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  • 101.
    Berglund, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Kinch, Amelie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Edman, Elin
    Halmstad Hospital.
    Backlin, Carin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Molin, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Pauksens, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Baecklund, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Expression of Intratumoral Forkhead Box Protein 3 in Posttransplant Lymphoproliferative Disorders: Clinical Features and Survival Outcomes2015In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 99, no 5, p. 1036-1042Article in journal (Refereed)
    Abstract [en]

    Background. The infiltration of regulatory T cells (Tregs) in lymphomas is associated with better prognosis for some types of lymphomas, but knowledge of their role in posttransplant lymphoproliferative disorders (PTLDs) is limited. We therefore investigated the association between the expression of the Treg marker forkhead box protein 3 (FoxP3) in biopsies of PTLDs and survival, PTLD subtype, and clinical characteristics.

    Methods. Seventy-four cases of PTLD after solid organ transplantation with sufficient material for further analysis were included from a population-based study of PTLDs in Sweden. The PTLD biopsies were reevaluated and stained with the 236A/E7 antibody to detect FoxP3 in lymphoma tissue. Detailed clinical data were collected retrospectively from medical records.

    Results. Based on a cutoff level of 29 FoxP3+ cells per mm2, most (80%) of the PTLDs were FoxP3-. Forty-seven of 74 PTLDs displayed no FoxP3+ cells at all. The frequency of FoxP3+ cells did not influence median overall survival. The FoxP3- PTLDs were more frequently of T-cell phenotype (P=0.04), located at the graft (P=0.03), occurred earlier after transplantation (P=0.04), were more likely to develop in lung recipients (P=0.04), and in patients that had received anti T-cell globulin as induction therapy (P=0.02). The FoxP3+ PTLDs were associated with hepatitis C seropositivity (P=0.03). In multivariate analysis, B-cell PTLD and hepatitis C infection were independent predictors of FoxP3 positivity.

    Conclusion. Our findings suggest that intratumoral FoxP3+ Tregs do not influence survival in patients with PTLD. FoxP3+ Tregs are rare in PTLD, possibly because of heavy immunosuppression.

  • 102.
    Berglund, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Separation of Water and Fat Signal in Magnetic Resonance Imaging: Advances in Methods Based on Chemical Shift2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Magnetic resonance imaging (MRI) is one of the most important diagnostic tools of modern healthcare. The signal in medical MRI predominantly originates from water and fat molecules. Separation of the two components into water-only and fat-only images can improve diagnosis, and is the premier non-invasive method for measuring the amount and distribution of fatty tissue.

    Fat-water imaging (FWI) enables fast fat/water separation by model-based estimation from chemical shift encoded data, such as multi-echo acquisitions. Qualitative FWI is sufficient for visual separation of the components, while quantitative FWI also offers reliable estimates of the fat percentage in each pixel. The major problems of current FWI methods are long acquisition times, long reconstruction times, and reconstruction errors that degrade image quality.

    In this thesis, existing FWI methods were reviewed, and novel fully automatic methods were developed and evaluated, with a focus on fast 3D image reconstruction. All MRI data was acquired on standard clinical scanners.

    A triple-echo qualitative FWI method was developed for the specific application of 3D whole-body imaging. The method was compared with two reference methods, and demonstrated superior image quality when evaluated in 39 volunteers.

    The problem of qualitative FWI by dual-echo data with unconstrained echo times was solved, allowing faster and more flexible image acquisition than conventional FWI. Feasibility of the method was demonstrated in three volunteers and the noise performance was evaluated.

    Further, a quantitative multi-echo FWI method was developed. The signal separation was based on discrete whole-image optimization. Fast 3D image reconstruction with few reconstruction errors was demonstrated by abdominal imaging of ten volunteers.

    Lastly, a method was proposed for quantitative mapping of average fatty acid chain length and degree of saturation. The method was validated by imaging different oils, using gas-liquid chromatography (GLC) as the reference. The degree of saturation agreed well with GLC, and feasibility of the method was demonstrated in the thigh of a volunteer.

    The developed methods have applications in clinical settings, and are already being used in several research projects, including studies of obesity, dietary intervention, and the metabolic syndrome.

    List of papers
    1. Three-point Dixon method enables whole-body water and fat imaging of obese subjects
    Open this publication in new window or tab >>Three-point Dixon method enables whole-body water and fat imaging of obese subjects
    2010 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 63, no 6, p. 1659-1668Article in journal (Refereed) Published
    Abstract [en]

    Dixon imaging techniques derive chemical shift-separated water and fat images, enabling the quantification of fat content and forming an alternative to fat suppression. Whole-body Dixon imaging is of interest in studies of obesity and the metabolic syndrome, and possibly in oncology. A three-point Dixon method is proposed where two solutions are found analytically in each voxel. The true solution is identified by a multiseed three-dimensional region-growing scheme with a dynamic path, allowing confident regions to be solved before unconfident regions, such as background noise. 2 pi-Phase unwrapping is not required. Whole-body datasets (256 x 184 x 252 voxels) were collected from 39 subjects (body mass index 19.8-45.4 kg/m(2)), in a mean scan time of 5 min 15 sec. Water and fat images were reconstructed offline, using the proposed method and two reference methods. The resulting images were subjectively graded on a four-grade scale by two radiologists, blinded to the method used. The proposed method was found superior to the reference methods. It exclusively received the two highest grades, implying that only mild reconstruction failures were found. The computation time for a whole-body dataset was 1 min 51.5 sec +/- 3.0 sec. It was concluded that whole-body water and fat imaging is feasible even for obese subjects, using the proposed method.

    Keywords
    three-point Dixon, whole-body MRI, water and fat separation, chemical shift imaging, fat suppression
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-129498 (URN)10.1002/mrm.22385 (DOI)000278164400026 ()20512869 (PubMedID)
    Available from: 2010-08-17 Created: 2010-08-17 Last updated: 2017-12-12Bibliographically approved
    2. Two-point dixon method with flexible echo times
    Open this publication in new window or tab >>Two-point dixon method with flexible echo times
    2011 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 65, no 4, p. 994-1004Article in journal (Refereed) Published
    Abstract [en]

    The two-point Dixon method is a proton chemical shift imaging technique that produces separated water-only and fat-only images from a dual-echo acquisition. It is shown how this can be achieved without the usual constraints on the echo times. A signal model considering spectral broadening of the fat peak is proposed for improved water/fat separation. Phase errors, mostly due to static field inhomogeneity, must be removed prior to least-squares estimation of water and fat. To resolve ambiguity of the phase errors, a corresponding global optimization problem is formulated and solved using a message-passing algorithm. It is shown that the noise in the water and fat estimates matches the Cramér-Rao bounds, and feasibility is demonstrated for in vivo abdominal breath-hold imaging. The water-only images were found to offer superior fat suppression compared with conventional spectrally fat suppressed images.

    Keywords
    chemical shift imaging, fat suppression, two-point Dixon, water and fat separation
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-150936 (URN)10.1002/mrm.22679 (DOI)000288612000011 ()21413063 (PubMedID)
    Available from: 2011-04-08 Created: 2011-04-08 Last updated: 2017-12-11Bibliographically approved
    3. Three-dimensional water/fat separation and T2* estimation based on whole-image optimization: application in breathhold liver imaging at 1.5 T
    Open this publication in new window or tab >>Three-dimensional water/fat separation and T2* estimation based on whole-image optimization: application in breathhold liver imaging at 1.5 T
    2012 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 67, no 6, p. 1684-1693Article in journal (Refereed) Published
    Abstract [en]

    The chemical shift of water and fat resonances in proton MRI allows separation of water and fat signal from chemical shift encoded data. This work describes an automatic method that produces separate water and fat images as well as quantitative maps of fat signal fraction and T2* from complex multi-echo gradient recalled datasets. Accurate water and fat separation is challenging due to signal ambiguity at the voxel level. Whole-image optimization can resolve this ambiguity, but might be computationally demanding, especially for three-dimensional (3D) data. In this work, periodicity of the model fit residual as a function of the off-resonance was utilized to modify a previously proposed formulation of the problem. This gives a smaller solution space and allows rapid optimization. Feasibility and accurate separation of water and fat signal was demonstrated in breathhold 3D liver imaging of ten volunteer subjects, with both acquisition and reconstruction times below 20 seconds.

    Keywords
    water and fat separation, chemical shift imaging, quantitative MRI, liver fat, T2* mapping, QPBO
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-158097 (URN)10.1002/mrm.23185 (DOI)000304086000020 ()22189760 (PubMedID)
    Available from: 2011-08-31 Created: 2011-08-31 Last updated: 2017-12-08Bibliographically approved
    4. Model-based mapping of fat unsaturation and chain length by chemical shift imaging: phantom validation and in vivo feasibility
    Open this publication in new window or tab >>Model-based mapping of fat unsaturation and chain length by chemical shift imaging: phantom validation and in vivo feasibility
    2012 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 68, no 6, p. 1815-1827Article in journal (Refereed) Published
    Abstract [en]

    Knowledge about the triglyceride (fat) 1H spectrum enables quantitative determination of several triglyceride characteristics. This work describes a model-based chemical shift imaging method that separates water and fat signal and provides maps of three triglyceride quantities: fatty acid carbon chain length (CL), number of double bond pairs (ndb), and number of methylene-interrupted double bonds (nmidb). The method was validated by imaging a phantom containing ten different oils using 1.5 T and 3.0 T clinical scanners, with gas-liquid chromatography (GLC) as reference. Repeated acquisitions demonstrated high reproducibility of the method. Statistical tests of correlation and linear regression were performed to examine the accuracy of the method. Significant correlation was found at both field strengths for all three quantities, and high correlation (r2 > 0.96) was found for measuring ndb and nmidb. Feasibility of the method for in vivo imaging of the thigh was demonstrated at both field strengths. The estimates of ndb and nmidb in subcutaneous adipose tisse were in agreement with literature values, while CL appears overestimated. The method has potential use in large-scale cross-sectional and longitudinal studies of triglyceride composition, and its relation to diet and various diseases.

    Keywords
    water/fat separation, chemical shift imaging, quantitative MRI, fat unsaturation, triglyceride mapping, fatty acid composition
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:uu:diva-158098 (URN)10.1002/mrm.24196 (DOI)000311398600015 ()22334300 (PubMedID)
    Available from: 2011-08-31 Created: 2011-08-31 Last updated: 2017-12-08Bibliographically approved
  • 103.
    Berglund, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Two-point dixon method with flexible echo times2011In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 65, no 4, p. 994-1004Article in journal (Refereed)
    Abstract [en]

    The two-point Dixon method is a proton chemical shift imaging technique that produces separated water-only and fat-only images from a dual-echo acquisition. It is shown how this can be achieved without the usual constraints on the echo times. A signal model considering spectral broadening of the fat peak is proposed for improved water/fat separation. Phase errors, mostly due to static field inhomogeneity, must be removed prior to least-squares estimation of water and fat. To resolve ambiguity of the phase errors, a corresponding global optimization problem is formulated and solved using a message-passing algorithm. It is shown that the noise in the water and fat estimates matches the Cramér-Rao bounds, and feasibility is demonstrated for in vivo abdominal breath-hold imaging. The water-only images were found to offer superior fat suppression compared with conventional spectrally fat suppressed images.

  • 104.
    Berglund, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Model-based mapping of fat unsaturation and chain length by chemical shift imaging: phantom validation and in vivo feasibility2012In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 68, no 6, p. 1815-1827Article in journal (Refereed)
    Abstract [en]

    Knowledge about the triglyceride (fat) 1H spectrum enables quantitative determination of several triglyceride characteristics. This work describes a model-based chemical shift imaging method that separates water and fat signal and provides maps of three triglyceride quantities: fatty acid carbon chain length (CL), number of double bond pairs (ndb), and number of methylene-interrupted double bonds (nmidb). The method was validated by imaging a phantom containing ten different oils using 1.5 T and 3.0 T clinical scanners, with gas-liquid chromatography (GLC) as reference. Repeated acquisitions demonstrated high reproducibility of the method. Statistical tests of correlation and linear regression were performed to examine the accuracy of the method. Significant correlation was found at both field strengths for all three quantities, and high correlation (r2 > 0.96) was found for measuring ndb and nmidb. Feasibility of the method for in vivo imaging of the thigh was demonstrated at both field strengths. The estimates of ndb and nmidb in subcutaneous adipose tisse were in agreement with literature values, while CL appears overestimated. The method has potential use in large-scale cross-sectional and longitudinal studies of triglyceride composition, and its relation to diet and various diseases.

  • 105.
    Berglund, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Three-dimensional water/fat separation and T2* estimation based on whole-image optimization: application in breathhold liver imaging at 1.5 T2012In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 67, no 6, p. 1684-1693Article in journal (Refereed)
    Abstract [en]

    The chemical shift of water and fat resonances in proton MRI allows separation of water and fat signal from chemical shift encoded data. This work describes an automatic method that produces separate water and fat images as well as quantitative maps of fat signal fraction and T2* from complex multi-echo gradient recalled datasets. Accurate water and fat separation is challenging due to signal ambiguity at the voxel level. Whole-image optimization can resolve this ambiguity, but might be computationally demanding, especially for three-dimensional (3D) data. In this work, periodicity of the model fit residual as a function of the off-resonance was utilized to modify a previously proposed formulation of the problem. This gives a smaller solution space and allows rapid optimization. Feasibility and accurate separation of water and fat signal was demonstrated in breathhold 3D liver imaging of ten volunteer subjects, with both acquisition and reconstruction times below 20 seconds.

  • 106.
    Berglund, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Thunberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Is the rs10484561 SNP responsible for differences in age at diagnosis, transformation and death of patients with follicular lymphoma?2013In: International Journal of Hematologic Oncology, ISSN 2045-1407, Vol. 2, no 5, p. 391-396Article, review/survey (Refereed)
    Abstract [en]

    Aim:

    To analyze follicular lymphoma (FL) patients by determining the genotype at SNP rs10484561 (T or G) and comparing the polymorphism with overall survival, time to transformation, time from transformation to death, and age both dependently and independently of gender.

    Materials & methods:A total of 94 patients with FL diagnosed between 1970 and 2000 from a Swedish population were analyzed by PCR–restriction fragment length polymorphism to determine genotypes for rs10484561.

    Results:

    We found that women with FL and the TT genotype of SNP rs10484561 were older at diagnosis, transformation and when they died (p = 0.03, 0.01 and 0.02, respectively) and had a significantly shorter overall survival (p = 0.04) compared with women with the TG or GG genotypes.

    Conclusion:

    It is possible that the SNP rs10484561 polymorphism is responsible for differences in age at diagnosis, transformation and death for patients with follicular lymphoma, particularly in women.

  • 107.
    Berglund, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Thunberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    SNP rs6457327 is a predictor for overall survival in follicular lymphoma as well as survival after transformation2011In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, no 16, p. 4489-4489Article in journal (Refereed)
  • 108.
    Berglund, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Hedström, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Thunberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    High expression of microRNA-200c predicts poor clinical outcome in diffuse large B-cell lymphoma2013In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 29, no 2, p. 720-724Article in journal (Refereed)
    Abstract [en]

    Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of B-cell lymphomas. A new and important tool for understanding the biology and clinical course of DLBCL is microRNA expression. This study presents microRNA-200c expression data from 61 DLBCL patients treated with CHOP or R-CHOP. Patients with high microRNA-200c expression had a median survival of 20.3 months and a significantly shorter overall survival (P=0.019) compared to patients with low microRNA-200c expression, who had a median survival of 35.8 months. We also found that patients treated with R-CHOP only and displaying high microRNA-200c expression had a significantly shorter overall survival compared to patients with low microRNA-200c expression, where all patients were still alive at the time of the last follow-up (P=0.0036). Lastly, we found that patients with high microRNA-200c expression had a significantly shorter time from initial diagnosis to the first relapse compared to patients with low microRNA-200c expression (P=0.0001). To our knowledge, this is the first study showing that the expression of microRNA-200c affects the clinical outcome of DLBCL patients, and that microRNA-200c is involved in the biology of DLBCL development, although larger studies are necessary to confirm this. Further investigations may also help to elucidate the biological role of microRNA-200c in DLBCL.

  • 109.
    Berglund, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Zainuddin, N.
    Thunberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Is a TNF Alpha Polymorphism Responsible for Mutations in the TP53 Gene?2011In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 73, no 2, p. 154-155Article in journal (Refereed)
  • 110.
    Berglund, Åke
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Cedermark, B
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Is it deleterious to delay the start of adjuvant chemotherapy in colon cancer stage III?2008In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 19, no 2, p. 400-402Article in journal (Refereed)
  • 111.
    Berglund, Åke
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Willen, Linda
    Grodeberg, Lina
    Skattum, Lillemor
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Pauksens, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    The response to vaccination against influenza A(H1N1) 2009, seasonal influenza and Streptococcus pneumoniae in adult outpatients with ongoing treatment for cancer with and without rituximab2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 9, p. 1212-1220Article in journal (Refereed)
    Abstract [en]

    It is debated whether cancer patients treated with chemotherapy can mount an adequate response to vaccination. Material and methods. Ninety-six adult outpatients with cancer, who were undergoing chemotherapy and/or monoclonal antibody, tyrosine kinase inhibitor, irradiation or corticosteroid treatments, were studied. Two doses of the pandemic influenza A(H1N1)/09 AS03-adjuvanted split virion vaccine, one dose of the seasonal influenza vaccine and one dose of the 23-valent pneumococcal polysaccharide vaccine were given. Serum haemagglutination inhibition (HI) assays were used to determine antibody titres against the influenza strains. For the pneumococcal vaccine 14 different serotype-specific anti-capsular antibodies were measured by bead assay xMAP (R). Results. Patients treated with rituximab did not respond to vaccination. For patients without rituximab treatment 4% had putatively protective antibodies before vaccination (HI >= 40) to the pandemic-like strain A/California7/2009HINI. After the first and second dose of vaccine, seroprotection rates (SPR) were 62% and 87%, and seroconversion rates (SCR) 62% and 84%, respectively. Before seasonal flu vaccination SPR against influenza A/Brisbane/59/2007H1N1 and A/Uruguay/10/2007H3N2 were 19% and 17%, respectively. After vaccination, SPR were 70% and 59% and SCR 42% and 50%, respectively. For the pneumococcal vaccine protective antibodies were found to 40% of the 14 strains before and to 68% after vaccination. The mean response to pneumococcal vaccination was to 44% of the 14 serotypes. A response to at least 50% of the 14 serotypes was found in 49% of the patients. No serious adverse events were reported. Conclusion. A substantial number of adult cancer patients with ongoing chemotherapy treatment could mount an adequate serological response to influenza and pneumococcal vaccination without severe adverse events. Thus, vaccination should be recommended. Adjuvanted vaccines may improve the vaccine response among this patient group. Patients recently treated with rituximab do not respond to vaccination.

  • 112.
    Bergman, Antonina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Moore, Kevin
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Efficacy of the hepatocyte-specific contrast medium FP 736-04 for CT in two models of experimental diffuse liver disease1998In: Academic Radiology, ISSN 1076-6332, E-ISSN 1878-4046, Vol. 5, no Suppl 1, p. S13-S15; discussion S28-S30Article in journal (Refereed)
  • 113.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Akhter, Tansim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Plasma Levels of S100B in Preeclampsia and Association With Possible Central Nervous System Effects2014In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 27, no 8, p. 1105-1111Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    S100B is supposed to be a peripheral biomarker of central nervous system (CNS) injury. The purpose of this study was to compare levels of S100B in women with preeclampsia with levels in healthy pregnant control subjects and furthermore to analyze levels of S100B in relation to possible CNS effects.

    METHODS:

    A cross-sectional case-control study in antenatal care centers in Uppsala, Sweden, was performed. Fifty-three women with preeclampsia and 58 healthy pregnant women were recruited at similar gestational length; women with preeclampsia were recruited at time of diagnosis, and control subjects were recruited during their routine visit to an antenatal clinic. Plasma samples were collected, and levels of S100B were analyzed with an enzyme-linked immunosorbent assay. Information about demographic and clinical characteristics, including symptoms related to CNS affection, was collected from the medical records. The main outcome measures were plasma levels of S100B and possible CNS effects.

    RESULTS:

    Levels of S100B were significantly higher among women with preeclampsia than among control subjects (0.12 µg/L vs. 0.07 µg/L; P < 0.001). In preeclampsia, there was a significant association between high levels of S100B and visual disturbances (P < 0.05).

    CONCLUSIONS:

    S100B is increased among women with preeclampsia, and high levels of S100B associate with visual disturbances, which might reflect CNS affection in women with preeclampsia.

  • 114. Bergman, O.
    et al.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Linnman, Claes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Faria, Vanda
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bani, M.
    Pich, E. M.
    Bettica, P.
    Henningsson, S.
    Manuck, S. B.
    Ferrell, R. E.
    Nikolova, Y. S.
    Hariri, A. R.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Westberg, L.
    Eriksson, E.
    Association between amygdala reactivity and a dopamine transporter gene polymorphism2014In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 4, p. e420-Article in journal (Refereed)
    Abstract [en]

    Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3' untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotional stimuli. Amygdala reactivity was examined by comparing regional cerebral blood flow, measured with positron emission tomography and [O-15] water, during exposure to angry and neutral faces, respectively, in a Swedish sample comprising 32 patients with social anxiety disorder and 17 healthy volunteers. In a separate US sample, comprising 85 healthy volunteers studied with blood oxygen level-dependent functional magnetic resonance imaging, amygdala reactivity was assessed by comparing the activity during exposure to threatening faces and neutral geometric shapes, respectively. In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes. The results suggest that this polymorphism contributes to individual variability in amygdala reactivity.

  • 115.
    Bergman, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Estrada, Sergio
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Hall, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Rahman, Rashidur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Blomgren, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Larhed, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Svedberg, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Thibblin, Alf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Wångsell, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Synthesis and Labelling of a Piperazine-Based Library of 11C-Labeled Ligands for Imaging of the Vesicular Acetylcholine Transporter2014In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 57, no 8, p. 525-532Article in journal (Refereed)
    Abstract [en]

    The cholinergic system is involved in neurodegenerative diseases, and visualization of cholinergic innervations with positron emission tomography (PET) would be a useful tool in understanding these diseases. A ligand for the vesicular acetylcholine transporter (VAChT), acknowledged as a marker for cholinergic neurons, could serve as such a PET tracer. The aim was to find a VAChT PET tracer using a library concept to create a small but diverse library of labeled compounds. From the same precursor and commercially available aryl iodides 6a-f, six potential VAChT PET tracers, [C-11]-(+/-)5a-f, were C-11-labeled by a palladium (0)-mediated aminocarbonylation, utilizing a standard protocol. The labeled compounds [C-11]-(+/-)5a-f were obtained in radiochemical purities >95% with decay-corrected radiochemical yields and specific radioactivities between 4-25% and 124-597 GBq/mu mol, respectively. Autoradiography studies were then conducted to assess the compounds binding selectivity for VAChT. Labeled compounds [C-11]-(+/-)5d and [C-11]-(+/-)5e showed specific binding but not enough to permit further preclinical studies. To conclude, a general method for a facile synthesis and labeling of a small piperazine-based library of potential PET tracers for imaging of VAChT was shown, and in upcoming work, another scaffold will be explored using this approach.

  • 116.
    Bergqvist, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Ljungman, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Treatment options for abdominal aortic aneurysm (AAA)2007In: Vascular surgery / [ed] C.D. Liapsis, K. Baltzer, F. Benedetti-Valentini, J. Fernandes e Fernandes, Berlin Heidelberg New York: Springer , 2007, p. 325-329Chapter in book (Refereed)
  • 117. Bergström, Mats
    et al.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lindner, K J
    Bjurling, Pernilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    In vivo demonstration of enzyme activity in endocrine pancreatic tumors: decarboxylation of carbon-11-DOPA to carbon-11-dopamine1996In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 37, no 1, p. 32-37Article in journal (Refereed)
    Abstract [en]

    METHODS:

    We used PET to characterize the uptake and decarboxylation of 11C-L-DOPA in vivo in two patients with endocrine pancreatic tumors: one glucagonoma and one gastrinoma.

    RESULTS:

    With L-DOPA labeled with 11C in the beta position, in which the radioactive label follows the molecule through decarboxylation to dopamine, significant uptake was observed in the tumors. With L-DOPA labeled in the carboxyl group, in which the label is rapidly eliminated from the tissue as 11CO2 if decarboxylation takes place, an almost complete lack of uptake is noted.

    CONCLUSION:

    This study shows that, using selective position labeling, an in vivo action of enzymatic activity can be observed with PET and that significant decarboxylation occurs in the tested endocrine pancreatic tumors. Also, marked retention of radioactivity occurs after treatment with somatostatin analogs. It is hypothesized that this is a reflection of a reduction of exocytosis which is induced by this treatment.

  • 118. Bergström, Mats
    et al.
    Juhlin, Claes
    Bonasera, Tomas A
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Rastad, Jonas
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Långström, Bengt
    PET imaging of adrenal cortical tumors with the 11beta-hydroxylase tracer 11C-metomidate2000In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 41, no 2, p. 275-282Article in journal (Refereed)
    Abstract [en]

    The purpose of the study was to evaluate PET with the tracer 11C-metomidate as a method to identify adrenal cortical lesions.

    METHODS:

    PET with 11C-metomidate was performed in 15 patients with unilateral adrenal mass confirmed by CT. All patients subsequently underwent surgery, except 2 who underwent biopsy only. The lesions were histopathologically examined and diagnosed as adrenal cortical adenoma (n = 6; 3 nonfunctioning), adrenocortical carcinoma (n = 2), and nodular hyperplasia (n = 1). The remaining were noncortical lesions, including 1 pheochromocytoma, 1 myelolipoma, 2 adrenal cysts, and 2 metastases.

    RESULTS:

    All cortical lesions were easily identified because of exceedingly high uptake of 11C-metomidate, whereas the noncortical lesions showed very low uptake. High uptake was also seen in normal adrenal glands and in the stomach. The uptake was intermediate in the liver and low in other abdominal organs. Images obtained immediately after tracer injection displayed high uptake in the renal cortex and spleen. The tracer uptake in the cortical lesions increased throughout the examination. For quantitative evaluation of tracer binding in individual lesions, a model with the splenic radioactivity concentration assigned to represent nonspecific uptake was applied. Values derived with this method, however, did show the same specificity as the simpler standardized uptake value concept, with similar difference observed for cortical versus noncortical lesions.

    CONCLUSION:

    PET with 11C-metomidate has the potential to be an attractive method for the characterization of adrenal masses with the ability to discriminate lesions of adrenal cortical origin from noncortical lesions.

  • 119.
    Bergström, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Khan, Tanweera Shaheena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Juhlin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Bonasera, T.A.
    Fasth, K.-J.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    PET with [11C]-Metomidate for the Visualization of Adrenocortical Tumors and Discrimination from Other Lesions1999In: Clinical Positron Imaging, ISSN 1095-0397, E-ISSN 1878-5751, Vol. 2, no 6, p. 339-Article in journal (Refereed)
    Abstract [en]

    Purpose:

    The purpose of the study was to evaluate the potential role of PET with the adrenocortical-specific tracer 11C-metomidate in the characterization of incidentally found adrenal cortical lesions and in adrenocortical carcinomas.

    Methods:

    PET with 11C-metomidate was performed in 15 patients with unilateral adrenal mass confirmed by CT (incidentalomas) and in 9 additional patients with adrenocortical cancer. All incidentalomas subsequently underwent surgery, except 2 subjected to biopsy only. These lesions were histopathologically examined and diagnosed as adrenal cortical adenoma (n = 6; 3 nonfunctioning), adrenocortical carcinoma (n = 2) and nodular hyperplasia (n = 1). The remaining were non-cortical lesions including 1 pheochromocytoma, 1 myelolipoma, 2 adrenal cysts, and 2 metastases.

    Results:

    All lesions, except 1, with an adrenocortical origin were easily identified due to exceedingly high uptake of 11C-metomidate, whereas the non-cortical lesions showed very low uptake. The 1 false negative was a cancer that at surgery was found to be extensively necrotic. High uptake was also seen in normal adrenal glands. The tracer uptake kinetics indicated trapping of the tracer in the cortical lesions. For quantitative evaluation of tracer binding in individual lesions, the simple SUV concept was found to be equally accurate as more elaborate kinetic analyses.

    Conclusion:

    The patients presented and altogether over 40 PET investigations have demonstrated 11C-metomidate to be an attractive tracer for the characterization of adrenal masses with the ability to discriminate lesions of adrenal cortical origin from non-cortical lesions. Additionally the method allows the assessment of metastases from adrenocortical cancers, and the very high contrast has allowed partial whole-body examinations.

  • 120. Berndt, Sonja I.
    et al.
    Skibola, Christine F.
    Joseph, Vijai
    Camp, Nicola J.
    Nieters, Alexandra
    Wang, Zhaoming
    Cozen, Wendy
    Monnereau, Alain
    Wang, Sophia S.
    Kelly, Rachel S.
    Lan, Qing
    Teras, Lauren R.
    Chatterjee, Nilanjan
    Chung, Charles C.
    Yeager, Meredith
    Brooks-Wilson, Angela R.
    Hartge, Patricia
    Purdue, Mark P.
    Birmann, Brenda M.
    Armstrong, Bruce K.
    Cocco, Pierluigi
    Zhang, Yawei
    Severi, Gianluca
    Zeleniuch-Jacquotte, Anne
    Lawrence, Charles
    Burdette, Laurie
    Yuenger, Jeffrey
    Hutchinson, Amy
    Jacobs, Kevin B.
    Call, Timothy G.
    Shanafelt, Tait D.
    Novak, Anne J.
    Kay, Neil E.
    Liebow, Mark
    Wang, Alice H.
    Smedby, Karin E.
    Adami, Hans-Olov
    Melbye, Mads
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Chang, Ellen T.
    Glenn, Martha
    Curtin, Karen
    Cannon-Albright, Lisa A.
    Jones, Brandt
    Diver, W. Ryan
    Link, Brian K.
    Weiner, George J.
    Conde, Lucia
    Bracci, Paige M.
    Riby, Jacques
    Holly, Elizabeth A.
    Smith, Martyn T.
    Jackson, Rebecca D.
    Tinker, Lesley F.
    Benavente, Yolanda
    Becker, Nikolaus
    Boffetta, Paolo
    Brennan, Paul
    Foretova, Lenka
    Maynadie, Marc
    McKay, James
    Staines, Anthony
    Rabe, Kari G.
    Achenbach, Sara J.
    Vachon, Celine M.
    Goldin, Lynn R.
    Strom, Sara S.
    Lanasa, Mark C.
    Spector, Logan G.
    Leis, Jose F.
    Cunningham, Julie M.
    Weinberg, J. Brice
    Morrison, Vicki A.
    Caporaso, Neil E.
    Norman, Aaron D.
    Linet, Martha S.
    De Roos, Anneclaire J.
    Morton, Lindsay M.
    Severson, Richard K.
    Riboli, Elio
    Vineis, Paolo
    Kaaks, Rudolph
    Trichopoulos, Dimitrios
    Masala, Giovanna
    Weiderpass, Elisabete
    Chirlaque, Mara-Dolores
    Vermeulen, Roel C. H.
    Travis, Ruth C.
    Giles, Graham G.
    Albanes, Demetrius
    Virtamo, Jarmo
    Weinstein, Stephanie
    Clavel, Jacqueline
    Zheng, Tongzhang
    Holford, Theodore R.
    Offit, Kenneth
    Zelenetz, Andrew
    Klein, Robert J.
    Spinelli, John J.
    Bertrand, Kimberly A.
    Laden, Francine
    Giovannucci, Edward
    Kraft, Peter
    Kricker, Anne
    Turner, Jenny
    Vajdic, Claire M.
    Ennas, Maria Grazia
    Ferri, Giovanni M.
    Miligi, Lucia
    Liang, Liming
    Sampson, Joshua
    Crouch, Simon
    Park, Ju-Hyun
    North, Kari E.
    Cox, Angela
    Snowden, John A.
    Wright, Josh
    Carracedo, Angel
    Lopez-Otin, Carlos
    Bea, Silvia
    Salaverria, Itziar
    Martin-Garcia, David
    Campo, Elias
    Fraumeni, Joseph F., Jr.
    de Sanjose, Silvia
    Hjalgrim, Henrik
    Cerhan, James R.
    Chanock, Stephen J.
    Rothman, Nathaniel
    Slager, Susan L.
    Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 8, p. 868-U202Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.

  • 121. Bernhard, Juerg
    et al.
    Dietrich, Daniel
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bodoky, Gyoergy
    Scheithauer, Werner
    Herrmann, Richard
    Clinical Benefit Response in Pancreatic Cancer Trials Revisited2014In: Oncology Research and Treatment, ISSN 2296-5270, Vol. 37, no 1-2, p. 42-48Article in journal (Refereed)
    Abstract [en]

    Objectives: Clinical benefit response (CBR), based on changes in pain, Karnofsky performance status, and weight, is an established palliative endpoint in trials for advanced gastrointestinal cancer. We investigated whether CBR is associated with survival, and whether CBR reflects a wide-enough range of domains to adequately capture patients' perception. Methods: CBR was prospectively evaluated in an international phase III chemotherapy trial in patients with advanced pancreatic cancer (n = 311) in parallel with patient-reported outcomes (PROs). Results: The median time to treatment failure was 3.4 months (range: 0-6). The majority of the CBRs (n = 39) were noted in patients who received chemotherapy for at least 5 months. Patients with CBR (n = 62) had longer survival than non-responders (n = 182) (hazard ratio = 0.69; 95% confidence interval: 0.51-0.94; p = 0.013). CBR was predicted with a sensitivity and specificity of 77-80% by various combinations of 3 mainly physical PROs. A comparison between the duration of CBR (n = 62, median = 8 months, range = 4-31) and clinically meaningful improvements in the PROs (n = 100-116; medians = 9-11 months, range = 4-24) showed similar intervals. Conclusion: CBR is associated with survival and mainly reflects physical domains. Within phase III chemotherapy trials for advanced gastrointestinal cancer, CBR can be replaced by a PRO evaluation, without losing substantial information but gaining complementary information.

  • 122.
    Berntsson, Shala Ghaderi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Falk, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Savitcheva, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Godau, Andrea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Zetterling, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hesselager, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Perfusion and diffusion MRI combined with (11)C-methionine PET in the preoperative evaluation of suspected adult low-grade gliomas2013In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 114, no 2, p. 241-249Article in journal (Refereed)
    Abstract [en]

    Perfusion and diffusion magnetic resonance imaging (pMRI, dMRI) are valuable diagnostic tools for assessing brain tumors in the clinical setting. The aim of this study was to determine the correlation of pMRI and dMRI with (11)C-methionine positron emission tomography (MET PET) in suspected low-grade gliomas (LGG) prior to surgery. Twenty-four adults with suspected LGG were enrolled in an observational study and examined by MET PET, pMRI and dMRI. Histological tumor diagnosis was confirmed in 23/24 patients (18 gliomas grade II, 5 gliomas grade III). The maximum relative cerebral blood volume (rCBVmax) and the minimum mean diffusivity (MDmin) were measured in tumor areas with highest MET uptake (hotspot) on PET by using automated co-registration of MRI and PET scans. A clearly defined hotspot on PET was present in all 23 tumors. Regions with rCBVmax corresponded with hotspot regions in all tumors, regions with MDmin corresponded with hotspot regions in 20/23 tumors. The correlation between rCBVmax (r = 0.19, P = 0.38) and MDmin (r = -0.41, P = 0.053) with MET uptake in the hotspot was not statistically significant. Taken into account the difficulties of measuring perfusion abnormalities in non-enhancing gliomas, this study demonstrates that co-registered MET PET and pMRI facilitates the identification of regions with rCBVmax. Furthermore, the lack of a clear positive correlation between tumor metabolism in terms of MET uptake and tumor vascularity measured as rCBVmax suggests that combined pMRI/PET provides complementary baseline imaging data in these tumors.

  • 123.
    Beshara, Soheir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Långström, Bengt
    PET Centre, University Hospital, Uppsala, Sweden.
    Antoni, Gunnar
    PET Centre, University Hospital, Uppsala, Sweden.
    Danielsson, Bo G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Pharmacokinetics and red cell utilization of 52Fe/59Fe-labelled iron polymaltose in anaemic patients using positron emission tomography2003In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 120, no 5, p. 853-859Article in journal (Other academic)
    Abstract [en]

    Parenteral iron-polysaccharide complexes are increasingly applied. The pharmacokinetics of iron sucrose have been assessed by our group using positron emission tomography (PET). A single intravenous injection of 100 mg iron as iron (III) hydroxide-polymaltose complex, labelled with a tracer in the form of 52Fe/59Fe, was similarly assessed in six patients using PET for about 8 h. Red cell utilization was followed for 4 weeks. Iron polymaltose was similarly distributed to the liver, spleen and bone marrow. However, a larger proportion of this complex was rapidly distributed to the bone marrow. The shorter equilibration phase for the liver, about 25 min, indicates the minimal role of the liver for direct distribution. Splenic uptake also reflected the reticuloendothelial handling of this complex. Red cell utilization ranged from 61% to 99%. Despite the relatively higher uptake by the bone marrow, there was no saturation of marrow transport systems at this dose level. In conclusion, high red cell utilization of iron polymaltose occurred in anaemic patients. The major portion of the injected dose was rapidly distributed to the bone marrow. In addition, the reticuloendothelial uptake of this complex may reflect the safety of polysaccharide complexes. Non-saturation of transport systems to the bone marrow indicated the presence of a large interstitial transport pool, which might possibly be transferrin.

  • 124.
    Biglarnia, Ali-Reza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Bennet, William
    Nilsson, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Yamamoto, Shinji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Sedigh, Amir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    von Zur-Mühlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Bäckman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Utilization of Small Pediatric Donors Including Infants for Pancreas and Kidney Transplantation: Exemplification of the Surgical Technique and the Surveillance2014In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 260, no 2, p. e5-7Article in journal (Refereed)
  • 125.
    Biglarnia, Ali-Reza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Nilsson, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    von Zur-Mühlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Wagner, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO-incompatible pancreas and kidney transplantation2011In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 24, no 8, p. e61-e66Article in journal (Refereed)
    Abstract [en]

    We describe the presumably first intentional ABO-incompatible deceased-donor kidney and pancreas transplantation with a severe antibody-mediated rejection during a rebound of isoagglutinins. Rejection was successfully treated with eculizumab, which inhibits the terminal pathway of complement. Complement analysis (C3, C3d,g, and a modified assay of classical complement-related hemolytic function) documented complement activation and confirmed that eculizumab completely blocked complement function. At 6 months, the patient had normal kidney and pancreas function, and histological evaluations revealed no evidence of sustained graft damage. This successful transplantation suggests that ABO barriers can safely be overcome without extensive preconditioning, when the complement inhibitor eculizumab is included.

  • 126.
    Billström, Gry Hulsart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Piskounova, Sonya
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Bowden, Tim
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Improved bone formation by altering surface area of hyaluronan-based hydrogel carrier for bone morphogenetic protein-22012In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, p. S114-S114Article in journal (Other academic)
  • 127.
    Birgisson, Helgi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Wallin, Ulrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Survival endpoints in colorectal cancer and the effect of second primary other cancer on disease free survival2011In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 11, p. 438-Article in journal (Refereed)
    Abstract [en]

    Background: In cancer research the selection and definitions of survival endpoints are important and yet they are not used consistently. The aim of this study was to compare different survival endpoints in patients with primary colorectal cancer (CRC) and to understand the effect of second primary other cancer on disease-free survival (DFS) calculations.

    Methods: A population-based cohort of 415 patients with CRC, 332 of whom were treated with curative intention between the years 2000-2003, was analysed. Events such as locoregional recurrence, distant metastases, second primary cancers, death, cause of death and loss to follow-up were recorded. Different survival endpoints, including DFS, overall survival, cancer-specific survival, relapse-free survival, time to treatment failure and time to recurrence were compared and DFS was calculated with and without inclusion of second primary other cancers.

    Results: The events that occurred most often in patients treated with curative intention were non-cancer-related death (n = 74), distant metastases (n = 66) and death from CRC (n = 59). DFS was the survival endpoint with most events (n = 170) followed by overall survival (n = 144) and relapse-free survival (n = 139). Fewer events were seen for time to treatment failure (n = 80), time to recurrence (n = 68) and cancer-specific survival (n = 59). Second primary other cancer occurred in 26 patients and its inclusion as an event in DFS calculations had a detrimental effect on the survival. The DFS for patients with stage I-III disease was 62% after 5 years if second primary other cancer was not included as an event, compared with 58% if it was. However, the difference was larger for stage II (68 vs 60%) than for stage III (49 vs 47%).

    Conclusions: The inclusion of second primary other cancer as an endpoint in DFS analyses significantly alters the DFS for patients with CRC. Researchers and journals must clearly define survival endpoints in all trial protocols and published manuscripts.

  • 128.
    Bjermo, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Iggman, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Dahlman, Ingrid
    Karolinska Institutet, Department of Medicine.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Persson, Lena
    Karolinska Institutet, Department of Endocrinology, Metabolism and Diabetes.
    Berglund, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Pulkki, Kari
    University of Eastern Finland, Department of Clinical Chemistry and Eastern Finland Laboratory Centre.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Uusitupa, Matti
    University of Eastern Finland, Institute of Public Health and Clinical Nutrition, Clinical Nutrition.
    Rudling, Mats
    Karolinska Institutet, Department of Endocrinology, Metabolism and Diabetes.
    Arner, Peter
    Karolinska Institutet, Department of Medicine.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Dietary fat modification and liver fat content in abdominal obesityManuscript (preprint) (Other academic)
  • 129.
    Bjermo, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Iggman, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Center for Clinical Research Dalarna.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Dahlman, Ingrid
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Persson, Lena
    Berglund, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Pulkki, Kari
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Uusitupa, Matti
    Rudling, Mats
    Arner, Peter
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial2012In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 95, no 5, p. 1003-1012Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Replacing SFAs with vegetable PUFAs has cardiometabolic benefits, but the effects on liver fat are unknown. Increased dietary n-6 PUFAs have, however, also been proposed to promote inflammation-a yet unproven theory.

    OBJECTIVE:

    We investigated the effects of PUFAs on liver fat, systemic inflammation, and metabolic disorders.

    DESIGN:

    We randomly assigned 67 abdominally obese subjects (15% had type 2 diabetes) to a 10-wk isocaloric diet high in vegetable n-6 PUFA (PUFA diet) or SFA mainly from butter (SFA diet), without altering the macronutrient intake. Liver fat was assessed by MRI and magnetic resonance proton (1H) spectroscopy (MRS). Proprotein convertase subtilisin/kexin type-9 (PCSK9, a hepatic LDL-receptor regulator), inflammation, and adipose tissue expression of inflammatory and lipogenic genes were determined.

    RESULTS:

    A total of 61 subjects completed the study. Body weight modestly increased but was not different between groups. Liver fat was lower during the PUFA diet than during the SFA diet [between-group difference in relative change from baseline; 16% (MRI; P < 0.001), 34% (MRS; P = 0.02)]. PCSK9 (P = 0.001), TNF receptor-2 (P < 0.01), and IL-1 receptor antagonist (P = 0.02) concentrations were lower during the PUFA diet, whereas insulin (P = 0.06) tended to be higher during the SFA diet. In compliant subjects (defined as change in serum linoleic acid), insulin, total/HDL-cholesterol ratio, LDL cholesterol, and triglycerides were lower during the PUFA diet than during the SFA diet (P < 0.05). Adipose tissue gene expression was unchanged.

    CONCLUSIONS:

    Compared with SFA intake, n-6 PUFAs reduce liver fat and modestly improve metabolic status, without weight loss. A high n-6 PUFA intake does not cause any signs of inflammation or oxidative stress. Downregulation of PCSK9 could be a novel mechanism behind the cholesterol-lowering effects of PUFAs.

  • 130.
    Bjerner, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ericsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nilsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Hemmingsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Evaluation of nonperfused myocardial ischemia with MRI and an intravascular USPIO contrast agent in an ex vivo pig model2000In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 12, no 6, p. 866-872Article in journal (Refereed)
    Abstract [en]

    The ultrasmall superparamagnetic iron oxide (USPIO) preparation NC100150 Injection (Clariscan; Nycomed Imaging, Oslo, Norway) was tested for its ability to delineate nonperfused myocardium under steady-state conditions. An experimental animal model of focal myocardial ischemia induced by ligation of the distal part of the left anterior descending artery was used. The contrast agent was administered in four doses: 0, 4, 8, and 12 mg Fe/kg body weight. Magnetic resonance examination ex vivo, including T1-, T2-, and T2*-weighted sequences, was performed. Nonperfused myocardium was determined by fluorescein. The best delineation of nonperfused myocardium was found with a T1-weighted inversion recovery/turbo spin-echo sequence and doses of 4 and 8 mg Fe/kg body weight, where 95% of the volume was discernible at the dose of 4 mg Fe/kg body weight. The results suggest that steady-state imaging by T1-weighted sequence with the use of NC100150 Injection to delineate nonperfused myocardium is feasible. J. Magn. Reson. Imaging 2000;12:866-872.

  • 131.
    Bjerner, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ericsson, Anders
    Wikström, Gerhard
    Hemmingsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    First-Pass Myocardial Perfusion MR Imaging with Outer-Volume Suppression and the Intravascular Contrast Agent NC100150 Injection: Preliminary Results in Eight Patients.2001In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 221, no 3, p. 822-826Article in journal (Refereed)
    Abstract [en]

    The authors evaluated the feasibility of combining single-shot T2-weighted turbo spin-echo magnetic resonance (MR) imaging and first-pass myocardial perfusion MR imaging with an intravascular ultrasmall superparamagnetic iron oxide (USPIO) contrast agent, NC100150 Injection (3 mg of iron per kilogram of body weight). Eight patients with coronary vessel disease underwent T2-weighted turbo spin-echo MR imaging (in-plane resolution, 1-2 mm) during the first pass of the USPIO contrast agent. The mean decrease in signal intensity in myocardium perfused by a nonstenotic coronary artery was 59% +/- 13 (SD) (P < .012) This method is feasible for imaging of myocardial perfusion.

  • 132.
    Bjerner, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Haglund, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    3D surface rendering of images from multiple MR pulse sequences in the pre-operative evaluation of hepatic lesions1998In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 39, no 6, p. 698-700Article in journal (Refereed)
    Abstract [en]

    Segmentation and reconstruction took 1-2 h. To be able to combine the volumes from the different data sets, certain criteria had to be fulfilled: a) the field of view had to be constant; b) the same volume had to be scanned every time which meant that the slice thickness and the number of slices could be adjusted as long as the volume covered was the same; and c) the positioning of each volume had to be identical between every scan. The resulting 3D reconstruction gave the surgeon a clear appreciation of the different lesions and their relation to the different liver segments in the pre-operative planning of hepatic resections.

  • 133.
    Bjerner, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ericsson, Anders
    Briley-Soebo, Karen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bjørnerud, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    In and ex vivo MR evaluation of acute myocardial ischemia in pigs by determining R1 in steady state after the administration of the intravascular contrast agent NC100150 injection2004In: Investigative Radiology, ISSN 0020-9996, E-ISSN 1536-0210, Vol. 39, no 8, p. 479-486Article in journal (Refereed)
  • 134.
    Bjerner, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    High in-plane resolution T2-weighted magnetic resonance imaging of acute myocardial ischemia in pigs using the intravascular contrast agent NC100150 injection.2004In: Investigative Radiology, ISSN 0020-9996, E-ISSN 1536-0210, Vol. 39, no 8, p. 470-478Article in journal (Refereed)
    Abstract [en]

    Rationale and Objectives: The intravascular contrast agent NC100150 injection was tested for its ability to demarcate nonperfused myocardium in a porcine model of coronary occlusion.

    Materials and Methods: A T2-weighted fast spin echo sequence was acquired ex vivo and in vivo during first pass and steady-state circulation of the contrast agent in 2 dosages (2 and 5 mg Fe/kg bw) or saline.

    Results: Ex vivo, in the high-dose group, the volume of nonperfused myocardium determined from T2-weighted images was 99% of that determined from photographs where perfused myocardium stained with fluorescein. A significantly higher contrast to noise ratio between perfused and nonperfused myocardium was found (both ex and in vivo in steady state) compared with the control group. During first pass, a significant reduction in signal intensity (74 ± 18%) was found in perfused myocardium after contrast injection.

    Conclusion: NC100150 injection, combined with T2-weighted turbo spin echo imaging, allowed detailed visualization of non-perfused myocardium in the steady state, which corresponded to the area at risk as determined by fluorescein.

  • 135.
    Bjersand, Kathrine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Poromaa, Inger Sundström
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Pseudomyxoma Peritone: symptoms, treatment, prognosis and sensitivity to cytostatic drugs in vitro2012In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 91, no S159, p. 71-71Article in journal (Other academic)
  • 136.
    Björk, Marcus
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Berglund, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Stoica, Peter
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Systems and Control. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Automatic control.
    Signal Modeling and the Cramér-Rao Bound for Absolute Magnetic Resonance Thermometry in Fat Tissue2011In: Proc. 45th Asilomar Conference on Signals, Systems, and Computers, 2011, p. 80-84Conference paper (Refereed)
    Abstract [en]

    Magnetic Resonance Imaging of tissues with both fat and water resonances allows for absolute temperature mapping through parametric modeling. The fat resonance is used as a reference to determine the absolute water resonance frequency which is linearly related to the temperature. The goal of thispaper is to assess whether or not resonance frequency based absolute temperature mapping is feasible in fat tissue. This is done by examining identifiability conditions and analyzing the obtainable performance in terms of the Cramér-Rao Bound of the temperature estimates. We develop the model by including multiple fat peaks, since even small fat resonances can be significant compared to the small water component in fat tissue. It is showed that a high signal to noise ratio is needed for practical use on a 1.5 T scanner, and that higher field strengths can improve the bound significantly. It is also shown that the choice of sampling interval is important to avoid aliasing. In sum, this type of magnetic resonance thermometry is feasible for fat tissuein applications where high field strength is used or when high signal to noise ratio can be obtained.

  • 137.
    Björkelund, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Novel Methods for Analysis of Heterogeneous Protein-Cell Interactions: Resolving How the Epidermal Growth Factor Binds to Its Receptor2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]