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  • 1.
    Alemany, Montserrat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Stenborg, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Terent, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sonninen, Pirkko
    Röntgenavdelningen, Åbo universitetssjukhus, Åbo, Finland.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Coexistence of microhemorrhages and acute spontaneous brain hemorrhage: correlation with signs of microangiopathy and clinical data2006In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 238, no 1, p. 240-7Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate prospectively with magnetic resonance (MR) imaging the coexistence of microhemorrhages (MHs) in white patients with acute spontaneous intraparenchymal hemorrhage (IPH) and acute ischemic stroke and to study the association with imaging findings of microangiopathy and various clinical data. MATERIALS AND METHODS: Before examinations, informed consents were signed by either the patient or a relative. The study was carried out with the approval of the local ethics committee. MR imaging was performed in 90 patients with acute stroke: 45 with acute spontaneous IPHs (24 men and 21 women; median age, 65 and 68 years, respectively) and 45 age-matched control subjects without intracranial hemorrhages (26 men and 19 women; median age for both, 67 years), as determined at computed tomography. MR imaging included transverse T1- and T2-weighted spin-echo, transverse fluid-attenuated inversion recovery, transverse and coronal T2*-weighted gradient-echo, and, in 50 patients, diffusion-weighted sequences. Presence of MHs and signs of microangiopathy, such as T2 hyperintensities or lacunae, were recorded in the white and deep gray matter. The relationships between MH and IPH and between MH and T2 hyperintensities were analyzed by means of regression analysis. Different clinical features, such as arterial hypertension or diabetes, were registered and correlated with the image findings by means of regression analysis. RESULTS: MHs were found in 64% of patients with IPH (29 of 45) and 18% of control subjects (eight of 45). A statistically significant relationship between MH and IPH was determined (P < .001). Among the 29 patients with IPH and MH, 24 (83%) had T2 hyperintensities and 13 (45%) had lacunae; among the 16 patients without MH, seven (44%) had T2 hyperintensities and three (19%) had lacunae. A relationship between MH and occurrence and extent of T2 hyperintensities was also identified (P < .001). There was no clear relationship with the clinical data studied. CONCLUSION: The results support a correlation between the presence of imaging signs of cerebral microangiopathy, clinically silent MHs, and acute IPHs. RSNA, 2006.

  • 2. Alexanderson, Camilla
    et al.
    Stener-Victorin, Elisabet
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Nilsson, Staffan
    Levin, Max
    Cajander, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Lönn, Lars
    Lönn, Malin
    Holmäng, Agneta
    A single early postnatal estradiol injection affects morphology and gene expression of the ovary and parametrial adipose tissue in adult female rats2010In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 122, no 1-3, p. 82-90Article in journal (Refereed)
    Abstract [en]

    Events during early life can affect reproductive and metabolic functions in adulthood. We evaluated the programming effects of a single early postnatal estradiol injection (within 3h after birth) in female rats. We assessed ovarian and parametrial adipose tissue morphology, evaluated gene expression related to follicular development and adipose tissue metabolism, and developed a non-invasive volumetric estimation of parametrial adipose tissue by magnetic resonance imaging. Estradiol reduced ovarian weight, increased antral follicle size and number of atretic antral follicles, and decreased theca interna thickness in atretic antral follicles. Adult estradiol-injected rats also had malformed vaginal openings and lacked corpora lutea, confirming anovulation. Estradiol markedly reduced parametrial adipose tissue mass. Adipocyte size was unchanged, suggesting reduced adipocyte number. Parametrial adipose tissue lipoprotein lipase activity was increased. In ovaries, estradiol increased mRNA expression of adiponectin, complement component 3, estrogen receptor alpha, and glucose transporter 3 and 4; in parametrial adipose tissue, expression of complement component 3 was increased, expression of estrogen receptor alpha was decreased, and expression of leptin, lipoprotein lipase, and hormone-sensitive lipase was unaffected. These findings suggest that early postnatal estradiol exposure of female rats result in long-lasting effects on the ovary and parametrial adipose tissue at adult age.

  • 3.
    Almqvist, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Targeted Therapy of Colorectal Cancer: Preclinical Evaluation of a Radiolabelled Antibody2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Targeted radiotherapy (TRT) of cancer is a promising approach that enables selective treatment of tumour cells, while sparing normal tissue. The humanized monoclonal antibody A33 (huA33) is a potential targeting agent for TRT of colorectal cancer, since its antigen is expressed in more than 95 % of all colorectal carcinomas. The aim of this thesis was to evaluate the therapeutic potential of the two huA33-based TRT-conjugates, 177Lu-huA33, and 211At-huA33.

    The conjugates 177Lu-huA33, and 211At-huA33, bound specifically to colorectal cancer cells, both in vitro and in vivo. A dose dependent cytotoxic effect of 211At-huA33 was also demonstrated in vitro. From a therapeutic perspective, both conjugates had a favourable biodistribution in tumour-bearing nude mice, with high tumour uptake and a low uptake in normal organs (with the exception of an expected thyroid uptake of 211At). After injection of 211At-huA33, the blood absorbed a slightly higher dose than the tumour, but for 177Lu-huA33, the tumour received a 12 times higher dose than blood. Two days after intravenous injection of 177Lu-huA33 in tumour-bearing mice, the tumours could be clearly visualised by gamma camera imaging, with very low interference from normal tissue radioactivity. In an experimental therapy study, also performed in tumour-bearing mice, there was an excellent therapeutic effect of 177Lu-huA33. About 50 % of the treated animals were tumour free 140 days after injection of 177Lu-huA33, while none of the non-radioactive controls survived beyond 20 days after injection of treatment substances.

    In conclusion, this thesis demonstrates that the therapeutic conjugates 177Lu-huA33, and 211At-huA33, are promising targeting agents that might help improve therapy of colorectal cancer.

    List of papers
    1.
    The record could not be found. The reason may be that the record is no longer available or you may have typed in a wrong id in the address field.
    2. Biodistribution of At-211-Labeled humanized monoclonal antibody A33
    Open this publication in new window or tab >>Biodistribution of At-211-Labeled humanized monoclonal antibody A33
    Show others...
    2007 (English)In: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, E-ISSN 1557-8852, Vol. 22, no 4, p. 480-487Article in journal (Refereed) Published
    Abstract [en]

    Radioimmunotherapy (RIT) could be a possible adjuvant treatment method for patients with colorectal carcinoma. The A33 antigen is a promising RIT target, as it is highly and homogenously expressed in 95% of all colorectal carcinomas. In this study, the humanized monoclonal antibody A33 (huA33), targeting the A33 antigen, was labeled with the therapeutic nuclide 211At, and the biodistribution and in vivo targeting ability of the conjugate was investigated in an athymic mouse xenograft model. There was an accumulation of 211At in tumor tissue over time, but no substantial accumulation was seen in any organ apart from the skin and thyroid, indicating no major release of free 211At in vivo. At all time points, the uptake of 211At-huA33 was higher in tumor tissue than in most organs, and at 8 hours postinjection (p.i.), no organ had a higher uptake than tumor tissue. The tumor-to-blood ratio of 211At-huA33 increased with time, reaching 2.5 after 21 hours p.i. The highest absorbed dose was found in the blood, but the tumor received a higher dose than any organ other than the thyroid. An in vivo blocking experiment showed that 211At-huA33 binds specifically to human tumor xenografts in athymic mice. In conclusion, the favorable biodistribution and specific in vivo targeting ability of 211At-huA33 makes it a potential therapeutic agent for the RIT of metastatic colorectal carcinoma.

    Keywords
    A33, monoclonal antibody, At-211, radioimmunotherapy, biodistribution
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-17038 (URN)10.1089/cbr.2007.349 (DOI)000249320800003 ()17803442 (PubMedID)
    Available from: 2008-06-16 Created: 2008-06-16 Last updated: 2017-12-08Bibliographically approved
    3. In vitro and in vivo characterization of 177Lu‑huA33: A radioimmunoconjugate against colorectal cancer
    Open this publication in new window or tab >>In vitro and in vivo characterization of 177Lu‑huA33: A radioimmunoconjugate against colorectal cancer
    Show others...
    2006 (English)In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 33, no 8, p. 991-998Article in journal (Refereed) Published
    Abstract [en]

    INTRODUCTION: The humanized monoclonal antibody A33 (huA33) is a potential targeting agent against colorectal carcinoma since the A33 antigen is highly and homogenously expressed in >95% of all colorectal cancers, both primary tumors and metastases. The aim of this study was to determine the biodistribution and tumor-targeting ability of (177)Lu-labeled huA33. METHODS: huA33 was labeled with the beta-emitting therapeutic nuclide (177)Lu using the chelator CHX-A"-DTPA, and the properties of the (177)Lu-CHX-A"-huA33 ((177)Lu-huA33) conjugate was determined both in vitro and in vivo in a biodistribution study in nude mice xenografted with colorectal SW1222 tumor cells. RESULTS: The (177)Lu-huA33 conjugate bound specifically to colorectal cancer cells in vitro (with a K(D) value of 2.3+/-0.3 nM, determined by a saturation assay) and in vivo. The tumor uptake of (177)Lu-huA33 was very high, peaking at 134+/-21%ID/g 72 h postinjection (pi). Normal tissue uptake was low; radioactivity concentration in blood (which had the second highest radioactivity concentration) was lower than in tumor at all time points studied (8 h to 10 days). The tumor-to-blood ratio increased with time, reaching 70+/-30, 10 days pi. Throughout the study, the uptake of (177)Lu in bone (known to accumulate free (177)Lu) was low, and the fraction of protein-bound (177)Lu in plasma samples was high (95% to 99%). This indicates high stability of the (177)Lu-huA33 conjugate in vivo. CONCLUSION: The (177)Lu-huA33 conjugate shows a very favorable biodistribution, with an impressively high tumor uptake and high tumor-to-organ ratios, indicating that the conjugate may be suitable for radioimmunotherapy of colorectal cancer.

    Keywords
    Antibody, A33 antigen, 177Lu, Colorectal cancer
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-97087 (URN)10.1016/j.nucmedbio.2006.09.003 (DOI)000242840500007 ()17127172 (PubMedID)
    Available from: 2008-04-23 Created: 2008-04-23 Last updated: 2017-12-14Bibliographically approved
    4. Therapy of colorectal cancer xenografts in nude mice using 177Lu labelled humanized antibody A33
    Open this publication in new window or tab >>Therapy of colorectal cancer xenografts in nude mice using 177Lu labelled humanized antibody A33
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-97088 (URN)
    Available from: 2008-04-23 Created: 2008-04-23 Last updated: 2010-01-13Bibliographically approved
  • 4.
    Almqvist, Ylva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Orlova, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Sjöström, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Jensen, Holger J.
    Danmark.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    In vitro characterization of 211 At-labeled antibody A33: a potential therapeutic agent against metastatic colorectal carcinoma2005In: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, E-ISSN 1557-8852, Vol. 20, no 5, p. 514-523Article in journal (Refereed)
    Abstract [en]

    The humanized antibody A33 binds to the A33 antigen, expressed in 95% of primary and metastatic colorectal carcinomas. The restricted pattern of expression in normal tissue makes this antigen a possible target for radioimmunotherapy of colorectal micrometastases. In this study, the A33 antibody was labeled with the therapeutic nuclide 211At using N-succinimidyl para-(tri-methylstannyl)benzoate (SPMB). The in vitro characteristics of the 211At-benzoate-A33 conjugate (211At-A33) were investigated and found to be similar to those of 125I-benzoate-A33 (125I-A33) in different assays. Both conjugates bound with high affinity to SW1222 cells (Kd = 1.7 ± 0.2 nM, and 1.8 ± 0.1 nM for 211At-A33 and 125I-A33, respectively), and both showed good intracellular retention (70% of the radioactivity was still cell associated after 20 hours). The cytotoxic effect of 211At-A33 was also confirmed. After incubation with 211At-A33, SW1222 cells had a survival of approximately 0.3% when exposed to some 150 decays per cell (DPC). The cytotoxic effect was found to be dose-dependent, as cells exposed to only 56 DPC had a survival of approximately 5%. The 211At-A33 conjugate shows promise as a potential radioimmunotherapy agent for treatment of micrometastases originating from colorectal carcinoma.

  • 5.
    Almqvist, Ylva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Steffen, Ann-Charlott
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Jensen, Holger
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. 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 Oncology, Radiology and Clinical Immunology, Radiology.
    Biodistribution of At-211-Labeled humanized monoclonal antibody A332007In: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, E-ISSN 1557-8852, Vol. 22, no 4, p. 480-487Article in journal (Refereed)
    Abstract [en]

    Radioimmunotherapy (RIT) could be a possible adjuvant treatment method for patients with colorectal carcinoma. The A33 antigen is a promising RIT target, as it is highly and homogenously expressed in 95% of all colorectal carcinomas. In this study, the humanized monoclonal antibody A33 (huA33), targeting the A33 antigen, was labeled with the therapeutic nuclide 211At, and the biodistribution and in vivo targeting ability of the conjugate was investigated in an athymic mouse xenograft model. There was an accumulation of 211At in tumor tissue over time, but no substantial accumulation was seen in any organ apart from the skin and thyroid, indicating no major release of free 211At in vivo. At all time points, the uptake of 211At-huA33 was higher in tumor tissue than in most organs, and at 8 hours postinjection (p.i.), no organ had a higher uptake than tumor tissue. The tumor-to-blood ratio of 211At-huA33 increased with time, reaching 2.5 after 21 hours p.i. The highest absorbed dose was found in the blood, but the tumor received a higher dose than any organ other than the thyroid. An in vivo blocking experiment showed that 211At-huA33 binds specifically to human tumor xenografts in athymic mice. In conclusion, the favorable biodistribution and specific in vivo targeting ability of 211At-huA33 makes it a potential therapeutic agent for the RIT of metastatic colorectal carcinoma.

  • 6.
    Almqvist, Ylva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Steffen, Ann-Charlott
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Divgi, Chaitanya R.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    In vitro and in vivo characterization of 177Lu‑huA33: A radioimmunoconjugate against colorectal cancer2006In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 33, no 8, p. 991-998Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The humanized monoclonal antibody A33 (huA33) is a potential targeting agent against colorectal carcinoma since the A33 antigen is highly and homogenously expressed in >95% of all colorectal cancers, both primary tumors and metastases. The aim of this study was to determine the biodistribution and tumor-targeting ability of (177)Lu-labeled huA33. METHODS: huA33 was labeled with the beta-emitting therapeutic nuclide (177)Lu using the chelator CHX-A"-DTPA, and the properties of the (177)Lu-CHX-A"-huA33 ((177)Lu-huA33) conjugate was determined both in vitro and in vivo in a biodistribution study in nude mice xenografted with colorectal SW1222 tumor cells. RESULTS: The (177)Lu-huA33 conjugate bound specifically to colorectal cancer cells in vitro (with a K(D) value of 2.3+/-0.3 nM, determined by a saturation assay) and in vivo. The tumor uptake of (177)Lu-huA33 was very high, peaking at 134+/-21%ID/g 72 h postinjection (pi). Normal tissue uptake was low; radioactivity concentration in blood (which had the second highest radioactivity concentration) was lower than in tumor at all time points studied (8 h to 10 days). The tumor-to-blood ratio increased with time, reaching 70+/-30, 10 days pi. Throughout the study, the uptake of (177)Lu in bone (known to accumulate free (177)Lu) was low, and the fraction of protein-bound (177)Lu in plasma samples was high (95% to 99%). This indicates high stability of the (177)Lu-huA33 conjugate in vivo. CONCLUSION: The (177)Lu-huA33 conjugate shows a very favorable biodistribution, with an impressively high tumor uptake and high tumor-to-organ ratios, indicating that the conjugate may be suitable for radioimmunotherapy of colorectal cancer.

  • 7.
    Almqvist, Ylva
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Tolmachev, Vladimir
    Lundqvist, Hans
    Sundin, Anders
    Therapy of colorectal cancer xenografts in nude mice using 177Lu labelled humanized antibody A33Manuscript (Other academic)
  • 8.
    Alparslan, Leyla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Chiodo, Christopher P.
    Lateral ankle instability: MR imaging of associated injuries and surgical treatment procedures2008In: Seminars in Musculoskeletal Radiology, ISSN 1089-7860, E-ISSN 1098-898X, Vol. 12, no 4, p. 346-58Article in journal (Refereed)
    Abstract [en]

    Chronic ankle instability has been defined as the development of recurrent ankle sprains and persistent symptoms after initial lateral ankle sprain. The diagnosis of ankle instability is usually established on the patient's history, physical examination, and radiographic assessment. Patients have signs of both functional and mechanical instability, and the repetitive, chronic nature of the injury may lead to intra-articular and periarticular pathologies. This article discusses the incidence, etiology, and magnetic resonance (MR) imaging of these pathologies, reviews the surgical treatment procedures for lateral ankle instability, and presents the postoperative MR imaging findings.

  • 9.
    Amini, Hashem
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Raiend, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    The Clinical Impact of Fetal Magnetic Resonance Imaging on Management of CNS Anomalies in the Second Trimester of Pregnancy2010In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 89, no 12, p. 20p. 1571-1581Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate the additional information of second trimester magnetic resonance imaging (MRI) compared to ultrasound in fetuses with identified or suspected CNS anomalies and to study the clinical impact of the information on pregnancy management.

    Design: Prospective study during 2004-2007. The fetal MRI examination was planned to be performed within three days after the ultrasound.

    Setting: Uppsala University hospital.    

    Subjects: Twenty-nine pregnant women where second trimester ultrasound identified or suspected fetal CNS anomalies.

    Main outcome measures: Evaluation of the additional information gained from MRI and the consequence it had on pregnancy management.

    Results: The mean interval between ultrasound and MRI was 1.6 days (range 0 –7). In 18 fetuses (62 %)  MRI verified the ultrasound diagnosis but provided no additional information, while in 8 (28 %) MRI gave additional information without changing the management. In 3 (10 %), MRI provided additional information that changed the management of the pregnancy. Two of these women were obese.

    Conclusions: Fetal MRI in the second trimester might be a clinically valuable adjunct to ultrasound for the evaluation of CNS anomalies, especially when ultrasound is inconclusive due to maternal obesity.

     

  • 10.
    Amini, Hashem
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. 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 Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    The Clinical Impact of Fetal Magnetic Resonance Imaging on Management of Non-CNS Anomalies in the Second Trimester of PregnancyManuscript (preprint) (Other academic)
    Abstract [en]

    Objectives: To evaluate the additional information of second trimester MRI compared to ultrasound in fetuses with identified or suspected non-CNS anomalies and to study the clinical impact of the MRI information on pregnancy management.

    Methods: Sixty-three women were included, where the second trimester ultrasound identified or raised suspicion of fetal anomalies. Ultrasound was compared to MRI in relation to the final diagnosis, fetal autopsy if performed or postnatal diagnosis. The additional information of MRI and effect on pregnancy management was estimated in consensus.

    Results: The mean gestational age at the last ultrasound before MRI was 18+1 weeks (range 13+0-21+5). The mean interval between ultrasound and MRI was 2.6 days (range 0-15). In 42 (67 %) cases MRI was performed within three days. All MRI examinations were assessable. In 43 (68 %) fetuses MRI provided no additional information, in 17 (27 %) MRI added information without changing the management and in three (5 %) MRI provided additional information which changed the management. These three cases had all oligohydramnios. In all six cases of diaphragmatic hernia MRI provided additional information.

    Conclusions: Fetal MRI of non-CNS anomalies is feasible in the second trimester and gives additional information in nearly a third of cases. It may provide a clinically valuable adjunct to ultrasound especially in cases of diaphragmatic hernia or oligohydramnios.

  • 11. Andrae, B.
    et al.
    Eriksson, L. G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Skoog, G.
    Anti-shock trousers (MAST) and transcatheter embolization in the management of massive obstetrics hemorrhage: A report of two cases1999In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 78, no 8, p. 740-741Article in journal (Refereed)
  • 12.
    Bajic, Dragan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Radiological Studies on Hippocampal Development: Morphological Variants and their Relationship to Epilepsy2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    During fetal development, the hippocampal structures are folded forming the hippocampal sulcus which penetrates into the temporal lobe and then the entity rotates.  During this process, the hippocampal sulcus will be closed and the inverted hippocampus takes a rounded form. After complete inversion, the hippocampus has an oval form in a plane perpendicular to its long axis. If this process has not been completed the hippocampus remains the rounded form. That condition is called incomplete hippocampal inversion (IHI).

    The aims of this study was to evaluate the frequency of IHI in non-epileptic and epileptic children and adults and to explore the development of the hippocampal region by studying premature neonates and fetuses.

    Magnetic resonance (MR) images of 201 epilepsy patients and 150 non-epileptic subjects were evaluated without knowing clinical data. IHI was found in 19 % in seizure free controls (20 left-sided and 8 bilateral). 30% of the 201 epilepsy patients had IHI (40 left-sided, 4 right-sided, 16 bilateral). The difference was statistically significant (p<0.02). 25% of the temporal lobe epilepsy patients had IHI. The frequency was not significantly higher than in controls. There is no causality between temporal lobe epilepsy and IHI. 44% of the Rolandic epilepsy patients and 57% of the cryptogenic generalized epilepsy patients had IHI. IHI can be a sign of possible disturbed cerebral development in other parts of the brain.

    Cranial ultrasound examinations of 160 premature children were analyzed. The age at examination was 23-24 GW in 24 children, 25-28 GW in 72 children, and 29-36 GW in 64 children. IHI was found in 50%, 25% and 14%, respectively. The frequency difference between the children < 25 GW and > 25 GW was statistically significant (p< 0.001). From 25 GW onwards, the frequency and laterality of IHI is similar to that in the adult population.

    MRIs of 63 fetuses without intracranial pathology were reviewed independently by two radiologists. Three MRIs were performed post mortem at gestation week (GW) 17-18 and 60 in utero at GW 19-35. The hippocampal sulcus was open, bi- or unilaterally, in 35 fetuses at GW 17-32. The oldest of them was at GW 32.  The sulcus was closed at GW 21 at the earliest, unilaterally, and always from GW 33 onwards bilaterally. In 26/63 fetuses (41%), the hippocampal development was asymmetric and in 23 fetuses, the right side had developed faster.

    List of papers
    1. Incomplete inversion of the hippocampus: a common developmental anomaly
    Open this publication in new window or tab >>Incomplete inversion of the hippocampus: a common developmental anomaly
    Show others...
    2008 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 18, no 1, p. 138-142Article in journal (Refereed) Published
    Abstract [en]

    Incomplete inversion of the hippocampus, an imperfect fetal development, has been described in patients with epilepsy or severe midline malformations. We studied this condition in a nonepileptic population without obvious developmental anomalies. We analyzed the coronal MR images of 50 women and 50 men who did not have epilepsy. Twenty of them were healthy volunteers and 80 were patients without obvious intracranial developmental anomalies, intracranial masses, hydrocephalus or any condition affecting the temporal lobes. If the entire hippocampus (the head could not be evaluated) were affected, the incomplete inversion was classified as total, otherwise as partial. Incomplete inversion of the hippocampus was found in 19/100 subjects (9 women, 10 men). It was unilateral, always on the left side, in 13 subjects (4 women, 9 men): 9 were of the total type, 4 were partial. It was bilateral in six subjects (five women, one man): four subjects had total types bilaterally, two had a combination of total and partial types. The collateral sulcus was vertically oriented in all subjects with a deviating hippocampal shape. We conclude that incomplete inversion of the hippocampus is not an unusual morphologic variety in a nonepileptic population without other obvious intracranial developmental anomalies.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-15863 (URN)10.1007/s00330-007-0735-6 (DOI)000252593500016 ()17828540 (PubMedID)
    Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2017-12-08Bibliographically approved
    2. Incomplete hippocampal inversion-is there a relation to epilepsy?
    Open this publication in new window or tab >>Incomplete hippocampal inversion-is there a relation to epilepsy?
    Show others...
    2009 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 19, no 10, p. 2544-2550Article in journal (Refereed) Published
    Abstract [en]

    Incomplete hippocampal inversion (IHI) has been described in patients with epilepsy or severe midline malformations but also in nonepileptic subjects without obvious developmental anomalies. We studied the frequency of IHI in different epilepsy syndromes to evaluate their relationship. Three hundred patients were drawn from the regional epilepsy register. Of these, 99 were excluded because of a disease or condition affecting the temporal lobes or incomplete data. Controls were 150 subjects without epilepsy or obvious intracranial developmental anomalies. The coronal MR images were analysed without knowledge of the clinical data. Among epilepsy patients, 30% had IHI (40 left-sided, 4 right-sided, 16 bilateral). Of controls, 18% had IHI (20 left-sided, 8 bilateral). The difference was statistically significant (P < 0.05). Of temporal lobe epilepsy (TLE) patients, 25% had IHI, which was not a significantly higher frequency than in controls (P = 0.34). There was no correlation between EEG and IHI laterality. A total of 44% of Rolandic epilepsy patients and 57% of cryptogenic generalised epilepsy patients had IHI. The IHI frequency was very high in some epileptic syndromes, but not significantly higher in TLE compared to controls. No causality between TLE and IHI could be found. IHI can be a sign of disturbed cerebral development affecting other parts of the brain, maybe leading to epilepsy.

    Keywords
    Hippocampus, Developmental brain anomalies, MRI, Epilepsy
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-105372 (URN)10.1007/s00330-009-1438-y (DOI)000270268700029 ()19440714 (PubMedID)
    Available from: 2009-06-03 Created: 2009-06-03 Last updated: 2017-12-13Bibliographically approved
    3. Hippocampal development at gestation weeks 23 to 36: An ultrasound study on preterm neonates
    Open this publication in new window or tab >>Hippocampal development at gestation weeks 23 to 36: An ultrasound study on preterm neonates
    2010 (English)In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 52, no 6, p. 489-494Article in journal (Refereed) Published
    Abstract [en]

    INTRODUCTION: During fetal development, the hippocampal structures fold around the hippocampal sulcus into the temporal lobe. According to the literature, this inversion should be completed at gestation week (GW) 21. Thereafter, the hippocampal shape should resemble the adult shape. However, incomplete hippocampal inversion (IHI) is found in 19% of the common population. The aim of this study was to study fetal hippocampal development by examining neonates born preterm. METHODS: We analyzed cranial ultrasound examinations, performed as a part of the routine assessment of all preterm infants, over a 3-year period and excluded the infants with brain pathology. The final material consisted of 158 children born <35 GW. A rounded form (the ratio between the horizontal and vertical diameters of the hippocampal body <25 GW and >/=25 GW was statistically highly significant (p < 0.001). The frequency of bilateral IHI was highest in the youngest age group. In the other groups, the left-sided IHI was the most common. CONCLUSION: In about 50% of the neonates, hippocampal inversion is not completed up to GW 24; but from 25 GW onwards, the frequency and laterality of IHI is similar to that in the adult population.

    Keywords
    Fetal development, Ultrasonography, Hippocampus, Premature infants, Gestational age, Malrotation
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-124857 (URN)10.1007/s00234-010-0673-x (DOI)000277790000003 ()20352419 (PubMedID)
    Available from: 2010-05-06 Created: 2010-05-06 Last updated: 2017-12-12Bibliographically approved
    4. Asymmetric Development of the Hippocampal Region Is Common: A Fetal MR Imaging Study
    Open this publication in new window or tab >>Asymmetric Development of the Hippocampal Region Is Common: A Fetal MR Imaging Study
    2012 (English)In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 33, no 3, p. 513-518Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND AND PURPOSE: Hippocampal development is poorly understood. This study evaluated the normal development of the hippocampal region during the fetal period by using MR imaging.

    MATERIALS AND METHODS: MR images of 63 fetuses without intracranial pathology were reviewed independently by 2 radiologists with no knowledge of the fetal GA. Three MR images were performed postmortem and 60 in vivo. The progress of hippocampal inversion was analyzed in coronal sections, and the left and right sides of the hippocampal region were compared in every case.

    RESULTS: The fetuses in the postmortem examinations were at GWs 17-18 and in the in vivo examinations, at GWs 19-36. The hippocampal sulcus was open, bi- or unilaterally, in 39 fetuses. The oldest was at GW 32. The sulcus was closed at GW 21 at the earliest, unilaterally. In 26/63 fetuses (41%), the deepening or closure of the hippocampal sulcus or hippocampal inversion was asymmetric; in 23 fetuses, the right side developed faster. A shallow collateral sulcus was found earliest at GW 17. A deep collateral sulcus was visible earliest at GW 26 unilaterally, but in all fetuses from GW 31 onward, it was seen bilaterally. The orientation of the collateral sulcus was not related to the GA.

    CONCLUSIONS: There are wide individual temporal variations in the development and the inversion process of the hippocampal sulcus as well as in the formation of the collateral sulcus. Asymmetric development is common, and in most of the asymmetric cases, the right hippocampus develops faster.

    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Research subject
    Radiology
    Identifiers
    urn:nbn:se:uu:diva-131994 (URN)10.3174/ajnr.A2814 (DOI)000301870300024 ()
    Available from: 2010-10-12 Created: 2010-10-12 Last updated: 2017-12-12Bibliographically approved
  • 13.
    Bajic, Dragan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Canto Moreira, Nuno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Asymmetric Development of the Hippocampal Region Is Common: A Fetal MR Imaging Study2012In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 33, no 3, p. 513-518Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Hippocampal development is poorly understood. This study evaluated the normal development of the hippocampal region during the fetal period by using MR imaging.

    MATERIALS AND METHODS: MR images of 63 fetuses without intracranial pathology were reviewed independently by 2 radiologists with no knowledge of the fetal GA. Three MR images were performed postmortem and 60 in vivo. The progress of hippocampal inversion was analyzed in coronal sections, and the left and right sides of the hippocampal region were compared in every case.

    RESULTS: The fetuses in the postmortem examinations were at GWs 17-18 and in the in vivo examinations, at GWs 19-36. The hippocampal sulcus was open, bi- or unilaterally, in 39 fetuses. The oldest was at GW 32. The sulcus was closed at GW 21 at the earliest, unilaterally. In 26/63 fetuses (41%), the deepening or closure of the hippocampal sulcus or hippocampal inversion was asymmetric; in 23 fetuses, the right side developed faster. A shallow collateral sulcus was found earliest at GW 17. A deep collateral sulcus was visible earliest at GW 26 unilaterally, but in all fetuses from GW 31 onward, it was seen bilaterally. The orientation of the collateral sulcus was not related to the GA.

    CONCLUSIONS: There are wide individual temporal variations in the development and the inversion process of the hippocampal sulcus as well as in the formation of the collateral sulcus. Asymmetric development is common, and in most of the asymmetric cases, the right hippocampus develops faster.

  • 14.
    Bajic, Dragan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Hippocampal development at gestation weeks 23 to 36: An ultrasound study on preterm neonates2010In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 52, no 6, p. 489-494Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: During fetal development, the hippocampal structures fold around the hippocampal sulcus into the temporal lobe. According to the literature, this inversion should be completed at gestation week (GW) 21. Thereafter, the hippocampal shape should resemble the adult shape. However, incomplete hippocampal inversion (IHI) is found in 19% of the common population. The aim of this study was to study fetal hippocampal development by examining neonates born preterm. METHODS: We analyzed cranial ultrasound examinations, performed as a part of the routine assessment of all preterm infants, over a 3-year period and excluded the infants with brain pathology. The final material consisted of 158 children born <35 GW. A rounded form (the ratio between the horizontal and vertical diameters of the hippocampal body <25 GW and >/=25 GW was statistically highly significant (p < 0.001). The frequency of bilateral IHI was highest in the youngest age group. In the other groups, the left-sided IHI was the most common. CONCLUSION: In about 50% of the neonates, hippocampal inversion is not completed up to GW 24; but from 25 GW onwards, the frequency and laterality of IHI is similar to that in the adult population.

  • 15.
    Bajic, Dragan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Kumlien, Eva
    Mattsson, P.
    Lundberg, S.
    Eeg-Olofsson, Orvar
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Relationship of incomplete hippocampal inversion and epilepsy2008In: The XXXIII Congress of the European Society of Neuroradiology, Krakow, Poland, Springer , 2008, p. S45-Conference paper (Refereed)
  • 16.
    Bajic, Dragan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Kumlien, Eva
    Mattsson, P.
    Lundberg, S.
    Wang, C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Eeg-Olofsson, Orvar
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Incomplete inversions of the hippocampus in subjects without severe developmental anomalies. Is there a relationship to epilepsy?: European Congress of Radiology (ECR), Vienna, Austria2008In: Book of abstracts / ECR 2008, Berlin: Springer , 2008, p. 327-Conference paper (Refereed)
  • 17.
    Bajic, Dragan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Mattsson, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Lundberg, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wang, Chen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Incomplete hippocampal inversion-is there a relation to epilepsy?2009In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 19, no 10, p. 2544-2550Article in journal (Refereed)
    Abstract [en]

    Incomplete hippocampal inversion (IHI) has been described in patients with epilepsy or severe midline malformations but also in nonepileptic subjects without obvious developmental anomalies. We studied the frequency of IHI in different epilepsy syndromes to evaluate their relationship. Three hundred patients were drawn from the regional epilepsy register. Of these, 99 were excluded because of a disease or condition affecting the temporal lobes or incomplete data. Controls were 150 subjects without epilepsy or obvious intracranial developmental anomalies. The coronal MR images were analysed without knowledge of the clinical data. Among epilepsy patients, 30% had IHI (40 left-sided, 4 right-sided, 16 bilateral). Of controls, 18% had IHI (20 left-sided, 8 bilateral). The difference was statistically significant (P < 0.05). Of temporal lobe epilepsy (TLE) patients, 25% had IHI, which was not a significantly higher frequency than in controls (P = 0.34). There was no correlation between EEG and IHI laterality. A total of 44% of Rolandic epilepsy patients and 57% of cryptogenic generalised epilepsy patients had IHI. The IHI frequency was very high in some epileptic syndromes, but not significantly higher in TLE compared to controls. No causality between TLE and IHI could be found. IHI can be a sign of disturbed cerebral development affecting other parts of the brain, maybe leading to epilepsy.

  • 18.
    Bajic, Dragan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Wang, Chen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Mattsson, P.
    Lundberg, Staffan
    Eeg-Olofsson, Orvar
    Kumlien, E.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Incomplete inversion of the hippocampus: A common developmental anomaly.: European Congress of Radiology, Vienna, Austria.2007Conference paper (Refereed)
  • 19.
    Bajic, Dragan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Wang, Cheng
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Mattsson, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Lundberg, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Eeg-Olofsson, Orvar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Incomplete inversion of the hippocampus: a common developmental anomaly2008In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 18, no 1, p. 138-142Article in journal (Refereed)
    Abstract [en]

    Incomplete inversion of the hippocampus, an imperfect fetal development, has been described in patients with epilepsy or severe midline malformations. We studied this condition in a nonepileptic population without obvious developmental anomalies. We analyzed the coronal MR images of 50 women and 50 men who did not have epilepsy. Twenty of them were healthy volunteers and 80 were patients without obvious intracranial developmental anomalies, intracranial masses, hydrocephalus or any condition affecting the temporal lobes. If the entire hippocampus (the head could not be evaluated) were affected, the incomplete inversion was classified as total, otherwise as partial. Incomplete inversion of the hippocampus was found in 19/100 subjects (9 women, 10 men). It was unilateral, always on the left side, in 13 subjects (4 women, 9 men): 9 were of the total type, 4 were partial. It was bilateral in six subjects (five women, one man): four subjects had total types bilaterally, two had a combination of total and partial types. The collateral sulcus was vertically oriented in all subjects with a deviating hippocampal shape. We conclude that incomplete inversion of the hippocampus is not an unusual morphologic variety in a nonepileptic population without other obvious intracranial developmental anomalies.

  • 20.
    Bannbers, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kask, Kristiina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lower levels of prepulse inhibition in luteal phase cycling women in comparison with postmenopausal women2010In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 35, no 3, p. 422-429Article in journal (Refereed)
    Abstract [en]

    Menopause denotes the end of the reproductive period in a woman's life and is characterized by gradually declining plasma levels of ovarian hormones. Mounting evidence suggests that prepulse inhibition (PPI) is sensitive to fluctuations in estradiol and progesterone. Deficits in PPI are associated with conditions characterized by increased levels of ovarian steroids, such as the mid-luteal phase of the menstrual cycle and the third trimester of pregnancy. The aim of the current study was to further elucidate ovarian steroid-related effects on PPI by examining 43 women with regular menstrual cycles, 20 healthy postmenopausal women without hormone replacement treatment (HRT) and 21 healthy postmenopausal women with ongoing estradiol-only or estradiol and progesterone therapy (EPT). Cycling women were tested during the late luteal phase of the menstrual cycle while postmenopausal women were tested on any arbitrary day. The PPI was measured by electromyography. Cycling women exhibited lower levels of PPI than postmenopausal women (p<0.05). There were no differences in PPI between postmenopausal HRT users and non-users. However, postmenopausal women with estradiol serum concentrations in the cycling range had lower PPI than postmenopausal women with low estradiol concentrations (groupxPPI interaction, p<0.05). In conclusion, the results further suggest a role for the ovarian steroids in PPI regulation as PPI is increased in postmenopausal women in comparison to regularly menstruating women examined during the late luteal phase. Furthermore, postmenopausal women with estradiol levels in the cycling range had lower PPI than postmenopausal women with low estradiol levels.

  • 21. Baranto, Adad
    et al.
    Hellström, Mikael
    Cederlund, C-G.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Swärd, Leif
    Back pain and MRI changes in the thoraco-lumbar spine of top athletes in four different sports: a 15-year follow-up study2009In: Knee Surgery, Sports Traumatology, Arthroscopy, ISSN 0942-2056, E-ISSN 1433-7347, Vol. 17, no 9, p. 1125-1134Article in journal (Refereed)
    Abstract [en]

    A total 71 male athletes (weight lifters, wrestlers, orienteers, and ice-hockey players) and 21 non-athletes were randomly selected, for a baseline MRI study. After 15 years all the participants at baseline were invited to take part in a follow-up examination, including a questionnaire on back pain and a follow-up MRI examination. Thirty-two athletes and all non-athletes had disc height reduction at one or several disc levels. Disc degeneration was found in more than 90% of the athletes and deterioration had occurred in 88% of the athletes, with the highest frequency in weight lifters and ice-hockey players. 78% of the athletes and 38% of the non-athletes reported previous or present history of back pain at baseline and 71 and 75%, respectively at follow-up. There was no statistically significant correlation between back pain and MRI changes. In conclusion, athletes in sports with severe or moderate demands on the back run a high risk of developing disc degeneration and other abnormalities of the spine on MRI and they report high frequency of back pain. The study confirmed our hypothesis, i.e. that most of the spinal abnormalities in athletes seem to occur during the growth spurt, since the majority of the abnormalities demonstrated at follow-up MRI after the sports career were present already at baseline. The abnormalities found at young age deteriorated to a varying degree during the 15-year follow-up, probably due to a combination of continued high load sporting activities and normal ageing. Preventive measures should be considered to avoid the development of these injuries in young athletes.

  • 22. Baranto, Adad
    et al.
    Hellström, Mikael
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Lundin, Olof
    Swärd, Leif
    Back pain and degenerative abnormalities in the spine of young elite divers: a 5-year follow-up magnetic resonance imaging study2006In: Knee Surgery, Sports Traumatology, Arthroscopy, ISSN 0942-2056, E-ISSN 1433-7347, Vol. 14, no 9, p. 907-914Article in journal (Refereed)
    Abstract [en]

    Several studies have been published on disc degeneration among young athletes in sports with great demands on the back, but few on competitive divers; however, there are no long-term follow-up studies. Twenty elite divers between 10 and 21 years of age, with the highest possible national ranking, were selected at random without knowledge of previous or present back injuries or symptoms for an MRI study of the thoraco-lumbar spine in a 5-year longitudinal study. The occurrence of MRI abnormalities and their correlation with back pain were evaluated. Eighty-nine percent of the divers had a history of back pain and the median age at the first episode of back pain was 15 years. Sixty-five percent of the divers had MRI abnormalities in the thoraco-lumbar spine already at baseline. Only one diver without abnormalities at baseline had developed abnormalities at follow-up. Deterioration of any type of abnormality was found in 9 of 17 (53%) divers. Including all disc levels in all divers, the total number of abnormalities increased by 29% at follow-up, as compared to baseline. The most common abnormalities were reduced disc signal, Schmorl's nodes, and disc height reduction. Since almost all divers had previous or present back pain, a differentiated analysis of the relationship between pain and MRI findings was not possible. However, the high frequency of both back pain and MRI changes suggests a causal relationship. In conclusion, elite divers had high frequency of back pain at young ages and they run a high risk of developing degenerative abnormalities of the thoraco-lumbar spine, probably due to injuries to the spine during the growth spurt.

  • 23.
    Berglund, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Three-point Dixon method enables whole-body water and fat imaging of obese subjects2010In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 63, no 6, p. 1659-1668Article in journal (Refereed)
    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.

  • 24.
    Bergqvist, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Holst, Jan
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Skiöldebrand, Claes
    Takolander, Rabbe
    Svårkontrollerad blödning vid kirurgi - praktiska åtgärder2007In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, no 6, p. 407-411Article in journal (Refereed)
    Abstract [en]

    Difficult-to-control intraoperative bleeding--practical measures

    Bleeding with difficulties obtaining haemostasis can be a catastrophe. This paper summarizes a symposium with the above title. A short introduction gives the background of normal haemostasis as well as iatrogenic vascular injuries as reflected in the Swedish vascular registry (Swedvasc). Practical guidelines are given on how to manage situations of severe haemorrhage with the help of pharmacological substances, local haemostatics, endovascular methodology and open surgery.

  • 25.
    Bergqvist, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ljungman, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Treatment options for abdominal aortic aneurysm (AAA)2006In: Vascular Surgery / [ed] Alun H. Davies, London: Springer , 2006Chapter in book (Other academic)
  • 26.
    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.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Secondary aortoenteric fistula after endovascular aortic interventions: a systematic literature review2008In: Journal of Vascular and Interventional Radiology, ISSN 1051-0443, E-ISSN 1535-7732, Vol. 19, no 2, p. 163-165Article, review/survey (Refereed)
    Abstract [en]

    PURPOSE: To evaluate the collective incidence of, and experience with, aortoenteric fistula after endovascular aortoiliac therapy. MATERIALS AND METHODS: A systematic literature research was performed to identify cases of aortoenteric fistulation after aortic stent-graft procedures or stent implantation. RESULTS: The review revealed 16 cases of aortoenteric fistulation after aortic stent-grafting (n = 15) or stent placement (n = 1), in 14 patients with abdominal aortic aneurysm. Six had undergone endovascular aneurysm repair because of what was considered a "hostile abdomen." The symptoms did not differ from those in patients with arterioenteric fistulation after open aortic repair. A defect in the stent-graft or its function was the predominant cause of fistulation. One fistula was diagnosed at autopsy, two patients died perioperatively, and 13 survived with in situ repair or an axillobifemoral graft, all after removal of the stent-graft or stent. However, the follow-up time was short, longer than 1 year in only five of the 13 survivors. CONCLUSIONS: Aortoenteric fistulation does occur after endovascular implantation of stents and stent-grafts. The incidence is unknown but is probably low. Follow-up time in most publications was less than 1 year, which is considered short to assess potential graft infection.

  • 27.
    Björkman, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Eklöf, Hampus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Wadström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Andersson, L-G.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Split renal function in patients with suspected renal artery stenosis: a comparison between gamma camera renography and two methods of measurements with computed tomography2006In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 47, no 1, p. 107-113Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To validate a method for calculating split renal function from computed tomography (CT) compared with gamma camera renography, and to test a new method for the measurement based on a volume-rendering technique. MATERIAL AND METHODS: Thirty-eight patients, aged 65.7 +/- 11.6 (range 37.8-82.1) years, who had undergone both CT angiography and gamma camera renography for a suspected renal artery stenosis were included in this study. Split renal function was calculated from the CT examinations by measuring area and mean attenuation in the image slices of the kidneys, and also by measuring volume and mean attenuation from a 3D reconstruction of the kidneys. Gamma camera renography with 99mTc-MAG3 with or without captopril enhancement was used as a reference. RESULTS: The 2D CT method had good correlation with renography (r=0.93). Mean difference was 4.7 +/- 3.6 (0-12) percentage points per kidney. There was also excellent correlation between the two CT methods (r=1.00). CONCLUSION: CT is equivalent to renography in determining split renal function, and the measurement from the CT examination can be made more quickly and equally accurately with a 3D technique.

  • 28.
    Bojler, Therese
    et al.
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Business Studies.
    Björlin, Jeanette
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Business Studies.
    Entering the Swedish Management Consulting Industry: A qualitative study of what factors to consider when entering the Swedish management consulting industry2008Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The management consultancy, a 14 billion EUR industry in Europe, has become an attractive market in the last couple of years. The Swedish market is blooming with an economic growth of a staggering 20 % according to analysts at Konsultguiden. The attractiveness of the market has brought many foreign players into the field such as Celerant. Celerant is a UK-based company earning a total of $145 million in 2006 with about 650 employees around Europe and the USA. Their focus is mainly within operational management. A few years ago, Celerant decided to expand in to the Nordic region consisting of Denmark, Norway and Sweden and has just recently started to focus a bit extra on the Swedish market. Using Porter’s model of Five Forces we look at the Swedish management consulting industry to see what factors to consider focusing on when entering the market. Through an analysis of the current management consulting market, we compare it to Celerant’s strategy for entering the Swedish market to see if our analysis differs or is similar to the consultancy’s actual strategy. This gives us a picture of how the management consultancies perceive the market and how they act accordingly. The results show similarities with two factors: the consultants and the clients. These seem to be the main factors to focus on as a management consultancy entering the Swedish market. There seems to be a current shortage of competent consultants on the Swedish market and therefore a necessity to focus on recruitment. Clients are what make business for consultancies and business connections need to be established before entering the market. However, we found that more precaution should be taken for factors such as substitutes and new entrants as well. There is a constant change of trends in the management consultancy industry and needs to be considered in order to stay competitive on the market, since a management consultancy needs to be able to offer what the clients demand.

  • 29.
    Briley-Saebo, Karen C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Johansson, Lars O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Hustvedt, Svein Olaf
    Haldorsen, Anita G.
    Bjornerud, Atle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Fayad, Zahi A.
    Ahlström, Håkan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Clearance of iron oxide particles in rat liver: effect of hydrated particle size and coating material on liver metabolism2006In: Investigative Radiology, ISSN 0020-9996, E-ISSN 1536-0210, Vol. 41, no 7, p. 560-571Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: We sought to evaluate the effect of the particle size and coating material of various iron oxide preparations on the rate of rat liver clearance. MATERIALS AND METHODS: The following iron oxide formulations were used in this study: dextran-coated ferumoxide (size = 97 nm) and ferumoxtran-10 (size = 21 nm), carboxydextran-coated SHU555A (size = 69 nm) and fractionated SHU555A (size = 12 nm), and oxidized-starch coated materials either unformulated NC100150 (size = 15 nm) or formulated NC100150 injection (size = 12 nm). All formulations were administered to 165 rats at 2 dose levels. Quantitative liver R2* values were obtained during a 63-day time period. The concentration of iron oxide particles in the liver was determined by relaxometry, and these values were used to calculate the particle half-lives in the liver. RESULTS: After the administration of a high dose of iron oxide, the half-life of iron oxide particles in rat liver was 8 days for dextran-coated materials, 10 days for carboxydextran materials, 14 days for unformulated oxidized-starch, and 29 days for formulated oxidized-starch. CONCLUSIONS: The results of the study indicate that materials with similar coating but different sizes exhibited similar rates of liver clearance. It was, therefore, concluded that the coating material significantly influences the rate of iron oxide clearance in rat liver.

  • 30. Burman, Pia
    et al.
    Lethagen, ÅsaLinda
    Ivancev, Krasnodar
    Johansson, Leif
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Dual bronchial carcinoids and Cushing's syndrome with a paradoxical response to dexamethasone and a false positive outcome of inferior petrosal sinus sampling2008In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 159, no 4, p. 483-8Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Establishing the cause of Cushing's syndrome (CS) can be a considerable challenge, in particular in ectopic adrenocorticotropic hormone (ACTH) syndrome, and often requires a combination of biochemical tests and imaging procedures. SUBJECT: A 27-year-old man presented with signs of CS. P-ACTH levels were three times above the upper limit of normal (ULN) and free urinary cortisol around 2000 nmol/24 h. The work-up showed remarkable results. RESULTS: A 2-day low-dose dexamethasone suppression test demonstrated paradoxical increases in cortisol. Sampling from the bilateral inferior petrosal sinus sampling (BIPSS) showed a central to peripheral ACTH ratio of 4.7 after corticotrophin-releasing hormone (CRH) stimulation, i.e. indicated pituitary disease, but magnetic resonance imaging of the pituitary was normal. Computed tomography (CT) scan of the lungs showed two oval-shaped masses, 1.3 x 1.8 and 1.3 x 2 cm, in the middle lobe. Both were positive at somatostatin receptor scintigraphy, compatible with tumors or inflammatory lesions. Subsequently, (11)C-5-hydroxytryptophan-PET showed distinct uptake in the tumors but not elsewhere. Two carcinoids situated 3 cm apart, both staining for ACTH, were removed at surgery. CONCLUSION: This unique case with dual bronchial carcinoids inducing hypercortisolism illustrates the problems with identifying the source of ACTH in CS. Possibly, an abnormal regulation of ACTH production in response to dexamethasone, or steroid-induced tumor necrosis, explains the paradoxical outcome at dexamethasone suppression, and the false positive result at BIPSS reflects an unusual sensitivity of the pituitary corticotrophs to CRH in this patient. The work-up illustrates the great value of (11)C-5-hydroxytryptophan-PET as a diagnostic procedure when other investigations have produced ambiguous results.

  • 31.
    Carlsson, Jörgen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Liljegren, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Sjöström, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Westlin, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Zhao, Qinghai
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Conjugate chemistry and cellular processing of EGF-dextran1999In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 38, no 3, p. 313-321Article in journal (Refereed)
    Abstract [en]

    Conjugates with specific binding to the epidermal growth factor receptor, EGFR, of interest for radionuclide based imaging and therapy were prepared using mouse epidermal growth factor, mEGF, and dextran. In one type of conjugate, mEGF was coupled to dextran by reductive amination in which the free amino group on the mEGF N-terminal reacted with the aldehyde group on the reductive end of dextran. The end-end coupled conjugate could be further activated by the cyanopyridinium agent CDAP, thereby introducing tyrosines to the dextran part. In the other type of conjugate, the cyanylating procedure using CDAP was applied, first to activate dextran and then allowing for the amino terminus of mEGF to randomly attach to the dextran. In the latter case, radionuclide-labelled tyrosines or glycines could be added in the same conjugation step. All types of mEGF-dextran conjugates had EGFR-specific binding since the binding could be displaced by an excess of non-radioactive mEGF. The conjugates were to a large extent internalized in the test cells and the associated radioactivity was retained intracellularly for different times depending on both the type of cells and conjugate applied. Different intracellular 'traffic routes' for the radionuclides are discussed as well as applications for both imaging and therapy.

  • 32.
    Christoffersson, Gustaf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Henriksnäs, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Rolny, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Caballero-Corbalán, José
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Segersvärd, Ralf
    Permert, Johan
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Phillipson, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Clinical and Experimental Pancreatic Islet Transplantation to Striated Muscle: Establishment of a Vascular System Similar to that in Native Islets2010In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 59, no 10, p. 2569-2578Article in journal (Refereed)
    Abstract [en]

    Objective: Curing type 1 diabetes by transplanting pancreatic islets into the liver is associated with poor long-term outcome and graft failure at least partly due to inadequate graft revascularization. The aim of the current study was to evaluate striated muscle as a potential angiogenic site for islet transplantation. Research Design and Methods: The current study presents a new experimental model which is found applicable to clinical islet transplantation. Islets were implanted into striated muscle where after intra-islet vascular density and blood flow were visualized with intravital and confocal microscopy in mice, and by magnetic resonance imaging in three auto-transplanted pancreatectomized patients. Mice were rendered neutropenic by repeated injections of Gr-1 antibody and diabetes was induced by alloxan treatment. Results: Contrary to liver-engrafted islets, islets transplanted to mouse muscle were revascularized with vessel densities and blood flow entirely comparable to islets within intact pancreas. Initiation of islet revascularization at the muscular site was dependent on neutrophils, and the function of islets transplanted to muscle was proven by curing diabetic mice. The experimental data were confirmed in auto-transplanted patients where higher plasma volumes were measured in islets engrafted in forearm muscle compared to adjacent muscle tissue through high-resolution magnetic resonance imaging. Conclusions: This study presents a novel paradigm in islet transplantation whereby recruited neutrophils are crucial for the functionally restored intra-islet blood perfusion following transplantation to striated muscle under experimental and clinical situations.

  • 33.
    Cornefjord, Michael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Henriques, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Alemany, Montserrat
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Olerud, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Posterior atlanto-axial fusion with the Olerud cervical fixation system for odontoid fractures and C1-C2 instability in reumathoid arthritis2003In: European spine journal, ISSN 0940-6719, E-ISSN 1432-0932, Vol. 12, no 1, p. 91-96Article in journal (Refereed)
    Abstract [en]

    In posterior C1-C2 fusion, traditional wire fixation gives poor stability. The bone quality is often insufficient to provide the competent structural bone graft that is required, and the introduction of sublaminar wires is somewhat dangerous. The stability is markedly improved by adding transarticular screws, but the drawbacks of structural bone graft and sublaminar wires remain. The C1 claw of the Olerud Cervical Fixation System improves C1-C2 fixation without relying on structural bone graft or compromising the spinal canal. The aim of this study was to evaluate radiological healing and possible complications in a consecutive series of C1-C2 fusions from our department operated with the C1 claw device. Twenty-six patients (14 women) with a mean age of 73 (range 37-93) years were included. The diagnoses were odontoid fracture in 18 patients, rheumatoid instability in 6, and odontoid non-union and os odontoideum in 1 each. The patients were followed clinically and with plain radiographs for an average of 15 (range 3-27) months. There were no neurological or vascular complications, and no secondary displacements or reoperations in the series. Twenty patients followed for 6-27 months were radiographically healed. Six patients died from unrelated causes 1-38 months postoperatively. Three of these patients had no radiographs later than the postoperative control, one had a healed odontoid fracture but resorbed bone graft at 8 months, while the remaining two patients were not healed, but showed no signs of healing disturbance at the time of death. On the basis of the findings of this study, posterior C1-C2 fusion with the Olerud Cervical Fixation System seems promising. No serious complications related to the surgical procedure were encountered. The stability of the implant obviates the use of a solid bone block as a graft and still allows a high frequency of fusion healing.

  • 34.
    Covaciu, Lucian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Ortiz-Nieto, Francisco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Human brain MR spectroscopy thermometry using metabolite aqueous-solution calibrations2010In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 31, no 4, p. 807-814Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To estimate absolute brain temperature using proton MR spectroscopy ((1)H-MRS) and mean brain-body temperature difference of healthy human volunteers. MATERIALS AND METHODS: Chemical shift difference between temperature-dependent water spectral line position and temperature-stable metabolite spectral reference was used for the estimations of absolute brain temperature. Temperature calibrations constants were obtained from the spectra of the N-acetyl aspartate (NAA line at approximately 2.0 ppm), glycero-phosphocholine (GPC line at approximately 3.2 ppm), and creatine (Cr line at approximately 3.0 ppm) aqueous solutions with pH values within physiologically pertinent ranges. Single-voxel PRESS sequence (TR/TE 2000/80 ms) was used for this purpose. Brain temperature was determined by averaging the temperatures computed from water-Cho, water-Cr, and water-NAA chemical shift differences. RESULTS: The mean brain temperature of 18 healthy volunteers was 38.1 +/- 0.4 degrees C and mean brain-body (rectal) temperature difference was 1.3 +/- 0.4 degrees C. CONCLUSION: Improved accuracy of the temperature constants and averaging the temperatures computed from water-Cho, water-Cr, and water-NAA chemical shift differences increased the reliability of the brain temperature estimations.

  • 35.
    Covaciu, Lucian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Bengtsson, Caroline
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Allers, Mats
    Division of thoracic sciences, Department of clinical sciences, Lund University.
    Lunderquist, Anders
    Department of radiology, Lund University.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Brain temperature in healthy volunteers subjected to intranasal cooling2011In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 37, no 8, p. 1277-1284Article in journal (Other academic)
    Abstract [en]

    Purpose:

    Intranasal cooling can be used to initiate therapeutic hypothermia. However, direct measurement of brain temperature is difficult and the intra-cerebral distribution of temperature changes with cooling is unknown. The purpose of this study was to measure the brain temperature of human volunteers subjected to intranasal cooling using non-invasive magnetic resonance (MR) methods.

    Methods:

    Intranasal balloons catheters circulated with saline at 20 °C were applied for 60 min in 10 healthy, unsedated volunteers. Brain temperature changes were measured and mapped using MR spectroscopic imaging (MRSI) and phase-mapping techniques. Heart rate and blood pressure were monitored throughout the experiment. Rectal temperature was measured before and after the cooling. Mini Mental State Examination (MMSE) test and nasal inspection were done before and after the cooling. Questionnaires about the subjects personal experience were filled after the experiment.

    Results:

    Brain temperature decrease measured by MRSI was -1.7 ± 0.8°C and by phase-mapping -1.8 ± 0.9°C at the end of cooling. Spatial distribution of temperature changes was relatively uniform. Rectal temperature decreased by -0.5 ± 0.3°C. The physiological parameters were stable and no shivering was reported. The volunteers remained alert during cooling and no cognitive dysfunctions were apparent at MMSE test. Postcooling nasal examination detected increased nasal secretion in 9 of the 10 volunteers. Volunteer’s acceptance of the method was good.   

    Conclusion:

    Both MR techniques revealed brain temperature reductions after 60 min intranasal cooling with balloons circulated with saline at 20 °C in healthy and unsedated volunteers.