum.120804 (DOI)000321993800023 ()
    Anmärkning

    Funding Agencies|University Hospital Linkoping||County Council of Ostergotland||

    Tillgänglig från: 2013-09-02 Skapad: 2013-09-02 Senast uppdaterad: 2020-01-16
    2. Expression of apoptosis related proteins in normal and diseased muscle: A possible role for Bcl-2 in protection of striated muscle
    Öppna denna publikation i ny flik eller fönster >>Expression of apoptosis related proteins in normal and diseased muscle: A possible role for Bcl-2 in protection of striated muscle
    2009 (Engelska)Ingår i: NEUROMUSCULAR DISORDERS, ISSN 0960-8966, Vol. 19, nr 6, s. 412-417Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The unique absence of major histocompatibility complex class I antigen (MHC-I) expression in normal muscle is one possible mechanism protecting striated muscle. In order to define their possible involvement in protection of normal muscle. we investigated the expression of molecules involved in muscle fibre death and survival mechanisms (Bcl-2, Fas, Fas-ligand and TRAIL), focusing on disorders with possible involvement of cytotoxic T cells. We studied muscle biopsies from 20 healthy volunteers, from 10 patients affected by polymyositis and 10 by Duchenne muscular dystrophy. By using immunohistochemistry, Western blot and real-time PCR we detected a constitutional expression of Bcl-2 in healthy muscle, whereas the expression was weaker in disease processes. Fas-L and TRAIL were not detected in muscle fibres, and Fas only in muscle affected by disease. Our findings indicate that the major apoptotic protein Bcl-2 might have a hitherto unrecognized role in the protection of normal muscle.

    Nyckelord
    Inflammatory myopathy, Apoptosis, Bcl-2, TRAIL, Fas and Fas-L
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-19795 (URN)10.1016/j.nmd.2009.03.008 (DOI)
    Tillgänglig från: 2009-08-10 Skapad: 2009-08-10 Senast uppdaterad: 2020-01-16
  • 8.
    Edvardsson, Maria
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i Finspång.
    Circulating levels and assessment of clinical laboratory analytes, in >80-year-old, apparently healthy, moderately healthy, and frail individuals2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Blodprover används ofta för att undersöka ev förekomst av sjukdomar och för att fatta behandlingsbeslut. Vid tolkningen av resultaten används jämförelse antingen med tidigare värden från samma individ eller med en uppsättning lämpliga gruppbaserade referensintervall. Nuvarande referensintervall för vanliga laboratorieanalyter baseras ofta på mätningar från tillsynes friska personer i åldern 18–65 år. Åldern åtföljs av en allmän nedgång i organfunktioner och det är svårt att avgöra om en ev förändring av nivåerna av laboratorieanalyterna kan enbart beror på skillnaden i ålder, oberoende av miljö- eller sjukdomsprocesser. Skörhet kan ses som en konsekvens av åldersrelaterad multifaktoriell försämring - fysisk, kognitiv och sensorisk - vilket resulterar i sårbarhet och brist på anpassningsförmåga till interna stressfaktorer som infektion eller ny medicinering och/eller yttre stressorer, såsom att ramla hemma. Konsensus om definitionen av "skörhet" saknas, både nationellt och internationellt och frågan uppstod om olika definitioner av "skörhet" påverkar tolkningar och referensintervall för laboratorieanalyter, när man jämför olika grupper av äldre individer.

    Det övergripande syftet med avhandlingen var att tolka och bedöma cirkulerande nivåer för några kliniska laboratorieanalyser i förhållande till gällande referensvärden hos ≥80-åriga, ”hälsosamma”, ”måttligt friska” och ”sköra” individer.

    Data kommer från andra studier, inom vilka blodprov samlades, alla från individer ≥80 år. Jämförelser i studie I gjordes mellan blodprover från 138 individer i särskilt boende, med blodprover från referenspopulationer, både blodgivare och från NORIP-studien. Resultaten visade skillnader för vissa immunologiska (komplementfaktor 3 och 4) och kemiska analyser (alaninaminotransferas (Alat), fosfat, albumin, natrium, kreatinin och urea), men inte alla (aspartataminotransferas (Asat), gamma-glytamyltransferas (γ-GT) eller laktatdehydrgenas (LD)). Det var oklart om skillnaderna berodde på skillnader i ålder mellan de äldre och referenspopulationerna eller om de äldre individerna hade kroniska sjukdomar och medicinerade. I studie II klassificerades 569 individer >80 år som ”hälsosamma”, ”måttligt friska” och ”sköra”, baserat på sjukdomar, medicinering och fysiska och kognitiva förmågor. Statistiska skillnader mellan grupperna hittades för de undersökta analyterna: albumin, Alat, Asat, kreatinin och y-GT. I studie IV delades individer från papper II (n = 569) in i två grupper och delades därefter upp i "hälsosamma", "måttligt friska" och "sköra". En grupp delades in i ”hälsosamma”, ”måttligt friska” och ”sköra” baserat på fysiska och kognitiva förmågor och den andra gruppen delades in baserat på skörhetsindex. Det fanns ingen statistisk skillnad mellan ”hälsosamma” och ”måttligt friska” grupperna, oavsett vilken klassificeringsmodell som användes. Bland ”sköra” individer inträffade skillnader i nivåer för tre av de fem undersökta analyterna: Alat, kreatinin och γ-GT, med lägre nivåer där skörhetsindex hade använts som klassificeringsmodell jämfört klassificering baserad på fysiska och kognitiva förmågor. Syftet med studie III var att studera om 1-års förändringar i blodstatusparametrar (hemoglobin (Hb), erytrocytpartikelkoncentration (EPK), erytrocytvolymfraktion (EVF), medelcellvolym (MCV), mean corpuscular Hb concentration (MCHC), leukocytpartikelkoncentration (LPK) och trombocytpartikelkoncentration (TPK)), C-reaktivt protein (CRP) och interleukin (IL)-1β, IL-1Ra, IL-6, IL-8 och IL-10 var associerade med överlevnad hos individer från särskilt boende > 80 år. De mest framträdande resultaten var att förhöjda nivåer av CRP och IL-8 under 1-års uppföljning var förknippade med förkortad överlevnadstid hos äldre från särskilt boende. Baserat på den aktuella avhandlingen är det tydligt att det finns behov av referensintervall som beaktar både ålder och hälsostatus hos äldre individer. En rimlig slutsats när man tolkar nivåer av laboratorieanalyter hos äldre individer med sjukdom eller skörhet är att individuell utvärdering baserad på individens tidigare nivåer rekommenderas.

    Delarbeten
    1. Clinical use of conventional reference intervals in the frail elderly
    Öppna denna publikation i ny flik eller fönster >>Clinical use of conventional reference intervals in the frail elderly
    Visa övriga...
    2015 (Engelska)Ingår i: Journal of Evaluation In Clinical Practice, ISSN 1356-1294, E-ISSN 1365-2753, Vol. 21, nr 2, s. 229-235Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Rationale, aims and objectives

    Reference intervals provided by the laboratory are commonly established by measuring samples from apparently healthy subjects in the ages 18–65 years, excluding elderly individuals with chronic diseases and medication. The aim of our study was to establish whether current reference intervals for immune parameters and chemical biomarkers are valid for older individuals including those with chronic diseases, so-called frail elderly.

    Methods

    Data from our cohort of 138 non-infected nursing home residents (NHR), mean age 86.8 years, range 80–98, were compared with raw data, as basis for the development of reference intervals, obtained from reference populations, like blood donors (IgA, IgG, IgM, C3 and C4) and from the Nordic Reference Interval Project (NORIP) (alanine aminotransferase, albumin, aspartate aminotransferase, creatinine, gamma-glutamyl transferase, lactate dehydrogenase, phosphate, sodium and urea). Immune parameters were measured by nephelometry and in NORIP the measurements were performed by means of different routine methods, in more than 100 laboratories.

    Results

    Only nine individuals (7%) of NHR were found to be free from chronic disease. C3, C4 (P < 0.001) and IgG levels (P < 0.05) were higher, while IgM levels (P < 0.001) were lower in NHR compared with reference blood donors. Levels of alanine aminotransferase, phosphate (P < 0.001), albumin (P < 0.05) and sodium (P < 0.01) were lower while creatinine and urea levels were higher (P < 0.001) in NHR compared with NORIP subjects.

    Conclusion

    Comparing laboratory results from elderly people with conventional reference intervals can be misleading or even dangerous, as normal conditions may appear pathological, or vice versa and thus lead to unnecessary or even harmful treatment.

    Nyckelord
    ageing; biomarker; clinical practice; nursing home resident
    Nationell ämneskategori
    Annan klinisk medicin
    Identifikatorer
    urn:nbn:se:liu:diva-117172 (URN)10.1111/jep.12294 (DOI)000351871200009 ()25494854 (PubMedID)
    Tillgänglig från: 2015-04-21 Skapad: 2015-04-21 Senast uppdaterad: 2020-01-16
    2. Differences in levels of albumin, ALT, AST, gamma-GT and creatinine in frail, moderately healthy and healthy elderly individuals
    Öppna denna publikation i ny flik eller fönster >>Differences in levels of albumin, ALT, AST, gamma-GT and creatinine in frail, moderately healthy and healthy elderly individuals
    Visa övriga...
    2018 (Engelska)Ingår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 56, nr 3, s. 471-478Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Reference intervals are widely used as decision tools, providing the physician with information about whether the analyte values indicate ongoing disease process. Reference intervals are generally based on individuals without diagnosed diseases or use of medication, which often excludes elderly. The aim of the study was to assess levels of albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine and gamma-glutamyl transferase (gamma-GT) in frail, moderately healthy and healthy elderly indivuduals. Methods: Blood samples were collected from individuals amp;gt; 80 years old, nursing home residents, in the Elderly in Linkoping Screening Assessment and Nordic Reference Interval Project, a total of 569 individuals. They were divided into three cohorts: frail, moderately healthy and healthy, depending on cognitive and physical function. Albumin, ALT, AST, creatinine and gamma-GT were analyzed using routine methods. Results: Linear regression predicted factors for 34% of the variance in albumin were activities of daily living (ADL), gender, stroke and cancer. ADLs, gender and weight explained 15% of changes in ALT. For AST levels, ADLs, cancer and analgesics explained 5% of changes. Kidney disease, gender, Mini Mental State Examination (MMSE) and chronic obstructive pulmonary disease explained 25% of the variation in creatinine levels and MMSE explained three per cent of gamma-GT variation. Conclusions: Because a group of people are at the same age, they should not be assessed the same way. To interpret results of laboratory tests in elderly is a complex task, where reference intervals are one part, but far from the only one, to take into consideration.

    Ort, förlag, år, upplaga, sidor
    WALTER DE GRUYTER GMBH, 2018
    Nyckelord
    aging; analyte; clinical interpretation; frail; reference interval
    Nationell ämneskategori
    Klinisk laboratoriemedicin
    Identifikatorer
    urn:nbn:se:liu:diva-145114 (URN)10.1515/cclm-2017-0311 (DOI)000423681100022 ()28988219 (PubMedID)
    Anmärkning

    Funding Agencies|Landstinget i Ostergotland Sverige [LIO-359661]

    Tillgänglig från: 2018-02-12 Skapad: 2018-02-12 Senast uppdaterad: 2019-09-09
    3. Elevated levels of CRP and IL-8 are related to reduce survival time: 1-year follow-up measurements of different analytes in frail elderly nursing home residents
    Öppna denna publikation i ny flik eller fönster >>Elevated levels of CRP and IL-8 are related to reduce survival time: 1-year follow-up measurements of different analytes in frail elderly nursing home residents
    Visa övriga...
    2019 (Engelska)Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 79, nr 5, s. 288-292Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    There are only few studies with specific focus on predictors of survival in nursing home residents (NHRs). The aim was to study whether 1-year changes in complete blood count (including hemoglobin, red blood cells, erythrocyte volume fraction, mean corpuscular volume, mean corpuscular hemoglobin concentration, white blood cells count and platelet count), C-reactive protein and interleukin-1 beta (IL-1 beta), IL-1Ra, IL-6, IL-8 and IL-10, are associated with 8-year survival in elderly NHRs, aged amp;gt;= 80 years. Complete blood count, C-reactive protein and interleukins were measured at baseline, after 6 and 12 months from 167 NHRs aged 80-101 years, mean age 88 +/- 4.5 years, 75% of whom were women. Dates of death were collected from the National Death Register 8 years after baseline. Levels of hemoglobin, red blood cells and mean corpuscular hemoglobin concentration were lower after 1-year, but higher for mean corpuscular volume and IL-1 beta, compared to baseline or 6 month follow-up. In the Cox regression model with a time-dependent covariate, raised levels of C-reactive protein and IL-8 were associated with reduced survival time. Elevated levels of C-reactive protein and IL-8 during 1-year follow-up were related to reduce lengths of survival in elderly NHRs.

    Ort, förlag, år, upplaga, sidor
    TAYLOR & FRANCIS LTD, 2019
    Nyckelord
    Aging; frailty; blood cell count; c-reactive protein; interleukins; survival
    Nationell ämneskategori
    Hematologi
    Identifikatorer
    urn:nbn:se:liu:diva-158342 (URN)10.1080/00365513.2019.1609695 (DOI)000469576100001 ()31074311 (PubMedID)
    Anmärkning

    Funding Agencies|Research Council of Southeast Sweden; Futurum County Council of Jonkoping, Sweden

    Tillgänglig från: 2019-06-28 Skapad: 2019-06-28 Senast uppdaterad: 2020-01-16
  • 9.
    Edvardsson, Maria
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i Finspång, Vårdcentralen Finspång.
    Sund-Levander, Märtha
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Milberg, Anna
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i östra Östergötland, Palliativt kompetenscentrum.
    Wressle, Ewa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken.
    Marcusson, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken.
    Grodzinsky, Ewa
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Division of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Sweden.
    Differences in levels of albumin, ALT, AST, gamma-GT and creatinine in frail, moderately healthy and healthy elderly individuals2018Ingår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 56, nr 3, s. 471-478Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Reference intervals are widely used as decision tools, providing the physician with information about whether the analyte values indicate ongoing disease process. Reference intervals are generally based on individuals without diagnosed diseases or use of medication, which often excludes elderly. The aim of the study was to assess levels of albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine and gamma-glutamyl transferase (gamma-GT) in frail, moderately healthy and healthy elderly indivuduals. Methods: Blood samples were collected from individuals amp;gt; 80 years old, nursing home residents, in the Elderly in Linkoping Screening Assessment and Nordic Reference Interval Project, a total of 569 individuals. They were divided into three cohorts: frail, moderately healthy and healthy, depending on cognitive and physical function. Albumin, ALT, AST, creatinine and gamma-GT were analyzed using routine methods. Results: Linear regression predicted factors for 34% of the variance in albumin were activities of daily living (ADL), gender, stroke and cancer. ADLs, gender and weight explained 15% of changes in ALT. For AST levels, ADLs, cancer and analgesics explained 5% of changes. Kidney disease, gender, Mini Mental State Examination (MMSE) and chronic obstructive pulmonary disease explained 25% of the variation in creatinine levels and MMSE explained three per cent of gamma-GT variation. Conclusions: Because a group of people are at the same age, they should not be assessed the same way. To interpret results of laboratory tests in elderly is a complex task, where reference intervals are one part, but far from the only one, to take into consideration.

  • 10.
    Falkeborn, Tina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Asahara, Naomi
    Advanced Medical Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Japan.
    Hayashi, Masayuki
    Advanced Medical Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Japan.
    Arai, Masaaki
    Advanced Medical Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Japan.
    Hinkula, Jorma
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Maltais, Anna-Karin
    Eurocine Vaccines AB, Karolinska Institutet Science Park, Solna, Sweden.
    Comparison of the mucosal adjuvant Endocine™ with two well-known adjuvants: cholera toxin and alum2015Ingår i: Jacobs Journal of Vaccine and Vaccination, ISSN 2381-2664, Vol. 1, nr 1, artikel-id 006Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To enable efficient mucosal vaccination with split or subunit antigens, an adjuvant is often needed. To date, no mucosal adjuvants are approved for human use, however, there are a variety of mucosal adjuvants in development, including the liposome-based adjuvant Endocine™. The aim of this study was to evaluate split influenza antigens together with Endocine™ and in order to assess the potency of Endocine™, the induction of humoral immune responses were compared to those following influenza vaccination with cholera toxin (CT) or aluminum salt (alum). We show that Endocine™ significantly enhances influenza-specific immune responses in intranasally immunized mice compared to nonadjuvanted vaccine. Furthermore, vaccines adjuvanted with Endocine™ evoked comparable serum IgG and virus neutralizing (VN) antibody titers as nasal vaccines adjuvanted with CT. Compared to parenteral vaccination with alum, Endocine™ triggered significantly higher mucosal and serum IgA titers, and similar VN titers. Taken together, these results support further development of Endocine™ as a mucosal adjuvant and as part of a nasal influenza vaccine candidate.

  • 11.
    Falkeborn, Tina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Hinkula, Jorma
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Lindberg, Alf
    Eurocine Vaccines AB, Karolinska Institutet Science Park, Solna, Sweden.
    Maltais, Anna-Karin
    Eurocine Vaccines AB, Karolinska Institutet Science Park, Solna, Sweden.
    The mucosal adjuvant 1 Endocine™ increases immune responses to influenza antigen in aged miceManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    More effective influenza vaccines for the elderly population is needed. The vaccines used today are less effective in elderly compared to in adults. It is more difficult to stimulate a protective immune response in elderly due to immunosenescence. Elderly people have a decline in both humoral and cell mediated immunity, which make them more susceptible to viral infections. The aim of this study was to evaluate the mucosal adjuvant Endocine™ together with split influenza antigen in different ages of BALB/c mice (15, 20 and 25 months old). The results from this study show that a nasal influenza vaccine  formulated with Endocine™ enhanced both systemic and mucosal immune responses compared to an unadjuvanted vaccine delivered subcutaneously or intra nasal in aged mice. However, in the 25 months old mice only a very modest immune response was detected. Although the influenza-specific immune responses in aged mice were not induced to the same levels as achieved in young mice, the results show that nasal vaccine formulated with Endocine™ could provide benefits for the elderly.

  • 12.
    Grankvist, Kjell
    et al.
    Institutionen för medicinsk biovetenskap, Umeå universitet.
    Hammarsten, Ola
    Avdelningen för Laboratoriemedicin vid Institutionen för biomedicin, Göteborgs universitet.
    Maria, Berggren Söderlund
    Region Kronoberg, Klinisk kemi och transfusionsmedicin.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Laboratoriernas verksamhet2018Ingår i: Laurells klinisk kemi i praktisk medicin / [ed] Elvar Theodorsson, Maria Berggren Söderlund, Lund: Studentlitteratur AB, 2018, 10, s. 13-30Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 13.
    Greaves, Ronda F
    et al.
    School of Health and Biomedical Sciences, RMIT University, Bundoora, Australia.
    Smith, Janet M
    Beastall, Graham
    Laboratory Medicine Consulting, Glasgow, UK.
    Florkowski, Chris
    Clinical Biochemistry Unit, Canterbury Health Laboratories, Christchurch, New Zealand.
    Langman, Loralie
    Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, United States.
    Sheldon, Joanna
    Protein Reference Unit, St. George’s Hospital, London, UK.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    The IFCC Curriculum - phase 1.2018Ingår i: EJIFCC, ISSN 1650-3414, Vol. 29, nr 1, s. 55-93Artikel i tidskrift (Refereegranskat)
  • 14.
    Haglund, Felix
    et al.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Garvin, Stina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Ihre-Lundgren, Catharina
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Nilsson, Inga-Lena
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Hall, Evelina
    Karolinska University Hospital, Sweden.
    Carling, Tobias
    Yale School Med, CT USA.
    Hoog, Anders
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Christofer Juhlin, C.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Detailed Lymph Node Sectioning of Papillary Thyroid Carcinoma Specimen Increases the Number of pN1a Patients2016Ingår i: Endocrine pathology, ISSN 1046-3976, E-ISSN 1559-0097, Vol. 27, nr 4, s. 346-351Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Papillary thyroid carcinoma (PTC) is a common endocrine malignancy, frequently presenting with lymph node metastasis at the time of diagnosis. Lymph node staging (N) partly determines treatment, follow-up, and prognosis. Since 2011, our institution has employed a more comprehensive histopathological work-up of lymph nodes in patients with PTC. We sought to retrospectively determine the value of serial lymph node level sectioning in PTCs with negative preoperative lymph node status (pN0) as a method to increase the sensitivity of detecting metastatic disease. We included all patients that underwent thyroidectomy and central neck dissection and subsequent comprehensive lymph node level sectioning due to PTC with an initial pN0 status between the years 2011 and 2015 at our institution. Sixty-seven cases of PTC with a median of 10 metastatic free lymph nodes identified per case were included. After serial lymph node sectioning of the central compartment, 11 cases (16 %) revealed lymph node metastasis, six of which (55 %) presented with a small primary tumor (amp;lt; 20 mm, T1). Of all T1 tumors with initial pN0 status, 18 % (T1a) and 9 % (T1b) reached a pN1 stage after comprehensive lymph node sectioning. Cases with altered lymph node status had a median of 15 identified lymph nodes as compared to ten in cases that remained negative. We conclude that comprehensive lymph node sectioning increased the sensitivity of detecting metastases in PTC and altered the pathological TNM staging (pTNM) for a significant number of patients. Although of limited prognostic significance, the method should be considered as an adjunct tool when assessing lymph node status of PTC as a part of the routine histological work-up to ensure an accurate cancer staging.

  • 15.
    Hammarsten, Ola
    et al.
    Avdelningen för Laboratoriemedicin vid Institutionen för biomedicin, Göteborgs universitet.
    Grankvist, Kjell
    Institutionen för medicinsk biovetenskap, Umeå universitet.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Tolkning av analysresultat2018Ingår i: Laurells klinisk kemi i praktisk medicin / [ed] Elvar Theodorsson, Maria Berggren Söderlund, Lund: Studentlitteratur AB, 2018, 10, s. 31-54Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 16.
    Hedbrant, Johan
    Linköpings universitet, Institutionen för ekonomisk och industriell utveckling, Mekanisk värmeteori och strömningslära. Linköpings universitet, Tekniska fakulteten.
    [Common sense against rolls of fat--should we reduce our intake of carbohydrates?].: Folkvett mot fettvalk – bör vi minska vårt kolhydratintag?2003Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 100, nr 47, s. 3889-3890Artikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Västvärldens kostexperter har utifrån ett primitivt energibalanstänkande lanserat budskapet att äta kolhydrater, som är mindre energitäta än fett och borde ge lägre energiintag. Istället har man råkat öka aptiten eftersom kosten innehållit mindre andel protein, samt ökat kroppsfettmassan då ökat kolhydratintag medfört ökade insulinhalter och fettinlagring samt blockerad fettförbränning.

  • 17.
    Hillarp, Andreas
    et al.
    Halland Cty Hosp, Sweden.
    Strandberg, Karin
    Univ and Reg Labs Reg Skane, Sweden.
    Baghaei, Fariba
    Sahlgrens Univ Hosp, Sweden.
    Blixter, Inger Fagerberg
    Univ Gothenburg, Sweden.
    Gustafsson, Kerstin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Effects of the oral, direct factor Xa inhibitor edoxaban on routine coagulation assays, lupus anticoagulant and anti-Xa assays2018Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 78, nr 7-8, s. 575-583Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Edoxaban is an oral direct factor Xa inhibitor for prophylaxis and treatment of thromboembolic disorders. The effects on common coagulation assays are clinically valuable information and in certain clinical situations a quick assessment of the anticoagulant is wanted. Our aim was to investigate the effect of edoxaban on routine coagulation methods and evaluate anti-Xa assays, commonly used for other direct factor Xa inhibitors, for estimation of the drug concentration. Edoxaban was spiked to plasma samples from healthy subjects in the concentration range 0-742 mu g/L and analyzed using different reagents for activated partial thromboplastin time (APTT) and prothrombin time (PT). Assays for antithrombin, activated protein C resistance, lupus anticoagulant (LA) and chromogenic anti-Xa assays were also included. Edoxaban displayed similar effects in vitro to other oral direct Xa inhibitors. The concentration needed to double the coagulation time varied between assays and reagents; 539-758 mu g/L for the APTT and between 329 and 2505 mu g/L for the PT. Edoxaban gave false high antithrombin activities in assays based on Xa-inhibition. Two integrated assays for LA, both based on activation with dilute Russells viper venom, displayed different results. Chromogenic anti-Xa assays displayed linear dose-response curves with edoxaban up to approximately 500 mu g/L. In conclusion, therapeutic concentrations of edoxaban variably affect different coagulation assays, and even different reagents within an assay group. In comparison with other oral Xa-inhibitors, the in vitro effects of edoxaban were more similar to rivaroxaban than apixaban. For measurement of edoxaban concentration in plasma, it is possible to use the chromogenic anti-Xa assays.

  • 18.
    Holm, Angelika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Aquaporins in Infection and Inflammation2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The ability of eukaryotic cells to change their shape and to migrate directionally is highly dependent on active volume regulation in cells building up tissues as well as in individual cells. Transmembrane fluxes of water via specialized water channels, called aquaporins (AQPs), facilitate the changes of volume and shape, which additionally require a complex interplay between the plasma membrane and the cytoskeleton. AQPs have been shown to be involved in the development of inflammatory processes and diseases. The aims of the studies underlying this thesis were to further elucidate the expression and function of AQPs in both bacterial and viral infections as well as in the inflammatory disease, microscopic colitis. For this, molecular techniques qPCR, immunoblotting and live, holographic, confocal and super-resolution imaging were used.

    When cells of the innate immune system encounter pathogens they need to respond and prepare for migration and phagocytosis and do so through volume regulatory processes. The Gramnegative bacterium Pseudomonas aeruginosa utilizes a small molecule-based communication system, called quorum sensing (QS) to control the production of its virulence factors and biofilms. We found that P. aeruginosa with a complete QS system elicits a stronger phagocytic response in human blood-derived macrophages compared to its lasI-/rhlI- mutant lacking the production of the QS molecules N-butyryl-L-homoserine lactone (C4-HSL) and N-3-oxododecanoyl-L-homoserine lactone (3O-C12-HSL). Infection with P. aeruginosa further increases the expression of AQP9 and induces re-localisation of AQP9 to the front and trailing ends of macrophages. Moreover, the 3O-C12-HSL alone elevates the expression of AQP9, redistribute the water channel to the front and rear ends and increases the cell area and volume of macrophages. Both infection with the wild type P. aeruginosa and the treatment with 3OC12-HSL change the nano-structural architecture of the AQP9 distribution in macrophages.

    Viruses use the intracellular machinery of the invaded cells to produce and assemble new viral bodies. Intracellular AQPs are localised in a membranes of cellular organelles to regulate their function and morphology. C3H10T1/2 fibroblasts transiently expressing green fluorescent protein (GFP)-AQP6 show a reduced expression of AQP6 after Hazara virus infection and an increased cell area. Overexpressing AQP6 in C3H10T1/2 cells reduces the infectivity of Hazara virus indicating that AQP6 expression has a protective role in virus infections.

    Ion and water channels in the epithelial cell lining tightly regulate the water homeostasis. In microscopic colitis (MC), patients suffer from severe watery diarrhoeas. For the first time, we have shown that the expression of AQP1, 8 and 11 and the sodium/hydrogen exchanger NHE1 are reduced in colonic biopsies from MC patients compared to healthy control individuals. Following treatment with the glucocorticoid budesonide the patients experienced a rapid recovery and we observed a restored or increased expression of the AQPs and NHE1 during treatment, suggesting a role for AQPs in the diarrhoeal mechanisms in MC.

    Taken together, this thesis provides new evidence on the importance of water homeostasis regulation through AQPs during infections and inflammation and opens up a door for further investigations of roles for AQPs in inflammatory processes.

    Delarbeten
    1. Pseudomonas aeruginosa lasI/rhlI quorum sensing genes promote phagocytosis and aquaporin 9 redistribution to the leading and trailing regions in macrophages
    Öppna denna publikation i ny flik eller fönster >>Pseudomonas aeruginosa lasI/rhlI quorum sensing genes promote phagocytosis and aquaporin 9 redistribution to the leading and trailing regions in macrophages
    2015 (Engelska)Ingår i: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 6, nr 915Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Pseudomonas aeruginosa controls production of its multiple virulence factors and biofilm development via the quorum sensing (QS) system. QS signals also interact with and affect the behavior of eukaryotic cells. Host water homeostasis and aquaporins (AQP) are essential during pathological conditions since they interfere with the cell cytoskeleton and signaling, and hereby affect cell morphology and functions. We investigated the contribution of F? aeruginosa QS genes lasl/rhIl to phagocytosis, cell morphology, AQP9 expression, and distribution in human macrophages, using immunoblotting, confocal, and nanoscale imaging. Wild type F? aeruginosa with a functional QS system was a more attractive prey for macrophages than the lasl/rhIl mutant lacking the production of QS molecules, 30-C-12-HSL, and C-4 -HSL, and associated virulence factors. The F? aeruginosa infections resulted in elevated AQP9 expression and relocalization to the leading and trailing regions in macrophages, increased cell area and length; bacteria with a functional QS system lasl/rhIl achieved stronger responses. We present evidence for a new role of water fluxes via AQP9 during bacteria macrophage interaction and for the QS system as an important stimulus in this process. These novel events in the interplay between F? aeruginosa and macrophages may influence on the outcome of infection, inflammation, and development of disease.

    Ort, förlag, år, upplaga, sidor
    FRONTIERS MEDIA SA, 2015
    Nyckelord
    host-bacteria relationship; quorum sensing; N-acylhomoserine lactone; innate immunity; macrophage; water homeostasis; aquaporin
    Nationell ämneskategori
    Klinisk medicin
    Identifikatorer
    urn:nbn:se:liu:diva-122056 (URN)10.3389/fmicb.2015.00915 (DOI)000360626200001 ()26388857 (PubMedID)
    Anmärkning

    Funding Agencies|Swedish Research Council [2010-3045]; European Science foundation (TraPPs Euromembrane project); Euro-BioImaging Proof-of Concept Studies; Magnus Bergvalls Foundation; Faculty of Health Sciences, Linkoping University

    Tillgänglig från: 2015-12-18 Skapad: 2015-10-19 Senast uppdaterad: 2017-12-01
    2. Pseudomonas aeruginosa N-3-oxo-dodecanoyl-homoserine Lactone Elicits Changes in Cell Volume, Morphology, and AQP9 Characteristics in Macrophages
    Öppna denna publikation i ny flik eller fönster >>Pseudomonas aeruginosa N-3-oxo-dodecanoyl-homoserine Lactone Elicits Changes in Cell Volume, Morphology, and AQP9 Characteristics in Macrophages
    2016 (Engelska)Ingår i: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, ISSN 2235-2988, Vol. 6, nr 32Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Quorum sensing (QS) communication allows Pseudomonas aeruginosa to collectively control its population density and the production of biofilms and virulence factors. QS signal molecules, like N-3-oxo-dodecanoyl-L-homoserine lactone (30-C-12-HSL), can also affect the behavior of host cells, e.g., by modulating the chemotaxis, migration, and phagocytosis of human leukocytes. Moreover, host water homeostasis and water channels aquaporins (AQP) are critical for cell morphology and functions as AQP interact indirectly with the cell cytoskeleton and signaling cascades. Here, we investigated how P aeruginosa 30-C-12-HSL affects cell morphology, area, volume and AQP9 expression and distribution in human primary macrophages, using quantitative PCR, immunoblotting, two- and three-dimensional live imaging, confocal and nanoscale imaging. Thus, 30-C-12-HSL enhanced cell volume and area and induced cell shape and protrusion fluctuations in macrophages, processes tentatively driven by fluxes of water across cell membrane through AQP9, the predominant AQP in macrophages. Moreover, 30-C-12-HSL upregulated the expression of AQP9 at both the protein and mRNA levels. This was accompanied with enhanced whole cell AQP9 fluorescent intensity and redistribution of AQP9 to the leading and trailing regions, in parallel with increased cell area in the macrophages. Finally, nanoscopy imaging provided details on AQP9 dynamics and architecture within the lamellipodial area of 30-C-12-HSL-stimulated cells. We suggest that these novel events in the interaction between P aeruginosa and macrophage may have an impact on the effectiveness of innate immune cells to fight bacteria, and thereby resolve the early stages of infections and inflammations.

    Ort, förlag, år, upplaga, sidor
    FRONTIERS MEDIA SA, 2016
    Nyckelord
    host-bacteria interactions; quorum sensing; N-acylhomoserinelactone; innate immunity; macrophage; water homeostasis; aquaporin
    Nationell ämneskategori
    Klinisk medicin
    Identifikatorer
    urn:nbn:se:liu:diva-127262 (URN)10.3389/fcimb.2016.00032 (DOI)000372710500001 ()27047801 (PubMedID)
    Anmärkning

    Funding Agencies|Swedish Research Council [2010-3045]; European Science foundation (TraPPs Euromembrane project); Magnus Bergvall Foundation; Faculty of Medicine and Health Sciences, Linkoping University

    Tillgänglig från: 2016-04-20 Skapad: 2016-04-19 Senast uppdaterad: 2018-05-14
    3. Protective role of host aquaporin 6 against Hazara virus, a model for Crimean–Congo hemorrhagic fever virus infection
    Öppna denna publikation i ny flik eller fönster >>Protective role of host aquaporin 6 against Hazara virus, a model for Crimean–Congo hemorrhagic fever virus infection
    Visa övriga...
    2016 (Engelska)Ingår i: FEMS Microbiology Letters, ISSN 0378-1097, E-ISSN 1574-6968, Vol. 363, nr 8, artikel-id fnw058Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Crimean–Congo hemorrhagic fever virus (CCHFV) is an arthropod-borne pathogen that causes infectious disease with severe hemorrhagic manifestations in vascular system in humans. The proper function of the cells in the vascular system is critically regulated by aquaporins (AQP), water channels that facilitate fluxes of water and small solutes across membranes. With Hazara virus as a model for CCHFV, we investigated the effects of viruses on AQP6 and the impact of AQP6 on virus infectivity in host cells, using transiently expressed GFP-AQP6 cells, immunofluorescent assay for virus detection, epifluorescent imaging of living cells and confocal microscopy. In GFP-AQP6 expressing cells, Hazara virus reduced both the cellular and perinuclear AQP6 distribution and changed the cell area. Infection of human cell with CCHFV strain IbAR 10200 downregulated AQP6 expression at mRNA level. Interestingly, the overexpression of AQP6 in host cells decreased the infectivity of Hazara virus, speaking for a protective role of AQP6. We suggest the possibility for AQP6 being a novel player in the virus–host interactions, which may lead to less severe outcomes of an infection.

    Ort, förlag, år, upplaga, sidor
    Oxford University Press, 2016
    Nyckelord
    Host–virus interactions; Nairovirus; Crimean–Congo hemorrhagic fever virus; aquaporin; virus infectivity; water homeostasis
    Nationell ämneskategori
    Cell- och molekylärbiologi Mikrobiologi inom det medicinska området
    Identifikatorer
    urn:nbn:se:liu:diva-127499 (URN)10.1093/femsle/fnw058 (DOI)000377970600013 ()26976854 (PubMedID)
    Forskningsfinansiär
    Vetenskapsrådet, 2010-3045European Science Foundation (ESF)Magnus Bergvalls StiftelseVetenskapsrådet, 214–7495Linköpings universitet
    Anmärkning

    Funding agencies: Swedish Research Council [2010-3045]; European Science foundation; Magnus Bergvall Foundation; Faculty of Medicine and Health Sciences, Linkoping University; Infect-ERA Second Call (Swedish Research Council) [214-7495]

    Tillgänglig från: 2016-04-28 Skapad: 2016-04-28 Senast uppdaterad: 2018-01-10Bibliografiskt granskad
  • 19.
    Håkansson, Irene
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken i Linköping.
    Ernerudh, Jan
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Vrethem, Magnus
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Neurologiska kliniken i Linköping.
    Dahle, Charlotte
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Ekdahl, Kristina N.
    Centre of Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden ; Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
    Complement activation in cerebrospinal fluid in clinically isolated syndrome and early stages of relapsing remitting multiple sclerosis2020Ingår i: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 340, artikel-id 577147Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To assess if markers of complement activation are associated with disease activity, C1q, C3, C3a and sC5b-9 levels in plasma and cerebrospinal fluid (CSF) were determined in 41 patients with clinically isolated syndrome (CIS) or remitting multiple sclerosis (RRMS), in a prospective longitudinal four-year cohort study. C1q in CSF (CSF-C1q) was significantly higher in patients than in controls. Baseline CSF-C1q and CSF-C3a correlated with several neuroinflammatory markers and neurofilament light chain levels. Baseline CSF-C3a correlated with the number of T2 lesions at baseline and new T2 lesions during follow-up. Baseline CSF-C3a was also significantly higher in patients with (n = 21) than in patients without (n = 20) signs of disease activity according to the NEDA-3 concept during one year of follow-up (p ≀ .01) Study results support that complement activation is involved in MS pathophysiology and that CSF-C3a carries prognostic information.

  • 20.
    Jacobsson, Stefan
    et al.
    Avdelningen för Klinisk kemi och transfusionsmedicin, Institutionen för biomedicin, Sahlgrenska akademin, Göteborgs universitet.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Anemier2018Ingår i: Laurells klinisk kemi i praktisk medicin / [ed] Elvar Theodorsson, Maria Berggren Söderlund, Lund: Studentlitteratur AB, 2018, 10, s. 209-264Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 21.
    Järemo, Petter
    et al.
    Östergötlands Läns Landsting, Närsjukvården i östra Östergötland, Medicinkliniken ViN. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Eriksson-Franzen, Marie
    Region Östergötland, Närsjukvården i östra Östergötland, Medicinkliniken ViN.
    Milovanovic, Micha
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Hälsa, Aktivitet, Vård (HAV). Linköpings universitet, Medicinska fakulteten. Östergötlands Läns Landsting, Närsjukvården i östra Östergötland, Medicinkliniken ViN.
    Platelets, gender and acute cerebral infarction2015Ingår i: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, ISSN ISSN 1479-5876, Vol. 13, nr 267Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    Platelets may well be significant in the pathogenesis of cerebral infarction. Platelets vary substantially according to gender. The scope of our current work is to establish if female and male stroke sufferers differ regarding platelet reactivity.

    Patients and methods

    73 Consecutive individuals stricken by acute ischemic cerebral infarction (31 females, 42 males) participated. All stroke subtypes were included. Platelet counts was determined electronically. Platelet reactivity i.e. the presence of surface-bound fibrinogen following provocation was analyzed with a flow cytometer. ADP (1.7 μmol/L) and a thrombin receptor agonist (TRAP-6) (57 μmol/L) were the agonists used.

    Results

    Female stroke sufferers had higher platelet counts (p = 0.013) but their platelets were less reactive. The p values were (p = 0.038) and (p = 0.016) for ADP and TRAP-6, respectively.

    Conclusion

    The current study demonstrates that women suffering acute cerebral infarction have less reactive platelets. It is concluded that gender affects platelets. Our study indicates that it may be beneficial to individualize platelet inhibition of stroke sufferers according to gender.

  • 22.
    Kallner, Anders
    et al.
    Karolinska Univ Hosp, Sweden.
    Petersmann, Astrid
    Univ Med, Germany; Univ Med, Germany.
    Nauck, Matthias
    Univ Med, Germany.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Measurement repeatability profiles of eight frequently requested measurands in clinical chemistry determined by duplicate measurements of patient samples2020Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Measurement uncertainties in clinical chemistry are commonly regarded as heteroscedastic - having a constant relative standard deviation irrespective of the concentration of the measurand. The uncertainty is usually determined at two concentrations using stabilized control materials and assumed to represent the analytical goal. The purpose of the present study was to use duplicates of unselected patient samples to calculate the absolute and relative repeatability component of the intra-laboratory measurement uncertainty from duplicates, using the Dahlberg formula and analysis of variance components. Estimates were made at five different concentration intervals of ALT, AST, Calcium, Cholesterol, Creatinine, CRP, Triglycerides and TSH covering the entire concentration interval of the patient cohort. This partioning allows detailing their repeatability profiles. The calculations of the profiles were based on randomly selected results from sets of duplicates ranging from 12,000 to 65,000 pairs. The repeatability of the measurands showed substantial variability within the measuring interval. Therefore, characterizing imprecision profiles as purely homo- or heteroscedastic or by a single number may not be optimal for the intended use. The present data make a case for nuancing the evaluation of analytical goals and minimal differences of measurement results by establishing uncertainty profiles under repeatability conditions, using natural patient samples.

  • 23.
    Kallner, Anders
    et al.
    Karolinska Univ Hosp, Sweden.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    An experimental study of methods for the analysis of variance components in the inference of laboratory information2020Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Measurement uncertainty (MU) can be estimated and calculated by different procedures, representing different aspects and intended use. It is appropriate to distinguish between uncertainty determined under repeatability and reproducibility conditions, and to distinguish causes of variation using analysis of variance components. The intra-laboratory MU is frequently determined by repeated measurements of control material(s) of one or several concentrations during a prolonged period of time. We demonstrate, based on experimental results, how such results can be used to identify the repeatability, pure reproducibility and intra-laboratory variance as the sum of the two. Native patient material was used to establish repeatability using the Dahlberg formula for random differences between measurements and an expanded Dahlberg formula if a non-random difference, e.g. bias, was expected. Repeatability and reproducibility have different clinical relevance in intensive care compared to monitoring treatment of chronic diseases, comparison with reference intervals or screening.

  • 24.
    Kallner, Anders
    et al.
    Karolinska Univ Hosp, Sweden.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Repeatability imprecision from analysis of duplicates of patient samples and control materials2020Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Measurement imprecision is usually calculated from measurement results of the same stabilized control material(s) obtained over time, and is therefore, principally, only valid at the concentration(s) of the selected control material(s). The resulting uncertainty has been obtained under reproducibility conditions and corresponds to the conventional analytical goals. Furthermore, the commutability of the control materials used determines whether the imprecision calculated from the control materials reflects the imprecision of measuring patient samples. Imprecision estimated by measurements of patient samples uses fully commutable samples, freely available in the laboratories. It is commonly performed by calculating the results of routine patient samples measured twice each. Since the duplicates are usually analysed throughout the entire concentration interval of the patient samples processed in the laboratory, the result will be a weighted average of the repeatability imprecision measured in the chosen measurement intervals or throughout the entire interval of concentrations encountered in patient care. In contrast, the uncertainty derived from many measurements of control materials over periods of weeks is usually made under reproducibility conditions. Consequently, the repeatability and reproducibility imprecision play different roles in the inference of results in clinical medicine. The purpose of the present review is to detail the properties of the imprecision calculated by duplicates of natural samples, to explain how it differs from imprecision calculated from single concentrations of control materials, and to elucidate what precautions need to be taken in case of bias, e.g. due to carry-over effects.

  • 25.
    Lewin, Nongnit
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Ryhov Hosp, Sweden.
    Luetragoon, Thitiya
    Ryhov Hosp, Sweden; Naresuan Univ, Thailand.
    Andersson, Bengt-Åke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Ryhov Hosp, Sweden.
    Oliva, Delmy
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Ryhov Hosp, Sweden.
    Nilsson, Mats
    Ryhov Hosp, Sweden.
    Strandeus, Michael
    Ryhov Hosp, Sweden.
    Lofgren, Sture
    Ryhov Hosp, Sweden.
    Rutqvist, Lars-Erik
    Swedish Match AB, Sweden.
    Lewin, Freddi
    Ryhov Hosp, Sweden.
    The Influence of Single Nucleotide Polymorphisms and Adjuvant Radiotherapy on Systemic Inflammatory Proteins, Chemokines and Cytokines of Patients With Breast Cancer2019Ingår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 39, nr 3, s. 1287-1292Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Independently of tumour and treatment modulation, the host immune response status plays an important role in the clinical outcome of patients with cancer. The influence of single nucleotide polymorphisms (SNPs) and adjuvant radiotherapy (RT) on the systemic immune response status of patients with breast cancer was investigated. Materials and Methods: Eighty-six female patients recovering from breast cancer surgery were investigated. As a control cohort, 82 healthy female blood donors were used. Blood-based SNPs, plasma C-reactive protein (CRP), cytokines and chemokines were analyzed for this purpose. Results: Independently of tumour stage and hormone receptor status, dysregulation of plasma CRP, chemokine (C-C motif) ligand 4 (CCL4) and interleukin 2 (IL2), but not CCL5, CCL2, platelet-derived growth factor, IL6, IL10, IL12, interferon-gamma or tumour necrosis factor alpha were detected in the patients when compared to controls. The extent of alteration in plasma levels of CRP and IL2 patients was significantly associated with SNPs in CRP rs1800947 and IL2 rs6822844, respectively. These SNPs had no influence on the levels of corresponding plasma biomarkers in the healthy controls. Adjuvant RT reduced plasma CRP and CCL5 levels in patients with regards to CRP rs1800947CC, CCL5 rs2107538GG and CCL5 rs2280789AA sequences. Conclusion: Dysregulation of immune responses, as indicated by plasma levels of CRP, CCL4 and IL2 were found in patients with breast cancer despite the removal of the tumour mass. The benefit of adjuvant RT, as indicated by reduced plasma amounts of inflammatory protein CRP and chemokine CCL5 were based on the SNPs of the patients. Analyses of blood-based SNPs, plasma CRP, IL2 and CCL5 are low cost, rapid and can be carried out using general laboratory facilities while requiring only a peripheral blood sample. The possibility of using these blood-based biomarkers as an indicator of patient immune status for selection of individual patient treatment warrants further investigation.

  • 26.
    Lieberman, L.
    et al.
    University of Health Network, Canada.
    Devine, D. V.
    Canadian Blood Serv, Canada; University of British Columbia, Canada,.
    Reesink, H. W.
    University of Amsterdam, Netherlands.
    Panzer, S.
    Medical University of Vienna, Austria.
    Wong, J.
    Australian Red Cross Blood Serv, Australia.
    Raison, T.
    Australian Red Cross Blood Serv, Australia.
    Benson, S.
    Australian Red Cross Blood Serv, Australia.
    Pink, J.
    Australian Red Cross Blood Serv, Australia.
    Leitner, G. C.
    University of Vienna, Austria.
    Horvath, M.
    University of Vienna, Austria.
    Compernolle, V.
    Belgian Red Cross Flanders, Belgium.
    Prado Scuracchio, P. S.
    Blood Bank Hospital Sirio Libanes, Brazil.
    Wendel, S.
    Blood Bank Hospital Sirio Libanes, Brazil.
    Delage, G.
    Hema Quebec, Canada.
    Nahirniak, S.
    Alberta Health Serv, Canada.
    Dongfu, X.
    Shanghai Blood Centre, Peoples R China.
    Krusius, T.
    Finnish Red Cross Blood Serv, Finland.
    Juvonen, E.
    Finnish Red Cross Blood Serv, Finland.
    Sainio, S.
    Finnish Red Cross Blood Serv, Finland.
    Cazenave, J. -P.
    Etab Francais Sang EFS Alsace, France.
    Guntz, P.
    Etab Francais Sang EFS Alsace, France.
    Kientz, D.
    Etab Francais Sang EFS Alsace, France.
    Andreu, G.
    Institute National Transfus Sanguine INTS, France.
    Morel, P.
    EFS Bourgogne Franche Comte, France.
    Seifried, E.
    German Red Cross, Germany.
    Hourfar, K.
    German Red Cross, Germany.
    Lin, C. K.
    Hong Kong.
    O'Riordan, J.
    National Blood Centre, Ireland.
    Raspollini, E.
    Fdn Ca Granda Osped Maggiore Policlin, Italy.
    Villa, S.
    Fdn Ca Granda Osped Maggiore Policlin, Italy.
    Rebulla, P.
    Fdn Ca Granda Osped Maggiore Policlin, Italy; Fdn Ca Granda Osped Maggiore Policlin, Italy.
    Flanagan, P.
    New Zealand Blood Serv, New Zealand.
    Teo, D.
    Health Science Author, Singapore.
    Lam, S.
    Health Science Author, Singapore.
    Ang, A. L.
    Health Science Author, Singapore.
    Lozano, M.
    University of Clin Hospital, Spain.
    Sauleda, S.
    Blood and Tissue Bank Catalonia, Spain.
    Cid, J.
    University of Clin Hospital, Spain.
    Pereira, A.
    University of Clin Hospital, Spain.
    Ekermo, Bengt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Niederhauser, C.
    Blood Transfus Serv SRC Berne, Switzerland.
    Waldvogel, S.
    Blood Transfus Serv SRC, Switzerland.
    Fontana, S.
    Blood Transfus Serv SRC Berne, Switzerland.
    Desborough, M. J.
    John Radcliffe Hospital, England.
    Pawson, R.
    John Radcliffe Hospital, England.
    Li, M.
    Blood Syst Inc, AZ, USA.
    Kamel, H.
    Blood Syst Inc, AZ, USA.
    Busch, M.
    Blood Syst Inc, AZ, USA.
    Qu, L.
    University of Pittsburgh, PA, USA; Institute Transfus Med, PA, USA.
    Triulzi, D.
    University of Pittsburgh, PA, USA; Institute Transfus Med, PA, USA.
    Prevention of transfusion-transmitted cytomegalovirus (CMV) infection: Standards of care2014Ingår i: Vox Sanguinis, ISSN 0042-9007, E-ISSN 1423-0410, Vol. 107, nr 3, s. 276-311Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    n/a

  • 27.
    Lindberg, Ulrika
    et al.
    Lund Univ, Sweden.
    Svensson, Lisbeth
    Lund Univ, Sweden.
    Hellmark, Thomas
    Lund Univ, Sweden.
    Segelmark, Mårten
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Njurmedicinska kliniken US.
    Shannon, Oonagh
    Lund Univ, Sweden.
    Increased platelet activation occurs in cystic fibrosis patients and correlates to clinical status2018Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 162, s. 32-37Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cystic fibrosis (CF) is an inflammatory lung disease. Platelets have an emerging role in inflammation, however previous studies of platelet activation in CF have generated conflicting results. In this study, we determined platelet function in CF patients and correlated platelet activation to establish clinical and laboratory parameters. Twenty-two patients, aged 20.7 to 54.4 (mean 34.0, SD 9.45) years and with a mean FEV1% pred (forced expiratory volume in one second, % of predicted) of 72 (SD 21.4, range 32-110) were recruited. A combination of platelet assays was used: platelet aggregation, platelet activation and platelet-leukocyte complex formation. Platelets from CF patients exhibited significantly increased aggregation when stimulated ex-vivo, a tendency towards increased platelet upregulation of CD62P, but no increase of GPIIb/IIIa activation (PAC-1). Platelet-monocyte complex (PMC) formation was significantly increased in CF patients compared to controls, while platelet-neutrophil complex formation was not. In the CF group, platelet aggregation correlates with levels of anti-neutrophil cytoplasmic antibodies (ANCA) with specificity for bactericidal/permeability-increasing protein (BPI), BPI-ANCA (r = 0.56). The formation of PMCs correlates with lung function decline (1-FEV1%), CRP and BPI-ANCA (r = 0.61, 0.55, 0.5). We therefore confirm the presence of increased platelet activation in CF patients, and determine that further evaluation of platelet activation in relation to prognostic factors in CF is warranted.

  • 28.
    Loftås, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken ViN.
    Response to neoadjuvant treatment in rectal cancer surgery2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Rectal cancer is one of the three most common malignancies in Sweden with an annual incidence of about 2000 cases. Current treatment consists of surgical resection of the rectum including the loco-regional lymph nodes in the mesorectum. In advanced cases, neoadjuvant chemo-radiotherapy (CRT) prior to the operative treatment reduces local recurrences and enables surgery. The neoadjuvant treatment can also eradicate the tumour completely, i.e. complete response. This research project was designed to investigate the effects of preoperative radiotherapy/ CRT and analyze methods to predict response to CRT.

    Study I investigated the expression of the FXYD-3 protein with immunohistochemistry in rectal cancer, with or without preoperative radiotherapy. The results from the total cohort showed that, strong FXYD-3 expression was correlated to infiltrative tumour growth (p = 0.02). In the radiotherapy group, strong FXYD-3 expression was related to an unfavourable prognosis (p = 0.02). Tumours with strong FXYD-3 expression had less tumour necrosis (p = 0.02) after radiotherapy. FXYD-3 expression in the primary tumour was increased compared to normal mucosa (p=0.008). We concluded that FXYD-3 expression was a prognostic factor in patients receiving preoperative radiotherapy for rectal cancer.

    Study II investigated FXYD-3 expression in tumours that developed local recurrences following surgery and compared this with expression in tumours that did not develop local recurrences. There was no difference in the expression of FXYD-3 between the group that developed local recurrences and the group that did not develop local recurrences. There was no difference in survival between those with strong or weak FXYD-3 expression. We concluded that this study could not confirm the findings from study 1 i.e. that FXYD-3 expression has prognostic significance in rectal cancer.

    Study III was a register-based study on the incidence and effects of complete response to neoadjuvant treatment. Eight per cent of the patients with adequate CRT to achieve complete response also had a complete histological response of the luminal tumor in the resected bowel. Sixteen per cent of that group had remaining lymph node metastases in the operative specimen. Chemotherapy together with radiotherapy doubled the chance of complete response in the luminal tumour. Patients with remaining lymph node metastases had a lower survival rate compared to those without. We concluded that residual nodal involvement after neoadjuvant treatment was an important factor for reduced survival after complete response in the luminal tumour.

    Study IV followed up the results from the previous study by re-evaluating magnetic resonance imaging (MRI)- images in patients with complete tumour response. Two experienced MRI radiologists performed blinded re-staging of post CRT MR- images from patients with complete response in the luminal tumour. One group with lymph node metastases and another one without were studied and the results compared with the pathology reports. The sensitivity, specificity, and positive and negative predicted values for correct staging of positive lymph nodes was 37%, 84%, 70% and 57%. The size of the largest lymph node (4.5 mm, p=0.04) seemed to indicate presence of a tumour positive lymph node. We concluded that MRI couldn’t correctly stage patients for lymph node metastases in patients with complete response to CRT in the luminal tumour.

    Delarbeten
    1. EXPRESSION OF FXYD-3 IS AN INDEPENDENT PROGNOSTIC FACTOR IN RECTAL CANCER PATIENTS WITH PREOPERATIVE RADIOTHERAPY
    Öppna denna publikation i ny flik eller fönster >>EXPRESSION OF FXYD-3 IS AN INDEPENDENT PROGNOSTIC FACTOR IN RECTAL CANCER PATIENTS WITH PREOPERATIVE RADIOTHERAPY
    Visa övriga...
    2009 (Engelska)Ingår i: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, ISSN 0360-3016, Vol. 75, nr 1, s. 137-142Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Purpose: FXYD-3 (MAT-8) is overexpressed in several types of cancers; however, its clinical relevance in rectal cancers has not been studied. Therefore, we examined FXYD-3 expression in rectal cancers from the patients who participated in a Swedish clinical trial of preoperative radiotherapy (RT) to determine whether FXYD-3 was overexpressed in rectal cancers and correlated with RT, survival, and other clinicopathologic variables. Methods and Materials: The study included 140 rectal cancer patients who participated in a clinical trial of preoperative RT, 65 with and 75 without RT before surgery. FXYD-3 expression was immumohistochemically examined in distant (n = 70) and adjacent (n = 101) normal mucosa, primary tumors (n = 140), and lymph node metastasis (n = 36). Results: In the whole cohort, strong FXYD-3 expression was correlated with infiltrative tumor growth (p = 0.02). In the RT group, strong FXYD-3 expression alone (p = 0.02) or combined with phosphatase of regenerating liver was associated with an unfavorable prognosis (p = 0.02), independent of both TNM stage and tumor differentiation. In tumors with strong FXYD-3 expression, there was less tumor necrosis (p = 0.02) and a trend toward increased incidence of distant metastasis (p = 0.08) after RT. None of these effects was seen in the non-RT group. FXYD-3 expression in the primary tumors tended to he increased compared with normal mucosa regardless of RT. Conclusion: FXYD-3 expression was a prognostic factor independent of tumor stage and differentiation in patients receiving preoperative RT for rectal cancer.

    Nyckelord
    FXYD-3, Rectal cancer, Radiotherapy, Prognosis, Immunohistochemistry
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-20598 (URN)10.1016/j.ijrobp.2008.10.076 (DOI)
    Tillgänglig från: 2009-09-16 Skapad: 2009-09-15 Senast uppdaterad: 2016-11-24
    2. FXYD-3 expression in relation to local recurrence of rectal cancer
    Öppna denna publikation i ny flik eller fönster >>FXYD-3 expression in relation to local recurrence of rectal cancer
    Visa övriga...
    2016 (Engelska)Ingår i: Radiation Oncology Journal, ISSN 2234-1900, Vol. 34, nr 1, s. 52-58Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Purpose: In a previous study, the transmembrane protein FXYD-3 was suggested as a biomarker for a lower survival rate and reduced radiosensitivity in rectal cancer patients receiving preoperative radiotherapy. The purpose of preoperative irradiation in rectal cancer is to reduce local recurrence. The aim of this study was to investigate the potential role of FXYD-3 as a biomarker for increased risk for local recurrence of rectal cancer.

    Materials and Methods: FXYD-3 expression was immunohistochemically examined in surgical specimens from a cohort of patients with rectal cancer who developed local recurrence (n = 48). The cohort was compared to a matched control group without recurrence (n = 81).

    Results: Weak FXYD-3 expression was found in 106/129 (82%) of the rectal tumors and strong expression in 23/129 (18%). There was no difference in the expression of FXYD-3 between the patients with local recurrence and the control group. Furthermore there was no difference in FXYD-3 expression and time to diagnosis of local recurrence between patients who received preoperative radiotherapy and those without.

    Conclusion: Previous findings indicated that FXYD-3 expression may be used as a marker of decreased sensitivity to radiotherapy or even overall survival. We were unable to confirm this in a cohort of rectal cancer patients who developed local recurrence.

    Ort, förlag, år, upplaga, sidor
    Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea, 2016
    Nyckelord
    Rectal cancer, Human FXYD3 protein, Local recurrence
    Nationell ämneskategori
    Radiologi och bildbehandling Cancer och onkologi
    Identifikatorer
    urn:nbn:se:liu:diva-132758 (URN)10.3857/roj.2016.34.1.52 (DOI)27104167 (PubMedID)
    Tillgänglig från: 2016-11-23 Skapad: 2016-11-23 Senast uppdaterad: 2016-12-07Bibliografiskt granskad
    3. Nodal involvement in luminal complete response after neoadjuvant treatment for rectal cancer
    Öppna denna publikation i ny flik eller fönster >>Nodal involvement in luminal complete response after neoadjuvant treatment for rectal cancer
    2016 (Engelska)Ingår i: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 42, nr 6, s. 801-807Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Pathological complete response (pCR) after neoadjuvant therapy in rectal cancer is correlated with improved survival. There is limited knowledge on the incidence of pCR at a national level with uniform guidelines. The aim of this prospective register-based study was to investigate the incidence and outcome of pCR in relation to neoadjuvant therapy in a national cohort. Method: All patients abdominally operated for rectal cancer between 2007 and 2012 (n = 7885) were selected from The Swedish Colorectal Cancer Register. Twenty-six per cent (n = 2063) had neoadjuvant therapy with either long or short course radiotherapy with amp;gt;4 weeks delay with the potential to achieve pCR. The primary endpoints were pCR and survival in relation to neoadjuvant therapy. Results: Complete eradication of the luminal tumor, ypTO was found in 161 patients (8%). In 83% of the ypTO the regional lymph nodes were tumor negative (ypTONO), 12% had 1-3 positive lymph nodes (ypTON1) and 4% had more than three positive lymph nodes (ypTON2). There was significantly greater survival with ypTO compared to ypT+ (hazard ratio 0.38 (C.I 0.25-0.58)) and survival was significantly greater in patients with ypTONO compared to ypT0N1-2 (hazard ratio 0.36 (C.I 0.15-0.86)). In ypTO, cT3-4 tumors had the greater risk of node-positivity. The added use of chemotherapy resulted in 10% ypTO compared to 5.1% in the group without chemotherapy (p amp;lt; 0.00004). Conclusion: Luminal pathological complete response occurred in 8%, 16% of them had tumor positive nodes. The survival benefit of luminal complete response is dependent upon nodal involvement status. (C) 2016 Elsevier Ltd. All rights reserved.

    Ort, förlag, år, upplaga, sidor
    ELSEVIER SCI LTD, 2016
    Nyckelord
    Rectal cancer; Complete response; Lymph nodes; Neoadjuvant treatment
    Nationell ämneskategori
    Cancer och onkologi
    Identifikatorer
    urn:nbn:se:liu:diva-130432 (URN)10.1016/j.ejso.2016.03.013 (DOI)000379559300007 ()27146960 (PubMedID)
    Tillgänglig från: 2016-08-07 Skapad: 2016-08-05 Senast uppdaterad: 2017-05-02
  • 29.
    Lundin, Anna-Carin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Tendinosis in Trigger Finger2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Trigger finger is one of the most common hand conditions, with a prevalence of almost 3%. The aetiology remains unclear even though many causes have been suggested. The prevailing paradigm is that the pathogenesis of trigger finger is ascribed to primary changes in the first fibrous condensation of the tendon sheath (A1-pulley). Several studies have investigated pathology in the pulley, but few have investigated the tendon. The general aim of this thesis was to find out if there is pathology in the trigger finger tendon and to define it.

    We first looked at trigger finger tendon biopsies in a light microscope, and found that they were histologically different from healthy tendons. They showed signs of micro-ruptures, collagen degradation, increased amounts of ground substance, both hyper- and hypo-cellular areas, round active cell nuclei and absence of inflammatory cells, all similar to tendinosis. The histological picture was further assessed by using a scoring system for Achilles tendinosis. The trigger finger tendons scored high, suggesting a similar histopathology.

    Next, we performed a quantitative real-time polymerase chain reaction (qPCR) on trigger finger tendons. We assessed the mRNA expression of 10 genes, which have been described to be differently expressed in Achilles tendinosis (collagen 1 and 3, versican, decorin, biglycan, aggrecan, MMP-2, MMP-3, ADAMTS-5, and TIMP-3). The overall expression pattern agreed with previous studies on Achilles tendinosis, suggesting that the cellular function in trigger finger tendons is disturbed in a similar way as in Achilles tendinosis.

    Recent experimental and observational research has suggested potential side effects of statin treatment on tendons, but firm evidence was lacking. We performed an epidemiological study on two large population-based cohorts. Statin use was found to increase the risk of both trigger finger and tendinosis in the shoulder and Achilles tendons, especially among men. This suggests a similar pathology in trigger finger and tendinosis.

    We have also studied the time to treatment effect after a single injection of glucocorticoid in trigger finger. Our results suggest that 60-80% of patients can expect resolution of the triggering within 14 days, and half of them within seven days. This result allows correct information to be given to the patient and proper planning of follow-ups.

    In conclusion, the pathology in trigger finger tendons is similar to tendinosis in other tendons.

    Delarbeten
    1. Trigger finger and tendinosis
    Öppna denna publikation i ny flik eller fönster >>Trigger finger and tendinosis
    2012 (Engelska)Ingår i: Journal of Hand Surgery, European Volume, ISSN 1753-1934, E-ISSN 2043-6289, Vol. 37, nr 3, s. 233-236Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The pathogenesis of trigger finger has generally been ascribed to primary changes in the pulley. Histological examination of the affected tendons has rarely been done. We studied biopsies from tendons of trigger fingers from 29 patients and compared these to biopsies from six intact tendons. We used a modified Movin score, which describes the tendinosis of the Achilles tendon. Trigger finger tendons had a high score (14.2; SD, 2.2) consistent with tendinosis, while the controls were almost normal (2.5; SD, 1.9). This suggests that the tendon is also affected, and that trigger finger is a form of tendinosis.

    Ort, förlag, år, upplaga, sidor
    Sage Publications, 2012
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-76086 (URN)10.1177/1753193411421853 (DOI)000300994100007 ()21987275 (PubMedID)
    Tillgänglig från: 2012-03-26 Skapad: 2012-03-26 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
    2. Trigger finger, tendinosis, and intratendinous gene expression
    Öppna denna publikation i ny flik eller fönster >>Trigger finger, tendinosis, and intratendinous gene expression
    2014 (Engelska)Ingår i: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 24, nr 2, s. 363-368Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The pathogenesis of trigger finger has generally been ascribed to primary changes in the first annular ligament. In contrast, we recently found histological changes in the tendons, similar to the findings in Achilles tendinosis or tendinopathy. We therefore hypothesized that trigger finger tendons would show differences in gene expression in comparison to normal tendons in a pattern similar to what is published for Achilles tendinosis. We performed quantitative real-time polymerase chain reaction on biopsies from finger flexor tendons, 13 trigger fingers and 13 apparently healthy control tendons, to assess the expression of 10 genes which have been described to be differently expressed in tendinosis (collagen type 1a1, collagen 3a1, MMP-2, MMP-3, ADAMTS-5, TIMP-3, aggrecan, biglycan, decorin, and versican). In trigger finger tendons, collagen types 1a1 and 3a1, aggrecan and biglycan were all up-regulated, and MMP-3and TIMP-3 were down-regulated. These changes were statistically significant and have been previously described for Achilles tendinosis. The remaining four genes were not significantly altered. The changes in gene expression support the hypothesis that trigger finger is a form of tendinosis. Because trigger finger is a common condition, often treated surgically, it could provide opportunities for clinical research on tendinosis.

    Ort, förlag, år, upplaga, sidor
    Wiley, 2014
    Nyckelord
    tendinopathy; tendinosis; stenosing tendovaginitis; tendovaginitis stenosans; quantitative real-time PCR; qPCR
    Nationell ämneskategori
    Ortopedi Cell- och molekylärbiologi
    Identifikatorer
    urn:nbn:se:liu:diva-106131 (URN)10.1111/j.1600-0838.2012.01514.x (DOI)000332982700018 ()
    Tillgänglig från: 2014-04-25 Skapad: 2014-04-24 Senast uppdaterad: 2018-01-11
  • 30.
    Löwbeer, Christian
    et al.
    Aleris Medilab och Institutionen för laboratoriemedicin, Avdelningen för klinisk kemi, Karolinska institutet, Stockholm.
    Hammarsten, Ola
    Avdelningen för Laboratoriemedicin vid Institutionen för biomedicin, Sahlgrenska universitetssjukhuset, Göteborgs universitet.
    Rönnelid, Johan
    Institutionen för immunologi, genetik och patologi, Klinisk immunologi, Uppsala universitet.
    Ridefelt, Peter
    Institutionen för medicinska vetenskaper, Klinisk kemi, Uppsala universitet.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Energiomsättning, diabetes och lipoproteinrubbningar2018Ingår i: Laurells klinisk kemi i praktisk medicin / [ed] Elvar Theodorsson, Maria Berggren Söderlund, Lund: Studentlitteratur AB, 2018, 10, s. 345-414Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 31.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Tillförlitliga referensintervall krävs för värdering av P-ALP: Nya pediatriska referensintervall för alkaliskt fosfatas har klinisk betydelse för att hitta rätt till diagnosen2017Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, nr 42, s. 1750-1751, artikel-id ETTHArtikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Age- and gender-specific reference intervals are pivotal to ensure appropriate interpretation of plasma alkaline phosphatase activities in the lower range Hypophosphatasia (HPP) is an inborn error of metabolism caused by loss-of-function mutations of the ALPL gene that mainly express alkaline phosphatase (ALP) in bone and liver. The clinical expression of HPP is highly variable and is classified into six different forms mainly affecting bone and tooth mineralization. The prognosis for each of these HPP forms depends upon the severity of the skeletal disease which reflects the age at presentation. The biochemical hallmark of HPP is low plasma ALP activity (hypophosphatasemia); however, HPP is often misdiagnosed because of low awareness and sometimes absence of age- and gender-specific ALP reference intervals. Children and adolescents have higher ALP levels in comparison with adults. Reliable reference intervals are pivotal for any clinical laboratory test. Harmonized age- and gender-specific plasma ALP reference intervals ought to be used to ensure appropriate interpretation of plasma ALP activities in the lower range.

  • 32.
    Magnusson, Per
    et al.
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Nilsen, Per
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Schedvin, Göran
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Appropriate Use of Vitamin D Assessments in Primary Health Care: Impact of New Strategies for the Introduction and Follow-Up of Analyses in Östergötland2019Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116, nr 14, artikel-id FFPXArtikel i tidskrift (Refereegranskat)
  • 33.
    Magnusson, Per
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Nilsen, Per
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Schedvin, Göran
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    D-vitaminanalyser i primärvård måste användas ändamålsenligt [Appropriate use of vitamin D assessments in primary health care]: Ny strategi i Östergötland för införande och uppföljning av analyser gav bra resultat [Impact of new strategies for the introduction and follow-up of analyses in Östergötland]2019Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116, s. 1-4Artikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Hälso- och sjukvårdslagen föranstaltar om en kostnadseffektiv och jämlik diagnostik inom den svenska hälso- och sjukvården. Samtidigt ökar efterfrågan på laboratorietest mer än annan medicinsk aktivitet, och utvecklingen leder även till att utbudet av laboratorietest ökar [1]. Vårdens generella resursbrist har lett till ökad betoning på värdeskapande testanvändning globalt [2] med fokus på såväl underanvändning av test (försenar korrekt diagnos och adekvat behandling) som överanvändning (medför överdiagnostik och resursslöseri) [3].Som en följd av denna utveckling har laboratorieverksamheten inom Region Östergötland initierat strategier med syfte att åstadkomma en mer rationell användning av laboratoriemedicinska analyser. Detta har skett genom en aktivare uppföljning av beställningsmönster åtföljd av information och feedback i relation till observerade beställningsmönster. År 2016 initierades s k KRAMA-strategier (KRAMA = Kompetensgruppen för rationell användning av medicinsk diagnostik i alla delar av vårdkedjan) (Figur 1). En viktig ambition var att överge ett passivt testinförande till förmån för ett mer effektivt införande i kombination med aktiv uppföljning av beställningsmönster.

  • 34.
    Malmström, Annika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, LAH Linköping.
    Studies for Better Treatment of Patients with Glioma2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    In Sweden annually over 500 people will be diagnosed with the malignant brain tumor glioma. They are graded from I-IV. The majority are glioblastoma (grade IV) (GBM), these being the most aggressive type. Median survival for those treated with standard of care is expected to be around 15 months. This tumor will mainly affect those 60 years or older.

    The studies in this thesis focus on treatment of patients with malignant gliomas grade III and IV. The aim of the studies is to improve the care of glioma patients. Papers I and II explored different therapeutic options in randomized trials, to facilitate individualized treatment recommendations. Findings from studies I and II, together with additional trials, demonstrated the importance of analyzing the tumor marker O6-methylguanine DNA methyltransferase (MGMT) methylation status for survival of GBM patients treated with Temozolomide (TMZ). The third paper investigated how the analysis of this marker is implemented internationally.

    The first study (paper I, Nordic trial) investigated treatment options for patients 60 years or older with GBM. The trial compared standard radiotherapy (SRT) over 6 weeks versus hypofractionated radiotherapy (HRT) over 2 weeks versus single agent TMZ administered in up to six 4 weekly cycles. In all, 342 patients were included in the trial. This study demonstrated that those randomized to TMZ had superior survival as compared to SRT. In addition, quality of life (QoL) data also suggested a better QoL for TMZ treatment than for radiotherapy. The benefit of TMZ treatment seemed to be limited to those with the tumor molecular marker MGMT methylated (inactivated).

    The second trial (paper II, Neoadjuvant trial) studied whether integrating TMZ treatment with SRT for patients younger than 60 years with GBM (grade IV) and astrocytoma grade III would confer a survival benefit, if administered postoperatively, before the start of SRT (neoadjuvant). TMZ was provided for 2-3 four weekly cycles followed by SRT to patients randomized to neoadjuvant treatment and was compared to postoperative SRT alone. Although this trial could not illustrate any advantage of delaying the start of SRT while administering TMZ for the study cohort in general, for those included as astrocytoma grade III the median survival was found to be superior by 5 years when randomized to neoadjuvant TMZ. This trial also confirmed the importance of MGMT promoter methylation for the efficacy of TMZ.

    The third study (paper III) investigated international practices for analyzing tumor MGMT promoter methylation status. MGMT analysis can be conducted by various laboratory methods, which in some cases can provide opposing results regarding the MGMT methylation status of the patient´s tumor. This can lead to incorrect treatment recommendations. To establish which methods and cut-offs that are regularly used to determine tumor MGMT status in the clinic, an international survey was provided to those working in the field. We also inquired about opinions regarding an international consensus on how MGMT should be tested. The 152 respondents reported several methodologies and different cut-off levels also for the same method. A majority of respondents warrant international guidelines.

    In conclusion, the results of the 2 randomized trials contribute to individualized treatment recommendations for patients affected by GBM or astrocytoma grade III. The results of the survey regarding analyses of MGMT clarify the current problematic situation. The request of the respondents regarding international guidelines might contribute to their future development, so that personalized treatment recommendations can be improved.

    Delarbeten
    1. Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial
    Öppna denna publikation i ny flik eller fönster >>Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial
    Visa övriga...
    2012 (Engelska)Ingår i: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 13, nr 9, s. 916-926Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background Most patients with glioblastoma are older than 60 years, but treatment guidelines are based on trials in patients aged only up to 70 years. We did a randomised trial to assess the optimum palliative treatment in patients aged 60 years and older with glioblastoma. less thanbrgreater than less thanbrgreater thanMethods Patients with newly diagnosed glioblastoma were recruited from Austria, Denmark, France, Norway, Sweden, Switzerland, and Turkey. They were assigned by a computer-generated randomisation schedule, stratified by centre, to receive temozolomide (200 mg/m(2) on days 1-5 of every 28 days for up to six cycles), hypofractionated radiotherapy (34.0 Gy administered in 3.4 Gy fractions over 2 weeks), or standard radiotherapy (60.0 Gy administered in 2.0 Gy fractions over 6 weeks). Patients and study staff were aware of treatment assignment. The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered, number ISRCTN81470623. less thanbrgreater than less thanbrgreater thanFindings 342 patients were enrolled, of whom 291 were randomised across three treatment groups (temozolomide n=93, hypofractionated radiotherapy n=98, standard radiotherapy n=100) and 51 of whom were randomised across only two groups (temozolomide n=26, hypofractionated radiotherapy n=25). In the three-group randomisation, in comparison with standard radiotherapy, median overall survival was significantly longer with temozolomide (8.3 months [95% CI 7.1-9.5; n=93] vs 6.0 months [95% CI 5.1-6.8; n=100], hazard ratio [HR] 0.70; 95% CI 0.52-0.93, p=0.01), but not with hypofractionated radiotherapy (7.5 months [6.5-8.6; n=98], HR 0.85 [0.64-1.12], p=0.24). For all patients who received temozolomide or hypofractionated radiotherapy (n=242) overall survival was similar (8.4 months [7.3-9.4; n=119] vs 7.4 months [6.4-8.4; n=123]; HR 0.82, 95% CI 0.63-1.06; p=0.12). For age older than 70 years, survival was better with temozolomide and with hypofractionated radiotherapy than with standard radiotherapy (HR for temozolomide vs standard radiotherapy 0.35 [0.21-0.56], pandlt;0.0001; HR for hypofractionated vs standard radiotherapy 0.59 [95% CI 0.37-0.93], p=0.02). Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation (9.7 months [95% CI 8.0-11.4] vs 6.8 months [5.9-7.7]; HR 0.56 [95% CI 0.34-0.93], p=0.02), but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy (HR 0.97 [95% CI 0.69-1.38]; p=0.81). As expected, the most common grade 3-4 adverse events in the temozolomide group were neutropenia (n=12) and thrombocytopenia (n=18). Grade 3-5 infections in all randomisation groups were reported in 18 patients. Two patients had fatal infections (one in the temozolomide group and one in the standard radiotherapy group) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed. less thanbrgreater than less thanbrgreater thanInterpretation Standard radiotherapy was associated with poor outcomes, especially in patients older than 70 years. Both temozolomide and hypofractionated radiotherapy should be considered as standard treatment options in elderly patients with glioblastoma. MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide.

    Ort, förlag, år, upplaga, sidor
    Elsevier, 2012
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-84333 (URN)10.1016/S1470-2045(12)70265-6 (DOI)000308425600019 ()
    Anmärkning

    Funding Agencies|Merck||Lions Cancer Research Foundation||University of Umea||Swedish Cancer Society||Schering-Plough||University of Umea, Sweden||Cancer Fonden, Sweden||

    Tillgänglig från: 2012-10-05 Skapad: 2012-10-05 Senast uppdaterad: 2019-11-06
    2. Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial
    Öppna denna publikation i ny flik eller fönster >>Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial
    Visa övriga...
    2017 (Engelska)Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, nr 12, s. 1776-1785Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Introduction: A pilot study of temozolomide (TMZ) given before radiotherapy (RT) for anaplastic astrocytoma (AA) and glioblastoma (GBM) resulted in prolonged survival compared to historical controls receiving RT alone. We therefore investigated neoadjuvant TMZ (NeoTMZ) in a randomized trial. During enrollment, concomitant and adjuvant radio-chemotherapy with TMZ became standard treatment. The trial was amended to include concurrent TMZ.Patients and methods: Patients, after surgery for GBM or AA, age 60 years and performance status (PS) 0-2, were randomized to either 2-3 cycles of TMZ, 200mg/m(2) days 1-5 every 28 days, followed by RT 60Gy in 30 fractions or RT only. Patients without progressive disease after two TMZ cycles, received the third cycle. From March 2005, TMZ 75mg/m(2) was administered daily concomitant with RT. TMZ was recommended first-line treatment at progression. Primary endpoint was overall survival and secondary safety.Results: The study closed prematurely after enrolling 144 patients, 103 with GBM and 41 with AA. Median age was 53 years (range 24-60) and 89 (62%) were male. PS was 0-1 for 133 (92%) patients, 53 (37%) had complete surgical resection and 18 (12%) biopsy. Ninety-two (64%) received TMZ concomitant with RT. Seventy-two (50%) were randomized to neoadjuvant treatment. For the overall study population survival was 20.3 months for RT and 17.7 months for NeoTMZ (p=.76), this not reaching the primary objective. For the preplanned subgroup analysis, we found that NeoTMZ AA patients had a median survival of 95.1 months compared to 35.2 months for RT (p=.022). For patients with GBM, no difference in survival was observed (p=.10). MGMT and IDH status affected outcome.Conclusions: No advantage of NeoTMZ was noted for the overall study population or subgroup of GBM, while NeoTMZ resulted in 5 years longer median survival for patients diagnosed as AA.

    Ort, förlag, år, upplaga, sidor
    TAYLOR & FRANCIS LTD, 2017
    Nationell ämneskategori
    Kirurgi
    Identifikatorer
    urn:nbn:se:liu:diva-144005 (URN)10.1080/0284186X.2017.1332780 (DOI)000418118800016 ()28675067 (PubMedID)
    Anmärkning

    Funding Agencies|Merck; Linkoping University Hospital for Neuro-research; Lions Cancer Foundation; Cancer Foundation Norrland, Umea, Sweden; LIUCancer; South-East Sweden FORSS

    Tillgänglig från: 2018-01-02 Skapad: 2018-01-02 Senast uppdaterad: 2019-11-06
    3. Do we really know who has an MGMT methylated glioma?: Results of an international survey regarding use of MGMT analyses for glioma
    Öppna denna publikation i ny flik eller fönster >>Do we really know who has an MGMT methylated glioma?: Results of an international survey regarding use of MGMT analyses for glioma
    Visa övriga...
    2019 (Engelska)Ingår i: Neuro-Oncology Practice, ISSN 2054-2577, s. 1-9Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Glioma O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status informs clinical decision making. Worldwide different methods and cutoff levels are used, which can lead to discordant methylation results.We conducted an international survey to clarify which methods are regularly used and why. We also explored opinions regarding international consensus on methods and cutoff.The survey had 152 respondents from 25 countries. MGMT methylation status is determined for all glioblastomas in 37% of laboratories. The most common methods are methylation-specific polymerase chain reaction (msPCR) (37%) and pyrosequencing (34%). A method is selected for simplicity (56%), cost-effectiveness (50%), and reproducibility of results (52%). For sequencing, the number of CpG sites analyzed varies from 1–3 up to more than 16. For 50% of laboratories, the company producing the kit determines which CpG sites are examined, whereas 33% select the sites themselves. Selection of cutoff is equally distributed among a cutoff defined in the literature, by the local laboratory, or by the outside laboratory performing the analysis. This cutoff varies, reported from 1% to 30%, and in 1 laboratory tumor is determined as methylated in case of 1 methylated CpG site of 17 analyzed. Some report tumors as unmethylated or weakly vs highly methylated. An international consensus on MGMT methylation method and cutoff is warranted by 66% and 76% of respondents, respectively. The method preferred would be msPCR (45%) or pyrosequencing (42%), whereas 18% suggest next-generation sequencing.Although analysis of MGMT methylation status is routine, there is controversy regarding laboratory methods and cutoff level. Most respondents favor development of international consensus guidelines.

    Ort, förlag, år, upplaga, sidor
    Oxford: Oxford University Press, 2019
    Nationell ämneskategori
    Medicinsk biovetenskap Klinisk laboratoriemedicin
    Identifikatorer
    urn:nbn:se:liu:diva-160808 (URN)10.1093/nop/npz039 (DOI)
    Tillgänglig från: 2019-10-09 Skapad: 2019-10-09 Senast uppdaterad: 2019-11-06Bibliografiskt granskad
  • 35.
    Malmström, Annika
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Lysiak, Malgorzata
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Winther Kristensen, Bjarne
    Department of Pathology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Denmark.
    Hovey, Elizabeth
    Department of Medical Oncology, Nelune Comprehensive Cancer Centre, Prince of Wales Hospital , Randwick, Sydney, NSW, Australia University of New South Wales , Sydney, Australia.
    Henriksson, Roger
    Department of Radiation Sciences, University of Umeå , Sweden.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Do we really know who has an MGMT methylated glioma?: Results of an international survey regarding use of MGMT analyses for glioma2019Ingår i: Neuro-Oncology Practice, ISSN 2054-2577, s. 1-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Glioma O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status informs clinical decision making. Worldwide different methods and cutoff levels are used, which can lead to discordant methylation results.We conducted an international survey to clarify which methods are regularly used and why. We also explored opinions regarding international consensus on methods and cutoff.The survey had 152 respondents from 25 countries. MGMT methylation status is determined for all glioblastomas in 37% of laboratories. The most common methods are methylation-specific polymerase chain reaction (msPCR) (37%) and pyrosequencing (34%). A method is selected for simplicity (56%), cost-effectiveness (50%), and reproducibility of results (52%). For sequencing, the number of CpG sites analyzed varies from 1–3 up to more than 16. For 50% of laboratories, the company producing the kit determines which CpG sites are examined, whereas 33% select the sites themselves. Selection of cutoff is equally distributed among a cutoff defined in the literature, by the local laboratory, or by the outside laboratory performing the analysis. This cutoff varies, reported from 1% to 30%, and in 1 laboratory tumor is determined as methylated in case of 1 methylated CpG site of 17 analyzed. Some report tumors as unmethylated or weakly vs highly methylated. An international consensus on MGMT methylation method and cutoff is warranted by 66% and 76% of respondents, respectively. The method preferred would be msPCR (45%) or pyrosequencing (42%), whereas 18% suggest next-generation sequencing.Although analysis of MGMT methylation status is routine, there is controversy regarding laboratory methods and cutoff level. Most respondents favor development of international consensus guidelines.

    Publikationen är tillgänglig i fulltext från 2020-09-25 08:00
  • 36.
    Milovanovic, Micha
    et al.
    Östergötlands Läns Landsting, Närsjukvården i östra Östergötland, Medicinkliniken ViN.
    Nillsson, Ethel
    Östergötlands Läns Landsting, Närsjukvården i östra Östergötland, Medicinkliniken ViN.
    Järemo, Petter
    Östergötlands Läns Landsting, Närsjukvården i östra Östergötland, Medicinkliniken ViN.
    Relationships between platelets and inflammatory markers in rheumatoid arthritis2004Ingår i: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 343, nr 1-2, s. 237-240Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM OF THE STUDY: To investigate platelets and different inflammatory markers in conjunction with a substantial inflammatory reaction. We used individuals with active rheumatoid arthritis (RA) as an experimental cohort.

    METHODS: We selected 16 patients with active RA having at least one affected joint. On day 1, platelet and neutrophil counts together with C-reactive protein (CRP) were determined. We further analysed platelet volume (MPV) and plasma levels of thrombopoietin (TPO), P-selectin, myeloperoxidase and interleukin 6 (IL-6). After 2 years when all patients failed to show any swollen joints all analyses were repeated.

    RESULTS AND CONCLUSIONS: As expected platelet count, CRP and IL-6 were elevated in active RA. The measures correlated with each other thus reflecting the same characteristic of the inflammatory response. The neutrophil count, MPV and myeloperoxidase also mirror disease activity. They failed to correlate with other activity markers thus providing unique information. MPV and myeloperoxidase on day 1 correlated with recovery values. Therefore, they could be suitable to use when following the inflammatory reaction over a long period of time.

  • 37.
    Monstein, Hans-Jurg
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Quenadu, Michael
    Laboratory of Food hygiene, Department of Food Thecnology, University of Lund.
    Samuelsson, Annika
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Ahrne, Siv
    Laboratory of Food hygiene, Department of Food Thecnology, University of Lund.
    Isaksson, Barbro
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Jonasson, Jon
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Klinisk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Division of the genus Enterococcus into species groups using PCR-based molecular typing methods1998Ingår i: Microbiology, ISSN 1350-0872, E-ISSN 1465-2080, Vol. 144, nr 5, s. 1171-1179Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Broad-range 16S rDNA PCR (BR-PCR) applied to DNA from 32 clinical enterococcal isolates and 12 other enterococci from a clinical reference collection followed by species-specific hybridization analysis identified 25 strains of Enterococcus faecalis and 19 Enterococcus species. Randomly amplified polymorphic DNA (RAPD) analysis using UPGMA clustering on the same material revealed four different clusters at a similarity level of 49%. Based on partial 16S rDNA sequence analysis of variable regions V4 and V9, it was possible to divide the 19 type strains specifying the genus Enterococcus into 12 different 16S rDNA species groups. The type strain distribution then served as a template for the analysis of the other 44 strains which were assigned to four different species groups (a-d) based on their 16S rDNA motifs. There was good agreement with the RAPD clusters. Species group a was an individual species line containing 25 strains that were identified as E. faecalis. Group b also represented an individual species line of 12 strains identified as E. faecium. The remaining seven strains that formed species groups c and d could not be fully identified to species by this analysis. It was concluded that BR-PCR of 16S rDNA followed by partial sequence analysis of the PCR products is a reliable technique for the identification and classification of enterococci. Further division of unresolved species groups should be achievable if regions other than V4 and V9 of 16S rDNA are also analysed

  • 38.
    Nastic, Denis
    et al.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Shanwell, Emma
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Wallin, Keng-Ling
    Equalis, Sweden.
    Valla, Marit
    Norwegian University of Science and Technology, Norway.
    Masback, Anna
    Lund University Hospital, Sweden.
    Mateoiu, Claudia
    Sahlgrens University Hospital, Sweden.
    Lidang, Marianne
    Herlev University Hospital, Denmark.
    Liakka, Annikki
    Oulu University Hospital, Finland.
    Lappi-Blanco, Elisa
    Oulu University Hospital, Finland.
    Grove, Anni
    Aalborg University Hospital, Denmark.
    Davidson, Ben
    University of Oslo, Norway.
    Carpen, Olli
    University of Turku, Finland; Turku University Hospital, Finland.
    Bertelsen, Bjorn I.
    Haukeland Hospital, Norway.
    Bak, Julia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Abusland, Anne B.
    Trondheim Regional and University Hospital, Norway.
    Selling, Jonas
    Statsoft AB, Sweden.
    Carlson, Joseph W.
    Karolinska University Hospital, Sweden; Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    A Selective Biomarker Panel Increases the Reproducibility and the Accuracy in Endometrial Biopsy Diagnosis2017Ingår i: International Journal of Gynecological Pathology, ISSN 0277-1691, E-ISSN 1538-7151, Vol. 36, nr 4, s. 339-347Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Grading and histologic typing of endometrial cancer in biopsy material has a direct impact on the decision to perform lymphadenectomy and/or omentectomy in many cancer centers. Endometrial biopsies are among the most common general surgical pathology specimens. Multiple studies have shown that biopsy diagnosis suffers from a lack of reproducibility. Although many biomarkers have been proposed, none have been demonstrated to improve the diagnosis in the biopsy setting. In this study, 70 biopsies with endometrial carcinoma were supplemented with a biomarker panel consisting of ER, PR, P53, and DNA ploidy. A representative Hamp;E slide was scanned digitally and made available to 12 gynecologic pathologists in 4 Nordic countries: Finland, Denmark, Sweden, and Norway. Reviewers diagnosed the cases both before and after being provided with the biomarker results. The interobserver percent agreement and Cohen kappa improved from 75.8% (kappa = 0.52, moderate) to 84% (kappa = 0.68, substantial) with inclusion of the biomarker panel. Agreement with the subsequent hysterectomy diagnosis also improved from 83.6% (kappa = 0.67) to 88.7% (kappa = 0.77). There was no statistical improvement between a reflex (84% agreement) and a reflective testing algorithm (82.9% agreement), suggesting that the selective use of biomarkers is appropriate. Difficult cases were almost exclusively high-grade tumors. Finally, a statistical model indicated that only P53 and DNA ploidy, in conjunction with an Hamp;E review, had an impact on the decision to upgrade or downgrade cases.

  • 39.
    Olsson, Hans
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Hultman, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Monsef, Nastaran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Johanson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Urologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Immunohistochemical Evaluation of Cell Cycle Regulators: Impact on Predicting Prognosis in Stage T1 Urinary Bladder Cancer2012Ingår i: ISRN Urology, ISSN 2090-5807, E-ISSN 2090-5815, Vol. 2012, artikel-id 379081Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background and Objective. The cell cycle is regulated by proteins at different checkpoints, and dysregulation of this cycle plays a role in carcinogenesis. Matrix metalloproteinases (MMPs) are enzymes that degrade collagen and promote tumour infiltration. The aim of this study was to evaluate the expression of various cell cycle regulators and MMPs, and to correlate such expression with progression and recurrence in patients with stage T1 urothelial carcinoma of the bladder (UCB).

    Patients and Methods. This population-based cohort study comprised 201 well-characterized patients with primary stage T1 urothelial carcinoma of the bladder. Immunohistochemistry was performed on formalin-fixed material to quantify expression of cell cycle regulators and two MMPs.

    Results. Normal expression of p53 and abnormal expression of MMP9 were associated with greater risk of tumour recurrence. Also, normal p16 expression was related to a lower risk of tumour progression. MMP2, p21, cyclin D1, and pRb showed no significant results that could estimate progression or recurrence.

    Conclusions. Normal p16 expression is associated with a lower risk of tumour progression, but immunohistochemistry on cell cycle regulators and MMPs has little value in predicting the prognosis in stage T1 UCB.

  • 40.
    Parenmark, Anna
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Landberg, Eva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    To mix or not to mix venous blood samples collected in vacuum tubes?2011Ingår i: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 49, nr 12, s. 2061-2063Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There are recommendations to mix venous blood samples by inverting the tubes immediately after venipuncture. Though mixing allows efficient anticoagulation in plasma tubes and fast initiation of coagulation in serum tubes, the effect on laboratory analyses and risk of haemolysis has not been thoroughly evaluated. less thanbrgreater than less thanbrgreater thanMethods: Venous blood samples were collected by venipuncture in vacuum tubes from 50 patients (10 or 20 patients in each group). Four types of tubes and 18 parameters used in routine clinical chemistry were evaluated. For each patient and tube, three types of mixing strategies were used: instant mixing, no mixing and 5 min of rest followed by mixing. less thanbrgreater than less thanbrgreater thanResults: Most analyses did not differ significantly in samples admitted to different mixing strategies. Plasma lactate dehydrogenase and haemolysis index showed a small but significant increase in samples omitted to instant mixing compared to samples without mixing. However, in one out of twenty non-mixed samples, activated partial thromboplastin time was seriously affected. less thanbrgreater than less thanbrgreater thanConclusions: These results indicate that mixing blood samples after venipuncture is not mandatory for all types of tubes. Instant mixing may introduce interference for those analyses susceptible to haemolysis. However, tubes with liquid-based citrate buffer for coagulation testing should be mixed to avoid clotting.

  • 41.
    Sandberg, Alexander
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Purification and Fibrillation of Recombinant Human Amyloid-ß, Prion Protein, and Tau Under Native Conditions2018Ingår i: Amyloid Proteins: Methods and Protocols / [ed] Einar M. Sigurdsson, Miguel Calero and María Gasset, Humana Press, 2018, Vol. 1779, s. 147-166Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    Protein misfolding, aggregation, and amyloid formation is involved in a large number of diseases. Recombinantly expressed proteins to study the amyloid fibril formation process are important for mechanistic studies. We here report protocols for production, purification, and fibrillation of three different proteins commonly found in cerebral amyloid; Aß and Tau found in Alzheimers disease, Chronic traumatic brain injury, Corticobasal degeneration, and Progressive Supranuclear Palsy and human prion protein found in Creutzfeldt-Jakobs disease. The three protocols have in common that the protein is in a pH-neutral phosphate saline buffer during fibrillation to mimic their endogenous near physiological environment.

  • 42.
    Sandholm, Kerstin
    et al.
    Linnaeus University, Kalmar, Sweden.
    Carlsson, Hanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Department of Clinical Chemistry and Transfusion Medicine, Kalmar, Region Kalmar County.
    Persson, Barbro
    Uppsala University, Uppsala, Sweden.
    Skattum, Lillemor
    Lund University, Lund, Sweden; Clinical Immunology and Transfusion Medicine, Lund, Sweden..
    Tjernberg, Ivar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi, infektion och inflammation. Linköpings universitet, Medicinska fakulteten.
    Nilsson, Bo
    Uppsala University, Uppsala, Sweden.
    Ekdahl, Kristina N
    Linnaeus University, Kalmar, Sweden; Uppsala University, Uppsala, Sweden.
    Discrepancies in plasma levels of complement components measured by a newly introduced commercially available magnetic bead technique compared to presently available clinical reference intervals2019Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, artikel-id e12831Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Complement system aberrations are implicated in numerous pathological conditions. Techniques used in complement diagnostic include monitoring of individual proteins, activation products or function using different types of immunoassays. Most recent techniques include multiplex assays which enable simultaneous detection of multiple complement components or activation products in the same sample thereby saving both sample volume and time.

    MATERIALS AND METHODS: We have tested the performance of the commercially available Human Complement Magnetic Bead multiplex assay MILLIPLEX MAP H (EMD Millipore Corporation, Billerica, MA, USA) for simultaneous determination of C1q, C4, C3, factor B, properdin and factor H as well as MBL, C2, factor D, factor I, C5 and C9 using plasma from 68 healthy blood donors.

    RESULTS: The main observation was very low levels of C3 determined by the MILLIPLEX assay: median value 16.4 mg/L (range 7.7-57.4) compared to the present reference value of 670-1290 mg/L used in the clinic (i.e., 60-fold lower). Discrepancies (although not as pronounced as for C3) were also found for C1q, factor B, factor H, C2 and C9.

    CONCLUSION: The MILLIPEX assay is highly inaccurate regarding C3 and less reliable for several other analytes, and implies that the company should reconstruct their assay for C3 since the results are not on par with the standard of other techniques used today.

  • 43.
    Shamoun, Levar
    et al.
    Jonköping County, Sweden.
    Kolodziej, Blanka
    Jonköping County, Sweden.
    Andersson, Roland
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Jönköping County, Sweden.
    Dimberg, Jan
    Jonköping University, Sweden.
    Protein Expression and Genetic Variation of IL32 and Association with Colorectal Cancer in Swedish Patients2018Ingår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 38, nr 1, s. 321-328Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Interleukin 32 (IL32) is an intracellular pluripotent cytokine produced by epithelial cells, monocytes, T-lymphocytes and natural killer cells and seems to be involved in the pathogenesis of cancer and inflammatory diseases. Our purpose was to assess the role of protein expression and genetic polymorphisms of IL32 in colorectal cancer (CRC) susceptibility. Materials and Methods: To gain insight into clinical significance of IL32 in Swedish patients with CRC, using enzyme-linked immunosorbent assay, we determined whether IL32 protein level is altered in CRC tissue (n=75) compared with paired normal tissue and in plasma from patients with CRC (n=94) compared with controls (n=81). The expression of IL32 protein was confirmed by immunohistochemistry (n=73). We used Luminex technology to investigate protein levels of the cytokines IL6, tumor necrosis factor-a (TNFa) and vascular endothelial growth factor (VEGF) to relate these to IL32 levels in CRC tissue. Three single nucleotide polymorphisms (SNPs) (rs28372698, rs12934561, rs4786370) of the IL32 gene have been proposed as modifiers for different diseases. The present study evaluated the susceptibility of patients possessing these SNPs to CRC. Using TaqMan SNP genotyping assays, these SNPs were screened in Swedish patients with CRC (n=465) and healthy controls (n=331). Results: We found no significant differences in the genotypic frequencies between the patients and healthy controls and no relation to survival for any of the SNPs. However, the SNP rs12934561 was statisticalLY significant associated with older patients. IL32 protein was up-regulated in CRC tissue and related to IL6, TNF alpha, and VEGF, and seems to be modulated by SNP rs28372698. The IL32 protein level in CRC tissue also reflects both disseminated disease and location. Conclusion. Our results suggest that altered IL32 protein concentrations in CRC tissue and genotypic variants of IL32 are related to disseminated CRC.

  • 44.
    Simonsson, Per
    et al.
    Siemens healthineers, Solna, Sweden.
    Tjernberg, Ivar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi, infektion och inflammation. Linköpings universitet, Medicinska fakulteten. Landstinget i Kalmar län, Kalmar, Sweden.
    Egenordinerad provtagning kan ge laboratoriemedicinen ny roll [Patient-initiated diagnostics - a challenge for laboratory medicine]2019Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116, artikel-id FIFWArtikel i tidskrift (Övrigt vetenskapligt)
    Abstract [sv]

    Citizens can now order their own laboratory investigations. Self-testing is in line with increasing patient empowerment and in conflict with existing routines in medicine where all tests are ordered by the physician. Several challenges have to be faced by laboratory medicine to secure the quality and increase the medical benefits of patient-initiated diagnostics.

  • 45.
    Stoltzfus, Patricia
    et al.
    Division of Cellular and Molecular Tumor Pathology, Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Hospital, Stockholm, Sweden.
    Salo, Sirpa
    Department of Biochemistry, University of Oulu, Finland.
    Eriksson, Elina
    Division of Cellular and Molecular Tumor Pathology, Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Hospital, Stockholm, Sweden.
    Aspenblad, Ulla
    Division of Cellular and Molecular Tumor Pathology, Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Hospital, Stockholm, Sweden.
    Tryggvason, Karl
    Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
    Auer, Gert
    Division of Cellular and Molecular Tumor Pathology, Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Hospital, Stockholm, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Gynecological Oncology, Department of Oncology and Pathology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
    Laminin-5 gamma2 chain expression facilitates detection of invasive squamous cell carcinoma of the uterine cervix.2004Ingår i: International Journal of Gynecological Pathology, ISSN 0277-1691, E-ISSN 1538-7151, Vol. 23, nr 3, s. 215-222Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Because it has been suggested that laminin-5 can be used as a sensitive marker for epithelial cell invasion, specimens from patients with invasive squamous cell carcinoma of the uterine cervix with a previous history of preinvasive lesions were evaluated by a newly developed monoclonal antibody directed against the gamma2 chain of laminin-5. Thirty-two archival paraffin specimens consisting of the matched preinvasive and invasive lesions from 15 women were evaluated to determine whether gamma2 chain laminin-5 staining was present in lesions that progressed to invasive cancer. With the exception of one tumor (a small cell nonkeratinizing squamous carcinoma), all squamous cell carcinomas exhibited positive staining. Five of 17 preinvasive lesions also were immunoreactive for the laminin-5 protein. A blinded histologic reevaluation revealed invasion or lesions suspicious for invasion in four of five preinvasive lesions. Our findings suggest that laminin-5 determined by a monoclonal antibody facilitates the identification of invasive lesions that are difficult or impossible to identify on routinely stained histologic sections.

  • 46.
    Sörbo, Ann
    et al.
    Department of Neuro- and Rehabilitation, Southern Älvsborg Hospital, Borås, Sweden.
    Eiving, I.
    Department of Anesthesiology and Intensive Care, Sahlgrenska University Hospital, Göteborg, Sweden.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Rydenhag, B.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Göteborg, Sweden.
    Hair Cortisol as a Biomarker of Stress before and after Subarachnoid Hemorrhage: A Case Report2017Ingår i: Remedy Open Access, E-ISSN 2573-6078, Vol. 2, artikel-id 1062Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim was to study stress in the acute and post-acute phase in patients with severe traumaticbrain injury (TBI) or non-traumatic subarachnoid hemorrhage (SAH) who were treated at theneurointensive care unit (NICU). Hair cortisol is a biomarker of stress via alterations in hypothalamuspituitary-adrenal axis activity, where cortisol from plasma is continuously incorporated intogrowing hairs at their roots. As hair grows at an average of 1 cm/month, concentrations of haircortisol can also be used to measure stress levels retrospectively.

    Hair samples were collected at an interval of one month until three months, with the first cut atadmission to the NICU. The patients (or their relatives, if the patient was unable to communicate)were interviewed about psychological or physical stressors during the previous months.

    We present a 28-year-old woman suffering from a subarachnoid hemorrhage (SAH), studied withrepeated haircuts. She experienced the sudden onset of a severe headache. The general practitionersdiagnosed it as migraine or wry neck. Three weeks later, she experienced another attack ofsevere headache. A CT scan showed an SAH. Six months after the SAH, the patient developedhydrocephalus and was successfully treated with a VP shunt. In this case, hair cortisol was elevatedduring the pre-hospital month (probably because of pain and stress due to a sentinel or “warning”leak), during the intensive care period and until two months after the SAH. It then normalized, butit was elevated again at the time at which the patient developed hydrocephalus. At the nine-monthhaircut, her hair cortisol had again normalized.

    This case indicates that hair cortisol measurement is a promising method for studying stress,retrospectively and during recovery, in patients suffering from SAH.

  • 47.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Labbdiagnostik av sällsynta sjukdomar kan bli bättre: Både metodernas tillförlitlighet och personalens medvetenhet spelar roll - ornitos är ett bra exempel2018Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115, artikel-id FDI3Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Psittacosis (parrot fever) is underdiagnosed in Sweden, possibly due to lack of awareness, and the fact that only five out of 24 clinical microbiology laboratories routinely perform the PCR test for Chlamydia psittaci. The test has shown 100% sensitivity and 100% sensitivity for the pathogen in samples from the lower part of the respiratory tract which caters for a high predictive value in patients with symptoms and signs of community-acquired atypical pneumonias, provided optimal patient selection. Knowledge and awareness of treatable rare diseases amongst healthcare personnel combined with conveniently available cost-effective diagnostic techniques is essential for improvements in the handling of rare diseases.

  • 48.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Validation and verification in clinical chemistry2017Ingår i: Klinisk biokemi i Norden, ISSN 1101-2013, Vol. 1, nr 29, s. 8-16Artikel, forskningsöversikt (Övrigt vetenskapligt)
    Abstract [en]

    Measurement systems used inclinical chemistry are usuallymanufactured by internationalcompanies working according toin vitro directive (IVD) – regulations.This means that medicallaboratories do not need to validatecommercially available measurement systems,but are obliged to verify that their properties foundduring the producers validation can be reproducedin the users laboratories. Developments in healthcareand accreditation standards including ISO 15189focus increasingly on customer needs which maycall for the validation of entire conglomerates oflaboratories and measurement systems catering forthe needs for the same patient population. Such validationpractices are, however, still in their infancy.The purpose of the present paper is to offer practicaldetails on the common practice of verificationof single measurement systems and add perspectiveson the validation of conglomerates of laboratoriesand measurement systems. Method validation acrossconglomerates of laboratories using verified commerciallyavailable measurement systems can only beperformed by the laboratories – users themselves intheir own circumstances. The use of patient samplesin split- sample techniques is especially valuable inthis contexts in order to avoid compatibility issues.

  • 49.
    Theodorsson, Elvar
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Berggren Söderlund, Maria
    Region Kronoberg, Klinisk kemi och transfusionsmedicin.
    Laurells klinisk kemi i praktisk medicin2018 (uppl. 10)Bok (Övrigt vetenskapligt)
    Abstract [sv]

    Denna tionde upplaga av Laurells Klinisk kemi i praktisk medicin utgör en grundlig bearbetning av det populära verket. Samtliga kapitel har reviderats och kapitlen om tolkning av analysresultat, vatten, elektrolyter, blodgaser, mag–tarmkanalen och immunologi har skrivits om från grunden; allt i samarbete mellan verksamma inom klinisk farmakologi, klinisk immunologi och klinisk kemi.?

    Kunskapsfragment inom medicin, inklusive klinisk kemi, är lättillgängliga på nätet men ger sällan den helhetsbild som behövs för en djupare förståelse och därmed optimal användning av laboratorie­analyser. Denna bok ger en sådan helhetsbild och kan användas såväl för att slå upp fakta om specifika analyser som för att förstå de sjukdomsmekanismer som är av betydelse för beställning och tolkning av laboratorieresultat.?

    Texten är organiserad utifrån kliniska problemområden och i balansgången mellan inslagen av laboratorium och medicin har tonvikten lagts på det medicinskt-diagnostiska snarare än på det laboratorietekniska. Fokus ligger på förståelsen av preanalytiska och analytiska faktorer vid tolkningen av laboratorieresultat samt av förståelsen av prevalens, sensitivitet, specificitet och liknande begrepp i det diagnostiska arbetet.?

    Föreliggande bok förväntas även fortsatt komma till god användning på avdelningar, mottagningar och vårdcentraler – överallt där man behöver ta laboratorieprover och tolka provsvar – men också bland studenter i medicin, biomedicin, biomedicinsk laboratorievetenskap och besläktade kunskapsområden.

  • 50.
    Theodorsson, Elvar
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Löwbeer, Christian
    Aleris Medilab och Institutionen för laboratoriemedicin, Avdelningen för klinisk kemi, Karolinska institutet, Stockholm.
    Ridefelt, Peter
    Institutionen för medicinska vetenskaper, Klinisk kemi, Uppsala universitet.
    Carlson, Marie
    Institutionen för sociologi och arbetsvetenskap, Göteborgs universitet.
    Dahle, Charlotte
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk immunologi och transfusionsmedicin.
    Simonsson, Per
    Institutionen för translationell medicin, Medicinska fakulteten, Lunds universitet.
    Digestionsorganens sjukdomar2018Ingår i: Laurells klinisk kemi i praktisk medicin, Lund: Studentlitteratur AB, 2018, 10, s. 465-516Kapitel i bok, del av antologi (Övrigt vetenskapligt)
12 1 - 50 av 58
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf