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  • 151. Besselaar van den, AMHP
    et al.
    Houbouyan-Refeillard, LL
    Aillaud, MF
    Denson, KWE
    Johnston, M
    Kitchen, S
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Multicenter evaluation of lyophilized and deep-frozen plasmas for assignment of the international normalized ratio.1999In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 82, p. 1451-1455Article in journal (Refereed)
  • 152.
    Bivall Persson, Petter
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Science and Technology. Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA).
    Cooper, Matthew
    Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA). Linköping University, The Institute of Technology.
    Tibell, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Visuella och haptiska modeller för underlättad förståelse för molekylers struktur och interaktioner2007In: 10:e Universitetspedagogiska konferensen vid Linköpings universitet: Pedagogiska utmaningar i tiden / [ed] Helene Hård af Segerstad, 2007, p. 43-47Conference paper (Refereed)
  • 153.
    Bivall Persson, Petter
    et al.
    Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA). Linköping University, The Institute of Technology.
    Cooper, Matthew
    Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA). Linköping University, The Institute of Technology.
    Tibell, Lena
    Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Linköping University, Faculty of Health Sciences.
    Ainsworth, Shaaron
    Learning Sciences Research Institute, University of Nottingham, Nottingham, UK.
    Ynnerman, Anders
    Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA). Linköping University, The Institute of Technology.
    Jonsson, Bengt-Harald
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology. Linköping University, The Institute of Technology.
    Designing and Evaluating a Haptic System for Biomolecular Education2007In: IEEE Virtual Reality Conference, 2007. VR '07. / [ed] Sherman, W; Lin, M; Steed, A, Piscataway, NJ, USA: IEEE , 2007, p. 171-178Conference paper (Refereed)
    Abstract [en]

    In this paper we present an in situ evaluation of a haptic system, with a representative test population, we aim to determine what, if any, benefit haptics can have in a biomolecular education context. We have developed a haptic application for conveying concepts of molecular interactions, specifically in protein-ligand docking. Utilizing a semi-immersive environment with stereo graphics, users are able to manipulate the ligand and feel its interactions in the docking process. The evaluation used cognitive knowledge tests and interviews focused on learning gains. Compared with using time efficiency as the single quality measure this gives a better indication of a system's applicability in an educational environment. Surveys were used to gather opinions and suggestions for improvements. Students do gain from using the application in the learning process but the learning appears to be independent of the addition of haptic feedback. However the addition of force feedback did decrease time requirements and improved the students understanding of the docking process in terms of the forces involved, as is apparent from the students' descriptions of the experience. The students also indicated a number of features which could be improved in future development.

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  • 154.
    Bivall Persson, Petter
    et al.
    Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA). Linköping University, The Institute of Technology.
    Cooper, Matthew
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Ynnerman, Anders
    Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA). Linköping University, The Institute of Technology.
    Jonsson, Bengt-Harald
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology.
    Tibell, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Use of Chemical Force Feedback for Multisensory Insights into Ligand Docking2007In: VII European Symposium of The Protein Society: From Proteins to Proteome, 2007, p. 151-151Conference paper (Refereed)
  • 155.
    Bivall Persson, Petter
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Science and Technology. Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA).
    Tibell, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Cooper, Matthew
    Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA). Linköping University, The Institute of Technology.
    Using Force Feedback Virtual Reality Technology as a Tactile Gateway to Understanding of Biomolecular Interactions2006In: 9th JURE conference of EARLI, 2006Conference paper (Other academic)
  • 156.
    Bivall Persson, Petter
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Science and Technology. Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA).
    Tibell, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Cooper, Matthew D.
    Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA). Linköping University, The Institute of Technology.
    Ainsworth, Shaaron
    Learning Sciences Research Institute University of Nottingham.
    Reasoning through Touch? Using Haptics in Life Science Education2007In: EARLI 2007 12th Biennial Conference for Research on Learning and Instruction, 2007Conference paper (Other academic)
  • 157.
    Bivall Persson, Petter
    et al.
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Science & Engineering.
    Tibell, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Cooper, Matthew
    Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA). Linköping University, The Institute of Technology.
    Ynnerman, Anders
    Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA). Linköping University, The Institute of Technology.
    Jonsson, Bengt-Harald
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology.
    Evaluating the Effectiveness of Haptic Visualization in Biomolecular Education - Feeling Molecular Specificity in a Docking Task2006In: 12th IOSTE Symposium, Universiti Science Malaysia , 2006, p. 745-752Conference paper (Refereed)
    Abstract [en]

    Within the molecular life sciences extensive use is made of visual representations, ranging from sketches to advanced computer graphics, often used to convey abstract knowledge that is difficult for the student to grasp. This work evaluates a new visual and haptic (tactile/kinetic) tool for protein docking in an in situ learning situation by combining qualitative and quantitative methods, performing tests and interviews with students; all aiming at a proper inclusion of visualization tools into biomolecular education. Preliminary results indicate time gains, strong positive affective responses and learning gains from the tasks, however the influence of haptics needs further investigation.

  • 158. Bjellerup, P
    et al.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Jörnvall, H
    Kogner, P
    Limited neuropeptide Y precursor processing in unfavourable metastatic neuroblastoma tumours2000In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 83, no 2, p. 171-176Article in journal (Refereed)
    Abstract [en]

    Neuropeptide Y (NPY) is found at high concentrations in neural crest-derived tumours and has been implicated as a regulatory peptide in tumour growth and differentiation. Neuroblastomas, ganglioneuromas and phaeochromocytomas with significant concentrations of NPY-like immunoreactivity were investigated for different molecular forms of NPY and for significance of proNPY processing. Gel-permeation chromatography identified intact NPY (1-36) in all tumours, whereas proNPY (69 amino acids) was detected only in control adrenal tissue and malignant neuroblastomas. Purification of NPY-like immunoreactivity in tumour extracts and structural characterization revealed that both NPY (1-36) and the truncated form NPY (3-36) was present. The degree of processing of proNPY to NPY in tumour tissue was lower in advanced neuroblastomas with regional or metastatic spread (stage 3 and 4) (n = 6), (41%, 12-100%, median, range), compared to the less aggressive stage 1, 2 and 4S tumours (n = 12), (93%, 69-100%), (P = 0.012). ProNPY processing of less than 50% was correlated with poor clinical outcome (P = 0.004). MYCN oncogene amplification was also correlated to a low degree of proNPY processing (P = 0.025). In summary, a low degree of proNPY processing was correlated to clinical advanced stage and poor outcome in neuroblastomas. ProNPY/NPY processing generated molecular forms of NPY with known differences in NPY-receptor selectivity, implicating a potential for in vivo modulation of NPY-like effects in tumour tissue. (C) 2000 Cancer Research Campaign.

  • 159.
    Björk, Per
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry. Linköping University, The Institute of Technology.
    Lenner, Liselotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Persson, Birgitta
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Inganäs, Olle
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Jonasson, Jon
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Conjugated polythiophene probes target lysosome-related acidic vacuoles in cultured primary cells2007In: Molecular and Cellular Probes, ISSN 0890-8508, Vol. 21, no 5-6, p. 329-337Article in journal (Refereed)
    Abstract [en]

    Conformation-sensitive optical probes for studying biological processes and structures are of great interest. The present work shows for the first time that conjugated polyelectrolyte (CPE) probes can be used for specific targeting of chromatin, nuclear and cytoplasmatic vesicles, and cytoskeletal components in a complex system of cultured cells. One of the probes could also be used for vital staining of live cells. When bound to different entities, the polythiophene derivative probes emitted light with different colors due to the unique spectral properties of these conformation sensitive probes. The physical pre-requisites for binding could also be exploited for characterization of the target. Unexpectedly, lysosome-related acidic vacuoles were targeted in cultured primary cells by both anionic, cationic, and zwitter-ionic polythiophene derivatives. Pre-treatment with Bafilomycin A1, a specific inhibitor of vacuolar-type H+-ATPase, caused redistribution of the staining. The targeting of lysosome-related acidic vesicles could not be demonstrated in transformed cells (melanoma, neuroblastoma, and prostate cancer cell lines), indicating a difference in the localization, structure, accessibility, or quantity of the target in cultured normal cells as compared with the malignant cell lines. The chemical nature of the conjugated polyelectrolyte complex in the cytoplasmatic vacuoles remains elusive.

  • 160.
    Björnström, Karin
    et al.
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Holmgren, Susanna
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Loverock, A.
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Wijkman, Magnus
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Lindroth, Margareta
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Eintrei, Christina
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Rho and Rho Kinase are involved in the signal transduction cascade caused by propofolManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Propofol is known to interact with the γ-aminobutyric acidA (GABAA) receptor, however, activating the receptor alone is not sufficient for producing anaesthesia. Propofol tyresine phosphorylates the GABAA receptor and reorganises the actin cytoskeleton, eausing ring structures and rnembrane ruffles. Propofol, but not GABA, the endogenous tigand for the GABAA receptor, tyresine phosphorylates actin, both in the membrane and cytoskeletal fractions of the neuron.

    Aim: How does propofol cause the actin reorganisation and is this a specific effect of propofol? Is the small membrane associated G-protein rho involved in the signal cascade towards the actin reorganisation?

    Methods: Westem blotting (WB) was used to visualize tyresine phosphorylated immunoprecipitated proteins and changes in actin between the different cellularcompartments after inhibition with rho (C3 exotoxin) and rho kinase (ROK) (HA-1077) inhibitors. Fluoreseenee mireoscopy after rhodamine-phalloidin labelling of actin was used to calculate the number of actin ring structures caused by propofol or GABA, in same experiments combined with pre-incubation with C3 exotoxin, HA- 1077 or the tyrosine kinase inhibitor Herbimycin A. Propofol-stimulated cells were studied with confocal microscopy.

    Results: Propofol eaused an increased tyresine phosphorylation, that was reduced by C3 exotoxin, of a 160 kDa protein after two minutes stimulation. The 160 kDa protein is still unidentified. The actin ring structures caused by propofol was shown with confocal microscopy to go almost through the entire cell. The amount of rings were reduced by C3 exatoxin as well as HA-1077. Furthermore, w hen a tyrosine kinase bioeker was used no ring structures were formed. However, GABA did not produce any ring structures. When the actin content of the cellular campartments were analysed, C3 exatoxin treated cells showed an increased amount of actin in the cytoskeletal fraction, simultaneausly with a decrease in both the membrane and the cytosol fractions. The ROK bioeker on ly eaused a reduction of actin in the cytosol/membrane fractions, but no increase was observed in the cytoskeleton.

    Conclusion: Propofol, but not GABA, eauses actin ring structures in neurons. Propofol uses the rho and rho kinase pathway to reorganize the actin cytoskeleton into ring structures, which is also dependent on a tyresine klnase. Propofol also eauses an unidentified rho dependent 160 kDa protein to be tyresine phosphorylated. The activation eaused by propofol of rho and rho kinase causes actin to be moved from the cytoskeleton to the cell membrane and cytosol. This reorganisation of actin might influence the GABAA receptor by keeping it open, thus allowing the cell to be hyperpolarized for longer time, and consequently maintain anaesthesia.

  • 161.
    Björnström, Karin
    et al.
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Sjölander, Anita
    Division of Experimental Pathology, Lund University, Malmö, Sweden.
    Schippert, Åsa
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Eintrei, Christina
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    A tyrosine kinase regulates propofol-induced modulation of the β-subunit of the GABAA receptor and release of intracellular calcium in cortical rat neurones2002In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 175, no 3, p. 227-235Article in journal (Refereed)
    Abstract [en]

    Propofol, an intravenous anaesthetic, has been shown to interact with the β-subunit of the γ-amino butyric acidA (GABAA) receptor and also to cause changes in [Ca2+]i. The GABAA receptor, a suggested target for anaesthetics, is known to be regulated by kinases. We have investigated if tyrosine kinase is involved in the intracellular signal system used by propofol to cause anaesthesia. We used primary cell cultured neurones from newborn rats, pre-incubated with or without a tyrosine kinase inhibitor before propofol stimulation. The effect of propofol on tyrosine phosphorylation and changes in [Ca2+]i were investigated. Propofol (3 μg mL−1, 16.8 μM) increased intracellular calcium levels by 122 ± 34% (mean ± SEM) when applied to neurones in calcium free medium. This rise in [Ca2+]i was lowered by 68% when the cells were pre-incubated with the tyrosine kinase inhibitor herbimycin A before exposure to propofol (P < 0.05). Propofol caused an increase (33 ± 10%) in tyrosine phosphorylation, with maximum at 120 s, of the β-subunit of the GABAA-receptor. This tyrosine phosphorylation was decreased after pre-treatment with herbimycin A (44 ± 7%, P < 0.05), and was not affected by the absence of exogenous calcium in the medium. Tyrosine kinase participates in the propofol signalling system by inducing the release of calcium from intracellular stores and by modulating the β-subunit of the GABAA-receptor.

  • 162. Order onlineBuy this publication >>
    Blom, René
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Sarcoma of the female genital tract: Histopathology, DNA cytometry, p53 and mdm-2 analysis related to prognosis1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Sarcomas of the female genital tract are rare tumors and account for less than 5% of gynecologic malignancies. Traditionally, gynecologic sarcomas have been divided into different tumor types according to their histopathological features. The most common are leiomyosarcoma (LMS), malignant mixed Müllerian tumors (MMMT), endometrial stromal sarcoma (ESS) and (Müllerian) adenosarcoma. The different tumor types are highly aggressive with early lymphatic and/or hematogenous spread. Treatment is difficult and it is believed that sarcomas have a low radio-and chemosensitivity, and the mainstay in treatment is surgical removal of the tumor. The most important prognostic feature has been tumor stage. Nevertheless, there are some early-stage tumors that run a biological course different from that expected and additional prognostic factors indicating high-risk tumors are desirable.

    The study cohort consists of 49 uterine LMS, 44 uterine MMMTs, 17 uterine ESS, 11 uterine adenosarcomas and 26 ovarian MMMTs. The tumors were analyzed in a retrospective manner for DNA ploidy, S-phase fraction (SPF), p53 and mdm-2 expression, as well as traditional clinical and pathological prognostic factors, such as tumor stage. grade, atypia and mitotic index.

    Of the 49 LMS, 36 (86%) were non-diploid and 13 (27%) were p53-positive. Among the 44 uterine MMMTs, 30 (68%) were non-diploid and 27 (61%) had an SPF>10%. Twenty-seven (61%) overexpressed p53 and 11 (25%) were mdm-2 positive. Furthermore, 40 (91%) of the uterine MMMTs had a high mitotic count and 42 (95%) had high grade cytologic atypia. All low-grade ESS were DNA diploid and had a low SPF. Among the four high-grade ESS, three (75%) were DNA aneuploid and three (75%) were p53-positive. Among 1 1 adenosarcomas, eight (73%) were non-diploid. All ovarian MMMTs were non-diploid and all but two had an SPF>10%. 19 (73%) ovarian MMMTs were p53positive.

    The 5-year survival rate was 33% for LMS, 38% for uterine MMMT, 57% for ESS, 69% for adenosarcoma and 30% for ovarian MMMT.

    Thirty-five (71%) patients with LMS died of disease and two of intercurrent disease. Stage was found to be the most important factor for survival (p=0.007); in addition DNA ploidy (p=0.045) and SPF (p=0.041) had prognostic significance.

    Twenty-seven (61%) patients with uterine MMMT died of disease and six (14%) died of intercurrent disease. Stage was the only prognostic factor for survival.

    Nine (53%) patients with ESS died of disease. There was a significant correlation of survival to tumor grade (p=0.007), DNA ploidy (p=0.026), SPF (p=0.048) and stage (p=0.026).

    Of the 11 patients with adenosarcoma, four (36%) patients died of disease and three (27%) patients died of intercurrent disease. There were no variables that correlated with survival.

    Eighteen (69%) patients with ovarian MMMT died of disease and two (8%) patients died of intercurrent disease. In a multivariate analysis, only stage reached independent prognostic significance for survival (p=0.023).

    In summary, stage represents the most important prognostic factor for survival for uterine and ovarian sarcomas. DNA flow cytometry is useful in gaining additional prognostic information for LMS and ESS. P53-and mdm-2 overexpression had no prognostic value for survival rate. Most of the MMMT overexpressed p53 and were non-diploid. Treatment of sarcomatous neoplasms is difficult and the mainstay remains surgical removal of the tumor. For patients with early stage sarcoma there was a high recurrence rate, which suggests that a large proportion of patients may have systemic micrometastasic disease at the time of diagnosis. Recurrent and metastatic uterine sarcoma remains an incurable disease, and treatment must be considered palliative.

    List of papers
    1. Leiomyosarcoma of the uterus: A clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 49 cases
    Open this publication in new window or tab >>Leiomyosarcoma of the uterus: A clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 49 cases
    Show others...
    1998 (English)In: Gynecologic Oncology, ISSN 0090-8258, Vol. 68, no 1, p. 54-61Article in journal (Refereed) Published
    Abstract [en]

    AIM: The authors analyzed in a retrospective manner the prognostic significance of p53 and mdm-2 expression, DNA ploidy, S-phase fraction (SPF), and traditional clinical and pathological prognostic factors in patients with uterine leiomyosarcomas. MATERIAL: Forty-nine patients were diagnosed with uterine leiomyosarcoma (25 stage I, 4 stage II, 8 stage III, and 12 stage IV). DNA flow cytometric analysis and immunohistochemical staining for p53 and mdm-2 were performed on paraffin-embedded archival tissue from the uterine tumors. RESULTS: Of the 49 patients, 35 (71%) died of disease and 2 died of intercurrent disease. The 5-year survival rate was 33%. FIGO surgical stage, DNA ploidy, SPF, mitotic index, cellular atypia, and tumor grade obtained significance (P < 0.05) in a univariate survival analysis of the leiomyosarcomas. In a multivariate analysis with survival as the end point, stage was found to be the most important factor (P = 0.007); DNA ploidy (P = 0. 045) and SPF (P = 0.041) also had independent prognostic significance. For FIGO stage I tumors, DNA ploidy (P = 0.04) and tumor grade (P = 0.01) were statistically significant in a univariate analysis, while only grade had independent prognostic significance (P = 0.01) in a multivariate analysis. In a univariate analysis including only FIGO stage I and II tumors with disease-free survival as the end point, p53 overexpression (P = 0.0016), DNA ploidy (P = 0.042), and tumor grade (P = 0.008) obtained significance. In a multivariate analysis, only p53 had independent statistical significance (P = 0.01). All p53 immunopositive stage I-II tumors recurred within 28 months from diagnosis. CONCLUSION: This study found that stage represents the most important prognostic factor for uterine leiomyosarcomas. DNA ploidy and SPF had independent prognostic value. DNA flow cytometry is useful in gaining additional prognostic information. In stage I patients, tumor grade gives significant information regarding clinical outcome. In addition, p53 overexpression may predict a higher risk of recurrence in early stage leiomyosarcomas.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13510 (URN)
    Available from: 1999-02-26 Created: 1999-02-26 Last updated: 2009-02-09
    2. Malignant mixed Mullerian tumors of the uterus: a clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 44 cases
    Open this publication in new window or tab >>Malignant mixed Mullerian tumors of the uterus: a clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 44 cases
    Show others...
    1998 (English)In: Gynecologic Oncology, ISSN 0090-8258, Vol. 68, no 1, p. 18-24Article in journal (Refereed) Published
    Abstract [en]

    AIM: The authors retrospectively analyzed the prognostic significance of p53, mdm-2, DNA ploidy, S-phase fraction (SPF), and traditional clinical and pathologic factors in patients with malignant mixed Müllerian tumors (MMMT) of the uterus. METHODS: Between 1970 and 1995, 44 uterine tumors were diagnosed as MMMT (21 stage I, 2 stage II, 10 stage III, and 11 stage IV). Thirty-two were homologous type and 12 were heterologous type. DNA flow cytometry and immunohistochemical analysis for p53 and mdm-2 overexpression were performed on paraffin-embedded archival tissue. RESULTS: 68% of the tumors were nondiploid and 61% had an SPF greater than 10%. Sixty-one percent overexpressed p53 and 25% were mdm-2-positive. Furthermore, 91% of the tumors had a mitotic count greater than 10/10 hpf and 95% had high-grade cytologic atypia. Twenty-seven (61%) patients died of tumor and 6 (14%) died of intercurrent disease. Eleven (25%) patients are alive with no evidence of disease. The median follow-up for patients still alive was 59 months (range, 28-178 months). The overall 5-year survival rate was 38%. In a univariate analysis that included stage, histologic type, DNA ploidy, SPF, p53, mdm-2, mitotic index, and age, and with survival as the end point, only stage reached statistically prognostic significance. CONCLUSION: The majority of the tumors had obvious signs of aggressiveness such as high grade, high mitotic count, nondiploid pattern, high SPF, and overexpression of p53. This study found that stage is the most important prognostic factor for survival in MMMTs of the uterus.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13511 (URN)
    Available from: 1999-02-26 Created: 1999-02-26 Last updated: 2009-02-09
    3. Endometrial stromal sarcoma of the uterus: a clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 17 cases
    Open this publication in new window or tab >>Endometrial stromal sarcoma of the uterus: a clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 17 cases
    1999 (English)In: International Journal of Gynecological Cancer, ISSN 1048-891X, Vol. 9, no 2, p. 98-104Article in journal (Refereed) Published
    Abstract [en]

    Seventeen patients with endometrial stromal sarcoma (ESS) diagnosed between 1970 and 1996 were evaluated according to DNA ploidy, S-phase fraction (SPF), p53, and mdm-2 expression, as well as traditional clinical and pathologic prognostic factors, such as tumor stage, grade, and mitotic index. DNA flow cytometric analysis and immunohistochemical staining for p53 and mdm-2 were performed on paraffin-embedded archival tissue from the uterine tumors. Flow cytometric DNA histograms were obtained from 16 patients.

    The patients ranged in age from 41 to 78 years (median, 57 years). Seven (41%) patients were premenopausal. Thirteen low-grade ESS were DNA diploid and had a low SPF. Of these, two overexpressed p53, while only one was mdm-2 positive. Among the four high-grade ESS we found one (25%) DNA diploid tumor and three (75%) DNA aneuploid tumors. Two (50%) had an SPF greater than 10%, three (75%) were p53-positive, and two (50%) overexpressed mdm-2. During the observation period, nine (53%) patients (five with low-grade and four with high-grade tumors) died of disease. The 5-year survival rate for patients with low-grade ESS was 74%, while all four patients with high-grade ESS died of disease within 14 months of diagnosis. Using the log-rank test, we found a significant correlation between survival and tumor grade (P = 0.007), DNA ploidy (P = 0.026), SPF (P = 0.048), and FIGO surgical stage (P = 0.026).

    In conclusion, we found that tumor grade was a strong predictor of clinical outcome in ESS. In addition, a worse prognosis was found for those ESS patients with advanced disease, DNA aneuploidy, and a high SPF. There was no difference between the recurrent and nonrecurrent group of early stage (surgical stage I), low-grade ESS with regard to clinicopathological features, DNA ploidy, SPF, p53, and mdm-2 expression. All patients with high-grade ESS died of disease within 14 months of diagnosis. In contrast, only three of the 11 patients with early stage, low-grade ESS died of disease.

    Keywords
    DNA ploidy, endometrial stromal sarcoma, mdm-2, p53
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13512 (URN)10.1046/j.1525-1438.1999.09870.x (DOI)
    Available from: 1999-02-26 Created: 1999-02-26 Last updated: 2009-04-28
    4. Adenosarcoma of the uterus: a clinicopathologic, DNA flow cytometric, p53 and mdm-2 analysis of 11 cases
    Open this publication in new window or tab >>Adenosarcoma of the uterus: a clinicopathologic, DNA flow cytometric, p53 and mdm-2 analysis of 11 cases
    1999 (English)In: International Journal of Gynecological Cancer, ISSN 1048-891X, Vol. 9, no 1, p. 37-43Article in journal (Refereed) Published
    Abstract [en]

    Eleven patients with uterine adenosarcoma diagnosed between 1970 and 1995 were evaluated according to DNA ploidy, S-phase fraction, p53 and mdm-2 expression, and traditional clinical and pathological prognostic factors, such as tumor stage, grade and mitotic index. DNA flow cytometric analysis and immunohistochemical staining for p53 and mdm-2 were performed on paraffin-embedded archival tissue from the uterine tumors. The patients ranged in age from 41 to 90 years (median, 76 years). Only one patient was premenopausal at the time of diagnosis and five (45%) were nulliparous. One patient had received previous pelvic irradiation for anal squamous carcinoma. Six of the tumors (55%) were pure adenosarcoma and five (45%) were adenosarcoma with sarcomatous overgrowth. Nine patients had a stage I tumor and two had a stage II tumor. Among the six adenosarcomas we found three DNA diploid tumors, two DNA aneuploid tumors, and one DNA multiploid tumor. All adenosarcomas had an S-phase fraction less than 10%, except one that was not assessable. None was p53 positive and only one overexpressed mdm-2. All five adenosarcomas with sarcomatous overgrowth were DNA aneuploid, three (60%) had an S-phase fraction > 10%, two (40%) were p53 positive, and one (20%) overexpressed mdm-2. Five of the eleven patients suffered recurrences, and three (60%) of these developed lung metastases. During the observation period four (36%) patients (2 adenosarcomas and 2 adenosarcoma with sarcomatous overgrowth) died of disease, three patients died of intercurrent disease without recurrence, and the remaining four are alive with no evidence of disease. The overall five-year survival rate for all stages was 69%; for patients with AS it was 80%, while for those with adenosarcoma with sarcomatous overgrowth it was 50%. There were no variables which correlated with survival. In conclusion, we found hat the typical adenosarcoma had a tendency to be of low stage, have a lower mitotic rate and an S-phase fraction <10%. On the other hand, adenosarcomas with sarcomatous overgrowth were of high grade, had a high mitotic rate, and were DNA aneuploid with an S-phase fraction >10%. None of the variables studied correlated with survival. Tumors that were p53-positive or overexpressed mdm-2 did not behave worse than their negative counterpart. All patients who recurred with distant metastases died of disease.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13513 (URN)
    Available from: 1999-02-26 Created: 1999-02-26 Last updated: 2009-02-09
    5. Malignant mixed Müllerian tumors of the ovary: A clinicopathologic, DNA ploidy and p53 study of 26 cases
    Open this publication in new window or tab >>Malignant mixed Müllerian tumors of the ovary: A clinicopathologic, DNA ploidy and p53 study of 26 cases
    1999 (English)Article in journal (Refereed) Submitted
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13514 (URN)
    Available from: 1999-02-26 Created: 1999-02-26
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  • 163.
    Blom, René
    et al.
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Guerrieri, C.
    Department of Pathology, St. Vincent's Hospital, New York, New York, USA..
    Adenosarcoma of the uterus: a clinicopathologic, DNA flow cytometric, p53 and mdm-2 analysis of 11 cases1999In: International Journal of Gynecological Cancer, ISSN 1048-891X, Vol. 9, no 1, p. 37-43Article in journal (Refereed)
    Abstract [en]

    Eleven patients with uterine adenosarcoma diagnosed between 1970 and 1995 were evaluated according to DNA ploidy, S-phase fraction, p53 and mdm-2 expression, and traditional clinical and pathological prognostic factors, such as tumor stage, grade and mitotic index. DNA flow cytometric analysis and immunohistochemical staining for p53 and mdm-2 were performed on paraffin-embedded archival tissue from the uterine tumors. The patients ranged in age from 41 to 90 years (median, 76 years). Only one patient was premenopausal at the time of diagnosis and five (45%) were nulliparous. One patient had received previous pelvic irradiation for anal squamous carcinoma. Six of the tumors (55%) were pure adenosarcoma and five (45%) were adenosarcoma with sarcomatous overgrowth. Nine patients had a stage I tumor and two had a stage II tumor. Among the six adenosarcomas we found three DNA diploid tumors, two DNA aneuploid tumors, and one DNA multiploid tumor. All adenosarcomas had an S-phase fraction less than 10%, except one that was not assessable. None was p53 positive and only one overexpressed mdm-2. All five adenosarcomas with sarcomatous overgrowth were DNA aneuploid, three (60%) had an S-phase fraction > 10%, two (40%) were p53 positive, and one (20%) overexpressed mdm-2. Five of the eleven patients suffered recurrences, and three (60%) of these developed lung metastases. During the observation period four (36%) patients (2 adenosarcomas and 2 adenosarcoma with sarcomatous overgrowth) died of disease, three patients died of intercurrent disease without recurrence, and the remaining four are alive with no evidence of disease. The overall five-year survival rate for all stages was 69%; for patients with AS it was 80%, while for those with adenosarcoma with sarcomatous overgrowth it was 50%. There were no variables which correlated with survival. In conclusion, we found hat the typical adenosarcoma had a tendency to be of low stage, have a lower mitotic rate and an S-phase fraction <10%. On the other hand, adenosarcomas with sarcomatous overgrowth were of high grade, had a high mitotic rate, and were DNA aneuploid with an S-phase fraction >10%. None of the variables studied correlated with survival. Tumors that were p53-positive or overexpressed mdm-2 did not behave worse than their negative counterpart. All patients who recurred with distant metastases died of disease.

  • 164.
    Blom, René
    et al.
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Guerrieri, C.
    Department of Pathology, St. Vincent's Hospital, New York, New York, USA.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Malmström, Helena
    Linköping University, Department of Molecular and Clinical Medicine.
    Simonsen, E.
    Leiomyosarcoma of the uterus: A clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 49 cases1998In: Gynecologic Oncology, ISSN 0090-8258, Vol. 68, no 1, p. 54-61Article in journal (Refereed)
    Abstract [en]

    AIM: The authors analyzed in a retrospective manner the prognostic significance of p53 and mdm-2 expression, DNA ploidy, S-phase fraction (SPF), and traditional clinical and pathological prognostic factors in patients with uterine leiomyosarcomas. MATERIAL: Forty-nine patients were diagnosed with uterine leiomyosarcoma (25 stage I, 4 stage II, 8 stage III, and 12 stage IV). DNA flow cytometric analysis and immunohistochemical staining for p53 and mdm-2 were performed on paraffin-embedded archival tissue from the uterine tumors. RESULTS: Of the 49 patients, 35 (71%) died of disease and 2 died of intercurrent disease. The 5-year survival rate was 33%. FIGO surgical stage, DNA ploidy, SPF, mitotic index, cellular atypia, and tumor grade obtained significance (P < 0.05) in a univariate survival analysis of the leiomyosarcomas. In a multivariate analysis with survival as the end point, stage was found to be the most important factor (P = 0.007); DNA ploidy (P = 0. 045) and SPF (P = 0.041) also had independent prognostic significance. For FIGO stage I tumors, DNA ploidy (P = 0.04) and tumor grade (P = 0.01) were statistically significant in a univariate analysis, while only grade had independent prognostic significance (P = 0.01) in a multivariate analysis. In a univariate analysis including only FIGO stage I and II tumors with disease-free survival as the end point, p53 overexpression (P = 0.0016), DNA ploidy (P = 0.042), and tumor grade (P = 0.008) obtained significance. In a multivariate analysis, only p53 had independent statistical significance (P = 0.01). All p53 immunopositive stage I-II tumors recurred within 28 months from diagnosis. CONCLUSION: This study found that stage represents the most important prognostic factor for uterine leiomyosarcomas. DNA ploidy and SPF had independent prognostic value. DNA flow cytometry is useful in gaining additional prognostic information. In stage I patients, tumor grade gives significant information regarding clinical outcome. In addition, p53 overexpression may predict a higher risk of recurrence in early stage leiomyosarcomas.

  • 165.
    Blom, René
    et al.
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Guerrieri, C.
    Department of Pathology, St. Vincent's Hospital, New York, New York, USA.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Malmström, Helena
    Linköping University, Department of Molecular and Clinical Medicine.
    Sullivan, S.
    Simonsen, E.
    Malignant mixed Mullerian tumors of the uterus: a clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 44 cases1998In: Gynecologic Oncology, ISSN 0090-8258, Vol. 68, no 1, p. 18-24Article in journal (Refereed)
    Abstract [en]

    AIM: The authors retrospectively analyzed the prognostic significance of p53, mdm-2, DNA ploidy, S-phase fraction (SPF), and traditional clinical and pathologic factors in patients with malignant mixed Müllerian tumors (MMMT) of the uterus. METHODS: Between 1970 and 1995, 44 uterine tumors were diagnosed as MMMT (21 stage I, 2 stage II, 10 stage III, and 11 stage IV). Thirty-two were homologous type and 12 were heterologous type. DNA flow cytometry and immunohistochemical analysis for p53 and mdm-2 overexpression were performed on paraffin-embedded archival tissue. RESULTS: 68% of the tumors were nondiploid and 61% had an SPF greater than 10%. Sixty-one percent overexpressed p53 and 25% were mdm-2-positive. Furthermore, 91% of the tumors had a mitotic count greater than 10/10 hpf and 95% had high-grade cytologic atypia. Twenty-seven (61%) patients died of tumor and 6 (14%) died of intercurrent disease. Eleven (25%) patients are alive with no evidence of disease. The median follow-up for patients still alive was 59 months (range, 28-178 months). The overall 5-year survival rate was 38%. In a univariate analysis that included stage, histologic type, DNA ploidy, SPF, p53, mdm-2, mitotic index, and age, and with survival as the end point, only stage reached statistically prognostic significance. CONCLUSION: The majority of the tumors had obvious signs of aggressiveness such as high grade, high mitotic count, nondiploid pattern, high SPF, and overexpression of p53. This study found that stage is the most important prognostic factor for survival in MMMTs of the uterus.

  • 166.
    Blom, René
    et al.
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Malmström, Henric
    Guerrieri, Claudio
    Department of Pathology, St. Vincent's Hospital, New York, USA .
    Endometrial stromal sarcoma of the uterus: a clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 17 cases1999In: International Journal of Gynecological Cancer, ISSN 1048-891X, Vol. 9, no 2, p. 98-104Article in journal (Refereed)
    Abstract [en]

    Seventeen patients with endometrial stromal sarcoma (ESS) diagnosed between 1970 and 1996 were evaluated according to DNA ploidy, S-phase fraction (SPF), p53, and mdm-2 expression, as well as traditional clinical and pathologic prognostic factors, such as tumor stage, grade, and mitotic index. DNA flow cytometric analysis and immunohistochemical staining for p53 and mdm-2 were performed on paraffin-embedded archival tissue from the uterine tumors. Flow cytometric DNA histograms were obtained from 16 patients.

    The patients ranged in age from 41 to 78 years (median, 57 years). Seven (41%) patients were premenopausal. Thirteen low-grade ESS were DNA diploid and had a low SPF. Of these, two overexpressed p53, while only one was mdm-2 positive. Among the four high-grade ESS we found one (25%) DNA diploid tumor and three (75%) DNA aneuploid tumors. Two (50%) had an SPF greater than 10%, three (75%) were p53-positive, and two (50%) overexpressed mdm-2. During the observation period, nine (53%) patients (five with low-grade and four with high-grade tumors) died of disease. The 5-year survival rate for patients with low-grade ESS was 74%, while all four patients with high-grade ESS died of disease within 14 months of diagnosis. Using the log-rank test, we found a significant correlation between survival and tumor grade (P = 0.007), DNA ploidy (P = 0.026), SPF (P = 0.048), and FIGO surgical stage (P = 0.026).

    In conclusion, we found that tumor grade was a strong predictor of clinical outcome in ESS. In addition, a worse prognosis was found for those ESS patients with advanced disease, DNA aneuploidy, and a high SPF. There was no difference between the recurrent and nonrecurrent group of early stage (surgical stage I), low-grade ESS with regard to clinicopathological features, DNA ploidy, SPF, p53, and mdm-2 expression. All patients with high-grade ESS died of disease within 14 months of diagnosis. In contrast, only three of the 11 patients with early stage, low-grade ESS died of disease.

  • 167. Blomgren, J
    et al.
    Ekman, Bertil
    Andersson, P-O
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Non-physiological levels of circulating cortisol in growth hormone-treated hypopituitary adults after conventional cortisone substitution2004In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 64, no 2, p. 132-139Article in journal (Refereed)
    Abstract [en]

    Objective: To assess the usefulness of measuring plasma cortisol profiles in growth hormone-treated hypopituitary adults and to compare these with cortisol levels in healthy controls. Methods: Eleven ACTH-deficient adult patients received 12.5 mg cortisone-acetate orally at 16.00 h and 25 mg at 07.00 h. The patients arrived in the ward at 12.00 h. After tablet intake at 16.00 h, samples for serum cortisol were taken at hourly intervals for the next 24 h, except between 07.00 and 12.00 h when samples were drawn every half hour, 24-h urinary free cortisol (24-h-UFC) excretion was collected simultaneously. For comparison, 8 healthy controls were investigated. Results: The patients had circulating cortisol levels with very low plasma cortisol at 07.00 h before their morning dose of cortisone acetate. At the same time period, controls had their highest plasma cortisol levels. After tablet intake the patients had a rapid initial absorption of cortisol, but a marked variability in the morning peak levels (Cmax), and the Cmax was in general higher and occurred 90 min later than the Cmax in the controls. The 24-h-UFC excretion and 24-h area under the curve (24-h-AUC) did not differ between patients and controls. The female patients had higher 24-h-AUC for plasma cortisol (p=0.032) and tended to have higher plasma cortisol peaks in the morning, but had levels of 24-h-UFC similar to those of the male patients. Conclusions: Conventional cortisone substitution with a twice-daily replacement regimen in hypopituitary adults results in abnormal circulating cortisol profiles with low or non-measurable morning values and variable individual peaks. This suggests that the present dosing schemes have to be improved and that cortisone substitution should be individualized.

  • 168. Blomquist, L.
    et al.
    Dizdar, N.
    Linköping University, Department of Biomedicine and Surgery.
    Karlsson, M.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemestry. Linköping University, Faculty of Health Sciences.
    Ossowicki, H.
    Pettersson, A.
    Smeds, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Microdialysis of 5-S-cysteinyldopa from interstitial fluid in cutaneous human melanoma transplanted to athymic mice1991In: Melanoma Research, ISSN 0960-8931, Vol. 1, no 1, p. 23-32Article in journal (Refereed)
    Abstract [en]

    Microdialysis was investigated as a tool for the determination of the extracellular concentration of the pigment metabolite 5-S-cysteinyldopa in human melanoma transplanted to athymic mice. Histology of the tumour with the microdialysis probes in situ showed no tissue damage. With probes equipped with polycarbonate membranes (20 kD) extraction (relative recovery) was approximately 50% at pH 4.0 and flow rates of 1 microliter/min, but at pH 7.0 recoveries were markedly lower, particularly from serum. In a first series of human melanomas transplanted to athymic mice low concentrations of 5-S-cysteinyldopa were detected in only two out of ten dialysates and were not detected in the other eight. Utilizing devices constructed for comparison of membrane characteristics in vitro we found about 4-fold higher recoveries with cuprophane and polyamide membranes than with polycarbonate membranes. Therefore newly constructed microdialysis probes (CMA/11) with cuprophane membranes were tested in vitro and gave recoveries of 38-48% from Ringer-Acetate solutions and 22-31% from serum, and the pH effects were low. When these probes were utilized in a second series of melanomas transplanted to athymic mice, 5-S-cysteinyldopa could easily be quantified in 10/10 experiments. A steady-state level of the dialysate 5-S-cysteinyldopa concentration was reached after 45 min.

  • 169.
    Blomqvist, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Acta Gyllenbergiana IV.Psyche, soma and pain.Editors Eija Kalso, Ann-Mari Estlander and Matti Klockars.2003In: Skriv in din egen text för ej reg. tidskrift etc.,2003, 2003, p. 59-72Conference paper (Refereed)
  • 170.
    Blomqvist, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Sex hormones and pain: A new role for brain aromatase?2000In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 423, no 4, p. 549-551Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 171.
    Blomqvist, Anders
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Craig, A D (Bud)
    Is neuropathic pain caused by the activation of nociceptive-specific neurons due to anatomic sprouting in the dorsal horn?2000In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 428, no 1Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 172.
    Blomqvist, Anders
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Zhang, En-Tan
    Craig, A D (Bud)
    Cytoarchitectonic and immunohistochemical characterization of a specific pain and temperature relay, the posterior portion of the ventral medial nucleus, in the human thalamus2000In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 123, no 3, p. 601-619Article in journal (Refereed)
    Abstract [en]

    Previous studies in the macaque monkey have identified a thalamic nucleus, the posterior portion of the ventral medial nucleus (VMpo), as a dedicated lamina I spinothalamocortical relay for pain and temperature sensation. The dense plexus of calbindin-immunoreactive fibres that characterizes VMpo in primates enables its homologue to be identified in the human thalamus by immunohistochemical labelling for calbindin. We have now analysed in detail the cytoarchitectonic characteristics of VMpo and its relationship with immunoreactivity for calbindin, substance P and calcitonin gene-related peptide (CGRP) in the human thalamus. The area in the posterolateral thalamus in which dense calbindin-immunoreactive fibre terminations are present coincides nearly completely with a distinct region that contains small to medium-sized cells with round or oval shapes that are aggregated in clusters separated by cell sparse areas. This region, which we identify as VMpo, is located posteromedial to the ventral posterior lateral (VPL) and ventral posterior medial (VPM) nuclei, ventral to the anterior pulvinar and centre median nuclei, lateral to the limitans and parafascicular nuclei and dorsal to the medial geniculate nucleus. Calbindin-immunoreactive fibres enter VMpo from the spinal lemniscus and form large patches of dense terminal-like staining over clusters of VMpo neurons. A few of these clusters also display terminal-like substance P labelling. Small bursts of CGRP staining are intercalated between the calbindin-labelled clusters, but there is little or no overlap between these two markers. CGRP inmunoreactivity is also present over small, non-clustered neurons in the calbindin-negative area that separates VMpo from the VPL and VPM nuclei, which we denote as the posterior nucleus (Po). These observations provide a concise description of VMpo in the human thalamus. Further, they suggest that the lamina I spinothalamic tract fibres (represented by calbindin and probably also substance P immunoreactivity) and vagal-solitary-parabrachial afferents (represented by CGRP immunoreactivity) form closely related, but separate, termination fields that can be considered to represent different aspects of enteroceptive information regarding the physiological status of the tissues and organs of the body. The location of VMpo and the adjacent Po fits with clinical descriptions of the thalamic area from which pain, temperature and visceral sensations can be evoked by microstimulation, and where nociceptive and thermoreceptive neurons have been recorded in humans. It also corresponds to the area in which infarcts cause analgesia and thermoanaesthesia and can lead to the paradoxical development of central pain.

  • 173. Blomqvist, P
    et al.
    Lycke, J
    Strang, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Palliative mediicin. Östergötlands Läns Landsting, ViN, LAH Linnea.
    Törnqvist, H
    Ekbom, A
    Brain tumours in Sweden 1996: care and costs.2000In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 69, p. 792-798Article in journal (Refereed)
  • 174. Boalth, Nicolas
    et al.
    Wandrup, Jesper
    Larsson, Lasse
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Frischauf, Peter
    Lundsgaard, Finn
    Andersen, Willy
    Jensen, Niels-Henrik
    Singer, Rolf
    Troldborg, Carl
    Lunding, Gitte
    Blood gases and oximetry: calibration-free new dry-chemistry and optical technology for near-patíent testing.2001In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 307, p. 225-233Article in journal (Refereed)
  • 175.
    Bobinski, L
    et al.
    Neurokirurgisk klinik Rekonstruktionscentrum.
    Boström, Sverre
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Hillman, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Theodorsson, Annette
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Postoperative pseudoaneurysm of the superficial temporal artery (S.T.A.) treated with Thrombostat® (thrombin glue) injection2004In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 146, no 9, p. 1039-1041Article in journal (Refereed)
    Abstract [en]

    Background. Pseudo-aneurysm is a rare complication of craniotomy. Blunt injury to the temporal artery region is the usual cause, but still a rare complication. Clinical presentation. A patient with subarachnoid hemorrhage was successfully treated by aneurysm clipping. The patient developed hydrocephalus, and was admitted for a shunt operation seventeen days later. The craniotomy had healed normally, but a palpable temporal lump was present in the skin incision. Intervention. The pulsating mass proved to be a postoperative aneurysm of the superficial temporal artery (S.T.A.) and was successfully occluded with 500 units Thrombostat® (thrombin glue) which was injected into the aneurysm sac using a 22-gauge needle guided by ultrasound. The permanency of the obliteration was verified by ultrasound examination.

  • 176. Bobinski, L
    et al.
    Boström, Sverre
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Zsigmond, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Theodorsson, Annette
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Leptomeningeal cyst due to vacuum extraction delivery in a twin infant2007In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 149, no 3, p. 319-323Article in journal (Refereed)
    Abstract [en]

    A rare case of a leptomeningeal cyst is reported in a twin male neonate delivered using a vacuum extractor, who presented a huge, non-pulsating, oedematous mass overlying the frontal fontanelle after birth. The mass was initially diagnosed as a cephalo haematoma. Ultrasonography indicated intracranial bleeding and a subsequent CT scan revealed an intraparenchymal bleeding above the left frontal horn, combined with a thin, left-sided, subdural haematoma and subarachnoid haemorrhage in the left Sylvian fissure. Apart from a bulging soft and round formation (2 × 2 × 3 cm) next to the anterior fontanel growing since birth, the neurological development of the infant was normal. MRI examination at the age of 7 months revealed that it consisted of a cystic mass (leptomeningeal cyst) connected to the left frontal horn, stretching right through the brain and also penetrating the dura mater. No signs of the perinatal haematomas were observed at this time. Surgical treatment, with fenestration of the cyst into the frontal horn and a watertight duraplasty with a periosteal flap and thrombin glue covered by small bone chips, was performed at 9 months of age. Due to a residual skull bone defect a second cranioplasty with autologous skull bone was performed three and half years later. During a follow-up period of 12 years the neurological and psychological development of the boy has been indistinguishable to that of his twin brother, indicating the satisfactory outcome of the treatment. © 2007 Springer-Verlag.

  • 177. Bohe, Måns
    et al.
    Cedermark, Björn
    Damber, Lena
    Lewin, Freddi
    Lindmark, Gudrun
    Nordgren, Svante
    Påhlman, Lars
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Kvalitetsregister etablerat för bättre rektalcancerbehandling.2000In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 97, p. 3587-3591Article in journal (Other (popular science, discussion, etc.))
  • 178. Bojestig, M
    et al.
    Nyström, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Karlberg, Bengt E
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    The renin-angiotensin-aldosterone system is suppressed in adults with Type 1 diabetes2000In: jraas. Journal of the renin-angiotensin-aldosterone system, ISSN 1470-3203, E-ISSN 1752-8976, Vol. 1, no 4, p. 353-356Article in journal (Refereed)
    Abstract [en]

    Poor glycaemic control and high blood pressure are two important risk factors for the development of retinopathy and nephropathy in Type 1 diabetes. The renin-angiotensin-aldosterone system (RAAS) may be involved in this process, since treatment with angiotensin-converting enzyme (ACE) inhibitors postpones the development of these complications. We investigated whether plasma renin activity (PRA), plasma angiotensin II (Ang II) and atrial natriuretic peptide (ANP) differed in Type 1 diabetic patients compared with healthy controls. We recruited 80 patients with Type 1 diabetes of more than 10 years' duration and 75 age-matched controls. We found that PRA and Ang II concentrations were significantly lower in patients than in the controls. The levels of ANP, on the other hand, were higher in patients than in controls. PRA correlated negatively to the mean value of HbA1c during the previous five years. PRA and Ang II were significantly lower in patients with mean HbA1c. >8.4% compared with those with mean HbA1c 7.2%. In summary, we found patients with Type 1 diabetes to have RAAS suppression and increased ANP levels, suggesting a state of fluid retention.

  • 179. Bolinder, J
    et al.
    Fernlund, P
    Borg, H
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Björk, E
    Blohmé, G
    Eriksson, JW
    Nyström, L
    Östman, J
    Sundkvist, G
    Hyperproinsulinemia segregates young adult patients with newly diagnosed autoimmune (type 1) and non-autoimmune (type 2) diabetes2005In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 65, no 7, p. 585-594Article in journal (Refereed)
    Abstract [en]

    Objective. To investigate whether measurements of proinsulin and/or intermediate proinsulin degradation products could be used to differentiate between autoimmune (type 1) and non-autoimmune (type 2) diabetes in young adults. Material and methods. Total proinsulin, intact proinsulin and 32,33 split proinsulin concentrations were measured in 25 patients aged 15-34 years with type 1 diabetes, as defined by the presence of at least two positive islet autoantibodies, and in 23 antibody-negative patients of similar age with type 2 diabetes, at the time of clinical onset of diabetes and at 3-4 months thereafter. Comparisons were made with data from 25 healthy subjects matched for gender and age. Results. Plasma levels of total proinsulin, intact proinsulin and 32,33 split proinsulin were significantly increased 2-3-fold in the patients with newly diagnosed type 2 diabetes as compared with the controls, both in absolute terms (p<0.0001) and when related to circulating insulin (p<0.01-0.0002). In contrast, absolute proinsulin and 32,33 split proinsulin concentrations were significantly lower in patients with onset of type 1 diabetes than in controls. When proinsulin and split proinsulin release were related to plasma insulin, however, similar ratios were found in the type 1 diabetes patients and in controls. Using the 90th percentile for total proinsulin in the control group as the cut-off, the sensitivity and specificity for differentiation between autoimmune and non-autoimmune diabetes were 87% and 92%, respectively. At 3-4 months after clinical onset of diabetes, proinsulin secretion was still 2-3 times higher in type 2 than in type 1 diabetes patients (p<0.001). Conclusions. Young adult patients with newly diagnosed type 2 diabetes display disproportionate hyperproinsulinemia, whereas proinsulin secretion appears to be normal in patients with clinical onset of type 1 diabetes. Evaluation of proinsulin and 32,33 split proinsulin concentrations may be useful as a diagnostic tool in differentiating between autoimmune and non-autoimmune diabetes in young adults, particularly in those lacking islet autoantibodies at diagnosis. © 2005 Taylor & Francis.

  • 180.
    Bolling-Sternevald, E
    et al.
    Linkoping Univ Hosp, Dept Biomed & Surg, S-58185 Linkoping, Sweden AstraZeneca R&D, Molndal, Sweden Odense Univ Hosp, Dept Gastroenterol, DK-5000 Odense, Denmark.
    Carlsson, R
    Aalykke, C
    Linkoping Univ Hosp, Dept Biomed & Surg, S-58185 Linkoping, Sweden AstraZeneca R&D, Molndal, Sweden Odense Univ Hosp, Dept Gastroenterol, DK-5000 Odense, Denmark.
    Wilson, B
    Linkoping Univ Hosp, Dept Biomed & Surg, S-58185 Linkoping, Sweden AstraZeneca R&D, Molndal, Sweden Odense Univ Hosp, Dept Gastroenterol, DK-5000 Odense, Denmark.
    Junghard, O
    Linkoping Univ Hosp, Dept Biomed & Surg, S-58185 Linkoping, Sweden AstraZeneca R&D, Molndal, Sweden Odense Univ Hosp, Dept Gastroenterol, DK-5000 Odense, Denmark.
    Lauritsen, K
    Linkoping Univ Hosp, Dept Biomed & Surg, S-58185 Linkoping, Sweden AstraZeneca R&D, Molndal, Sweden Odense Univ Hosp, Dept Gastroenterol, DK-5000 Odense, Denmark.
    Glise, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery.
    Gastrointestinal (GI) symptoms, quality of life and endoscopic diagnoses in patients with upper GI symptoms2001In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 120, no 5, p. 1248-Conference paper (Other academic)
  • 181. Order onlineBuy this publication >>
    Bolling-Sternevald, Elisabeth
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Functional Dyspepsia: Symptoms and Response to Omeprazole in the Short Term2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Gastrointestinal symptoms have a prevalence of 20-40% in the general adult population in the Western world. These symptoms are generally considered to be poor predictors of organic findings [e.g. peptic ulcer disease (PUD) or malignancy]. Approximately 50% of patients seeking care for such symptoms have no organic explanation for these upon investigation. When other organic or other functional conditions are excluded [e.g. PUD, gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS)] the remaining patients are labelled as having functional dyspepsia (persistent or recurrent pain and/or discomfort centred in the upper abdomen). Management of functional dyspepsia remains a challenge, reflecting the heterogeneity of the patients and the uncertain role of drug treatment. Also, prognostic factors for treatment success are largely unknown. I have therefore performed a series of studies to shed light on these issues: The first study (Paper I) was performed in a randomly selected adult population (n=1,001) assessing upper and lower gastrointestinal symptoms at two occasions with 1 to 6 month intervals. The results show that gastrointestinal symptoms are common (57%) and fluctuate to some extent in the shorter term. Troublesome dyspeptic symptoms remain in two out of three individuals. This proportion was similar whether or not organic findings were present. In the second study (Paper II) 799 patients with dyspeptic symptoms were evaluated with regard to whether gastrointestinal symptoms, identified by self-administered questionnaires, correlate with endoscopic diagnoses and discriminate organic from non-organic (functional) dyspepsia. The impact of dyspeptic symptoms on health-related well-being was also evaluated. Approximately 50% of these dyspeptic patients were found to have functional dyspepsia at upper endoscopy. A difference was discovered in the symptom profile between patients with organic and functional dyspepsia. Predicting factors for functional dyspepsia were found. This study shows that use of self-administered symptom questionnaires may aid in clinical decision making for patient management, e.g. by reducing the number of endoscopies, although probabilities of risks for organic dyspepsia are difficult to transfer to management of the individual patient. The results also indicate that the health-related well-being in patients with functional and organic dyspepsia is impaired to the same extent, illustrating the need for effective treatment of patients with functional dyspepsia, a group not well served by currently available treatment modalities. The aim of the third study (Paper III) was to develop and evaluate a selfadministered questionnaire focusing on upper abdominal and reflux complaints to allow for identification of patients with heartburn and factors that might predict symptom relief with omeprazole both in GERD and functional dyspepsia patients. The diagnostic validity of the questionnaire was tested against endoscopy and 24-hour pH monitoring. The questionnaire had a sensitivity of 92%, but a low specificity of 19%. Symptom relief by omeprazole was best predicted by the presence of predominant heartburn described as ‘a burning feeling rising from the stomach or lower chest up towards the neck’ and ‘relief from antacids’. These results indicate that this questionnaire which used descriptive language, appeared to be useful in identifying heartburn and predicting responses to omeprazole in patients with upper gastrointestinal symptoms. The fourth study (Paper IV) was a pilot study investigating the symptom response to omeprazole 20 mg twice daily or placebo for a duration of 14 days in 197 patients with functional dyspepsia. We concluded that a subset of patients with functional dyspepsia, with or without heartburn, would respond to therapy with omeprazole. In the final study (Paper V) the aim was to identify prognostic factors for the treatment success to a 4-week course of omeprazole 10 or 20 mg once daily in 826 patients with functional dyspepsia. The most highly discriminating predictor of treatment success was the number of days without dyspeptic symptoms during the first week of treatment. Fewer days with symptoms during the first week indicated higher response rates at four weeks. In addition, positive predictors of treatment response to omeprazole were identified as age >40 years, bothersome heartburn, low scores of bloating and diarrhoea, history of symptoms for <3 months and low impairment of vitality at baseline. The results indicate that early response during the first week to treatment with a proton pump inhibitor seems to predict treatment success after four weeks in patients with functional dyspepsia. Conclusion: These studies have shown that a large proportion of adult individuals in society, both those who seek and those who do not seek medical care, suffer from symptoms located in the upper part of the abdomen regardless of whether an organic cause is present. A subset of patients without organic findings and other functional conditions, i.e. functional dyspepsia, respond to therapy with omeprazole irrespective of the presence or absence of heartburn . An excellent way to predict the response to a full course of omeprazole in functional dyspepsia is to assess the early response (first week) to treatment. These findings allow for better and faster targeting of acid inhibitory therapy in functional dyspepsia, which potentially can result in more effective clinical management of these patients and savings of health care resources.

    List of papers
    1. Gastro-oesophageal reflux symptoms and health-related quality of life in the adult general population--the Kalixanda study
    Open this publication in new window or tab >>Gastro-oesophageal reflux symptoms and health-related quality of life in the adult general population--the Kalixanda study
    Show others...
    2006 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 23, no 12, p. 1725-1733Article in journal (Refereed) Published
    Abstract [en]

    Background

    The impact of gastro-oesophageal reflux symptoms on health-related quality of life in the general population is poorly characterized.

    Aim

    To identify the frequency of troublesome reflux symptoms associated with impaired health-related quality of life in the general population.

    Methods

    A representative random sample of 3000 adult inhabitants of northern Sweden was surveyed using the validated Abdominal Symptom Questionnaire (response rate 74%). In total, 1001 random responders were endoscoped and assessed using the Short Form-36 Health Survey.

    Results

    Complete data were obtained for 999 subjects: 6% reported reflux symptoms (heartburn and/or regurgitation) daily, 14% weekly and 20% less than weekly during the previous 3 months. Compared with no reflux symptoms, a clinically relevant impairment of health-related quality of life (≥5 points and P < 0.05) was seen in all eight Short Form-36 dimensions for daily symptoms, in five dimensions for weekly symptoms and in one dimension for less than weekly symptoms. There were no meaningful differences in Short Form-36 scores between subjects with and without oesophagitis.

    Conclusions

    Most aspects of health-related quality of life were impaired in individuals with daily or weekly reflux symptoms. Troublesome reflux symptoms at least weekly may identify gastro-oesophageal reflux disease.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13684 (URN)10.1111/j.1365-2036.2006.02952.x (DOI)
    Available from: 2003-06-15 Created: 2003-06-15 Last updated: 2017-12-13
    2. Self-administered symptom questionnaires in patients with dyspepsia and their yield in discriminating between endoscopic diagnoses
    Open this publication in new window or tab >>Self-administered symptom questionnaires in patients with dyspepsia and their yield in discriminating between endoscopic diagnoses
    Show others...
    2002 (English)In: Digestive diseases, Vol. 20, no 2, p. 191-198Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND/AIMS: Symptoms are generally considered to be poor predictors of organic findings in patients with dyspepsia. We aimed at evaluating whether specific gastrointestinal symptoms, identified by self-administered questionnaires, correlate with specific endoscopic diagnoses and discriminate organic from functional dyspepsia. METHODS: Adult patients with pain or discomfort centred in the upper abdominal region were consecutively enrolled. Patients with heartburn, acid regurgitation, or defaecation and bowel habit problems as their predominant symptoms were excluded. Three self-administered questionnaires were applied before an oesophagogastroduodenoscopy was performed. RESULTS: Among the 799 patients, 50.6% had a normal endoscopy. Endoscopic diagnoses comprised: non-erosive oesophagitis (7.5%), erosive oesophagitis (11.1%), Barrett's oesophagus (1.1%), gastritis/duodenitis (8.4%), gastric ulcer (4.5%), duodenal ulcer (8.3%), and cancer (1.3%). Non-dominant heartburn and acid regurgitation were significantly more common in patients with organic dyspepsia, whereas hunger pains and rumbling occurred more often in those with functional dyspepsia. Multivariate analyses demonstrated that younger age, female gender, high scores for hunger pain, rumbling, hard stools, low scores for heartburn, and acid regurgitation predicted functional dyspepsia. CONCLUSIONS: Self-administered questionnaires revealed differences in the symptom patterns between patients with functional and organic dyspepsia. Furthermore, the health-related well-being in patients with functional and organic dyspepsia centred was impaired to the same extent.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13685 (URN)10.1159/000067482 (DOI)
    Available from: 2003-06-15 Created: 2003-06-15 Last updated: 2009-10-31
    3. The usefulness of a structured questionnaire in the assessment of symptomatic gastroesophageal reflux disease
    Open this publication in new window or tab >>The usefulness of a structured questionnaire in the assessment of symptomatic gastroesophageal reflux disease
    Show others...
    1998 (English)In: Scandinavian journal of gastroenterology, ISSN 0036-5521, Vol. 33, no 10, p. 1023-1029Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: The diagnosis of gastroesophageal reflux disease (GERD) rests primarily on recognition of symptom patterns that are classical for reflux disease, but little attention has been paid to the use of a formal questionnaire for identifying such symptom patterns. METHODS: A self-administered questionnaire was developed which has seven items that focus on the nature of the symptoms and the precipitating, exacerbating, and relieving factors. The diagnostic validity of the questionnaire was tested against endoscopy and 24-h pH monitoring. A further evaluation was undertaken in patients with symptoms suggestive of GERD and in patients with non-ulcer dyspepsia, to identify factors that might predict symptom relief during treatment with omeprazole. RESULTS: When endoscopic esophageal mucosal breaks and 24-h pH data were used as criteria for the diagnosis of GERD, the questionnaire had a sensitivity of 92% but a very low specificity of 19%. Symptom relief during treatment with omeprazole was predicted by the presence of heartburn, described as 'a burning feeling rising from the stomach or lower chest up towards the neck' (P = 0.004), and 'relief from antacids' (P = 0.02). In non-ulcer dyspepsia a positive response to omeprazole was confined to the subgroup of patients who identified their main discomfort as heartburn as described above. CONCLUSION: The present questionnaire using descriptive language usefully identified heartburn in patients presenting with upper abdominal symptoms, and this symptom predicted symptom resolution during treatment with omeprazole.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13686 (URN)
    Available from: 2003-06-15 Created: 2003-06-15
    4. Effect of Profound Acid Suppression in Functional Dyspepsia: a Double-Blind, Randomized, Placebo-Controlled Trial
    Open this publication in new window or tab >>Effect of Profound Acid Suppression in Functional Dyspepsia: a Double-Blind, Randomized, Placebo-Controlled Trial
    Show others...
    2002 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 37, no 12, p. 1395-1402Article in journal (Refereed) Published
    Abstract [en]

    Background: Functional dyspepsia (FD) is defined as persistent or recurrent pain/discomfort centred in the upper abdomen, where no structural explanation for the symptoms is found. The role of drug treatment remains controversial. The aim in this study was to evaluate the effect of omeprazole 20 mg twice daily (b.i.d) and to test methods for symptom assessment.

    Methods: 197 patients fulfilling the criteria for FD were randomly allocated to double-blind treatment with omeprazole 20 mg b.i.d ( n = 100) or placebo ( n = 97) for 14 days. Patients with a known gastrointestinal disorder or with main symptoms indicating gastro-oesophageal reflux disease or irritable bowel syndrome were excluded. Helicobacter pylori testing and 24-h intra-oesophageal 24-h pH-metry were performed before randomization. The patients recorded dyspeptic symptoms on diary cards.

    Results: A stringent endpoint, 'complete symptom relief on the last day of treatment', was the primary efficacy variable. For the APT cohort, this was achieved in 29.0% and 17.7% on omeprazole and placebo, respectively (95% CI of difference (11.3%): -0.4%-23.0%, P = 0.057). Similar figures in the PP cohort were 31.0% and 15.5%, respectively (95% CI of difference (15.5%): 3.2%-27.7%, P = 0.018). The benefit of omeprazole in the PP cohort was confirmed by secondary endpoints such as, no dyspeptic symptoms on the last 2 days of treatment and overall treatment response. H. pylori status and the level of oesophageal acid exposure did not significantly influence the response to therapy.

    Conclusion: A subset of patients with FD will respond to therapy with omeprazole.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13687 (URN)10.1080/003655202762671260 (DOI)
    Available from: 2003-06-15 Created: 2003-06-15 Last updated: 2017-12-13Bibliographically approved
    5. Is it possible to predict treatment response to a proton pump inhibitor in functional dyspepsia?
    Open this publication in new window or tab >>Is it possible to predict treatment response to a proton pump inhibitor in functional dyspepsia?
    Show others...
    2003 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 18, no 1, p. 117-124Article in journal (Refereed) Published
    Abstract [en]

    Background: The efficacy of proton pump inhibitors in functional dyspepsia is modest and the prognostic factors are almost unknown.

    Methods: Data were pooled on patients (n = 826) with a diagnosis of functional dyspepsia from two placebo-controlled trials who were treated with omeprazole, 10 or 20 mg once daily, for 4 weeks. Self-administered questionnaires for the assessment of symptoms and health-related quality of life were completed before entry, and epigastric pain/discomfort was recorded on diary cards. Treatment success was defined as the complete absence of epigastric pain/discomfort on each of the last 3 days of week 4. Prognostic factors were identified by multiple logistic regression analysis.

    Results: The most discriminating predictor of treatment success (P < 0.0001) was the number of days with epigastric pain/discomfort during the first week of treatment. Fewer days with symptoms during the first week led to higher response rates at 4 weeks. In addition, age > 40 years, bothersome heartburn, low scores for bloating, epigastric pain and diarrhoea, history of symptoms for < 3 months and low impairment of vitality at baseline were identified as positive predictors of outcome.

    Conclusions: Early response to treatment with a proton pump inhibitor, during the first week, seems to predict the outcome after 4 weeks in patients with functional dyspepsia.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2003
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13688 (URN)10.1046/j.1365-2036.2003.01651.x (DOI)
    Available from: 2003-06-15 Created: 2003-06-15 Last updated: 2018-05-23
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  • 182.
    Bolling-Sternevald, Elisabeth
    et al.
    Linköping University, Department of Biomedicine and Surgery.
    Carlsson, R.
    Aalykke, C.
    Wilson, BV.
    Ljunghard, O.
    AstraZeneca R&D, Mölndal, Sweden .
    Glise, Hans
    Linköping University, Department of Biomedicine and Surgery.
    Lauritsen, K.
    Department of Medical Gastroenterology, Odense University Hospital, Denmark.
    Self-administered symptom questionnaires in patients with dyspepsia and their yield in discriminating between endoscopic diagnoses2002In: Digestive diseases, Vol. 20, no 2, p. 191-198Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: Symptoms are generally considered to be poor predictors of organic findings in patients with dyspepsia. We aimed at evaluating whether specific gastrointestinal symptoms, identified by self-administered questionnaires, correlate with specific endoscopic diagnoses and discriminate organic from functional dyspepsia. METHODS: Adult patients with pain or discomfort centred in the upper abdominal region were consecutively enrolled. Patients with heartburn, acid regurgitation, or defaecation and bowel habit problems as their predominant symptoms were excluded. Three self-administered questionnaires were applied before an oesophagogastroduodenoscopy was performed. RESULTS: Among the 799 patients, 50.6% had a normal endoscopy. Endoscopic diagnoses comprised: non-erosive oesophagitis (7.5%), erosive oesophagitis (11.1%), Barrett's oesophagus (1.1%), gastritis/duodenitis (8.4%), gastric ulcer (4.5%), duodenal ulcer (8.3%), and cancer (1.3%). Non-dominant heartburn and acid regurgitation were significantly more common in patients with organic dyspepsia, whereas hunger pains and rumbling occurred more often in those with functional dyspepsia. Multivariate analyses demonstrated that younger age, female gender, high scores for hunger pain, rumbling, hard stools, low scores for heartburn, and acid regurgitation predicted functional dyspepsia. CONCLUSIONS: Self-administered questionnaires revealed differences in the symptom patterns between patients with functional and organic dyspepsia. Furthermore, the health-related well-being in patients with functional and organic dyspepsia centred was impaired to the same extent.

  • 183.
    Bolling-Sternevald, Elisabeth
    et al.
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Lauritsen, K.
    Department of Medical Gastroenterology, Odense University Hospital, Denmark.
    Melen, K.
    Carlsson, R.
    Jerndal, P.
    Ljunghard, O.
    AstraZeneca R&D, Mölndal, Sweden.
    Glise, Hans
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Aalykke, C.
    Havelund, T.
    Knudsen, T.
    Unge, Peter
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Ekstrom, P.
    Jaup, B.
    Norrby, A.
    Stubberod, A.
    Effect of Profound Acid Suppression in Functional Dyspepsia: a Double-Blind, Randomized, Placebo-Controlled Trial2002In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 37, no 12, p. 1395-1402Article in journal (Refereed)
    Abstract [en]

    Background: Functional dyspepsia (FD) is defined as persistent or recurrent pain/discomfort centred in the upper abdomen, where no structural explanation for the symptoms is found. The role of drug treatment remains controversial. The aim in this study was to evaluate the effect of omeprazole 20 mg twice daily (b.i.d) and to test methods for symptom assessment.

    Methods: 197 patients fulfilling the criteria for FD were randomly allocated to double-blind treatment with omeprazole 20 mg b.i.d ( n = 100) or placebo ( n = 97) for 14 days. Patients with a known gastrointestinal disorder or with main symptoms indicating gastro-oesophageal reflux disease or irritable bowel syndrome were excluded. Helicobacter pylori testing and 24-h intra-oesophageal 24-h pH-metry were performed before randomization. The patients recorded dyspeptic symptoms on diary cards.

    Results: A stringent endpoint, 'complete symptom relief on the last day of treatment', was the primary efficacy variable. For the APT cohort, this was achieved in 29.0% and 17.7% on omeprazole and placebo, respectively (95% CI of difference (11.3%): -0.4%-23.0%, P = 0.057). Similar figures in the PP cohort were 31.0% and 15.5%, respectively (95% CI of difference (15.5%): 3.2%-27.7%, P = 0.018). The benefit of omeprazole in the PP cohort was confirmed by secondary endpoints such as, no dyspeptic symptoms on the last 2 days of treatment and overall treatment response. H. pylori status and the level of oesophageal acid exposure did not significantly influence the response to therapy.

    Conclusion: A subset of patients with FD will respond to therapy with omeprazole.

  • 184.
    Bolling-Sternevald, Elisabeth
    et al.
    Linköping University, Department of Biomedicine and Surgery.
    Lauritsen, K.
    Department of Medical Gastroenterology, Odense University Hospital, Denmark.
    Talley, NJ.
    Department of Medicine, Nepean Hospital, Penrith, Australia.
    Ljunghard, O.
    AstraZeneca R&D, Mölndal, Sweden.
    Glise, Hans
    Linköping University, Department of Biomedicine and Surgery.
    Is it possible to predict treatment response to a proton pump inhibitor in functional dyspepsia?2003In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 18, no 1, p. 117-124Article in journal (Refereed)
    Abstract [en]

    Background: The efficacy of proton pump inhibitors in functional dyspepsia is modest and the prognostic factors are almost unknown.

    Methods: Data were pooled on patients (n = 826) with a diagnosis of functional dyspepsia from two placebo-controlled trials who were treated with omeprazole, 10 or 20 mg once daily, for 4 weeks. Self-administered questionnaires for the assessment of symptoms and health-related quality of life were completed before entry, and epigastric pain/discomfort was recorded on diary cards. Treatment success was defined as the complete absence of epigastric pain/discomfort on each of the last 3 days of week 4. Prognostic factors were identified by multiple logistic regression analysis.

    Results: The most discriminating predictor of treatment success (P < 0.0001) was the number of days with epigastric pain/discomfort during the first week of treatment. Fewer days with symptoms during the first week led to higher response rates at 4 weeks. In addition, age > 40 years, bothersome heartburn, low scores for bloating, epigastric pain and diarrhoea, history of symptoms for < 3 months and low impairment of vitality at baseline were identified as positive predictors of outcome.

    Conclusions: Early response to treatment with a proton pump inhibitor, during the first week, seems to predict the outcome after 4 weeks in patients with functional dyspepsia.

  • 185.
    Borch, Kurt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Ventrikelcancer - förändringar mot en bättre prognos.2000In: Incitament, ISSN 1103-503X, Vol. 7, p. 569-573Article in journal (Other (popular science, discussion, etc.))
  • 186.
    Borch, Kurt
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Ahrén, Bo
    Ahlman, Håkan
    Falkmer, Sture
    Granérus, Göran
    Grimelius, Lars
    Gastric carcinoids: Biologic behavior and prognosis after differentiated treatment in relation to type2005In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 242, no 1, p. 64-73Article in journal (Refereed)
    Abstract [en]

    Objective: To analyze tumor biology and the outcome of differentiated treatment in relation to tumor subtype in patients with gastric carcinoid. Background: Gastric carcinoids may be subdivided into ECL cell carcinoids (type 1 associated with atrophic gastritis, type 2 associated with gastrinoma, type 3 without predisposing conditions) and miscellaneous types (type 4). The biologic behavior and prognosis vary considerably in relation to type. Methods: A total of 65 patients from 24 hospitals (51 type 1, 1 type 2, 4 type 3, and 9 type 4) were included. Management recommendations were issued for newly diagnosed cases, that is, endoscopic or surgical treatment of type 1 and 2 carcinoids (including antrectomy to abolish hypergastrinemia) and radical resection for type 3 and 4 carcinoids. Results: Infiltration beyond the submucosa occurred in 9 of 51 type 1, 4 of 4 type 3, and 7 of 9 type 4 carcinoids. Metastases occurred in 4 of 51 type 1 (3 regional lymph nodes, 1 liver), the single type 2 (regional lymph nodes), 3 of 4 type 3 (all liver), and 7 of 9 type 4 carcinoids (all liver). Of the patients with type 1 carcinoid, 3 had no specific treatment, 40 were treated with endoscopic or surgical excision (in 10 cases combined with antrectomy), 7 underwent total gastrectomy, and 1 underwent proximal gastric resection. Radical tumor removal was not possible in 2 of 4 patients with type 3 and 7 of 9 patients with type 4 carcinoid. Five- and 10-year crude survival rates were 96.1% and 73.9% for type 1 (not different from the general population), but only 33.3% and 22.2% for type 4 carcinoids. Conclusion: Subtyping of gastric carcinoids is helpful in the prediction of malignant potential and long-term survival and is a guide to management. Long-term survival did not differ from that of the general population regarding type 1 carcinoids but was poor regarding type 4 carcinoids. Copyright © 2005 by Lippincott Williams & Wilkins.

  • 187.
    Borch, Kurt
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Grodzinsky, Ewa
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Petersson, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery.
    Jönsson, Kjell-Åke
    Mårdh, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Valdimarsson, Trausti
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology.
    Prevalence of coeliac disease and relations to Helicobacter pylori infection and duodenitis in a Swedish adult population sample: A histomorphological and serological survey2000In: InflammoPharmacology, ISSN 0925-4692, E-ISSN 1568-5608, Vol. 8, no 4, p. 341-350Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to determine the prevalence of coeliac disease and its relation to duodenitis, H. pylori infection and gastritis in a sample of the adult general population. Methods: A Swedish population sample of 482 subjects (aged 35 to 85 years) were examined with gastro-duodenoscopy with multiple biopsies taken. Circulating antibodies to endomycium, gliadin, and H. pylori were also determined. Results: Based on histomorphological findings, coeliac disease was evident in 9 of 482 subjects giving a prevalence of 1.9 [1.0-4.0, 95% confidence interval] percent. The prevalence of gastritis with or without H. pylori infection did not differ between subjects with and without coeliac disease. Considering subjects without coeliac disease, there was no difference in the serum levels of gliadin antibodies between those with and without duodenitis. However, subjects with positive H. pylori status had significantly higher levels of gliadin antibodies than those with negative H. pylori status. Conclusions: This study confirms that there is a relatively high prevalence of undiagnosed coeliac disease in Swedish adults. There was no association between coeliac disease and H. pylori infection or gastritis, although serum gliadin antibody levels were slightly increased in subjects with positive H. pylori status.

  • 188.
    Borch, Kurt
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Jönsson, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Vascular surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Tarpila, Erkki
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Franzén, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Berglund, J
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Vascular surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Kullman, Eric
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Franzén, L
    Changing pattern of histological type, location, stage and outcome of surgical treatment of gastric carcinoma2000In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 87, no 5, p. 618-626Article in journal (Refereed)
    Abstract [en]

    Background: There are indications that some features of gastric carcinoma are changing, with a possible impact on prognosis. The aim of this study was to examine any changes in type, location, stage, resection rate, postoperative mortality rate or prognosis for patients with gastric carcinoma in a well defined population. Methods: During 1974-1991, 1161 new cases of gastric adenocarcinoma were diagnosed in Ostergotland County, Sweden. Tumour location, Lauren histological type, tumour node metastasis (TNM) stage, radicality of tumour resection and postoperative complications were recorded after histological re-evaluation of tissue specimens and examination of all patient records. Dates of death were obtained from the Swedish Central Bureau of Statistics. Time trends were studied by comparing the intervals 1974-1982 (period 1) and 1983-1991 (period 2). Results: The proportion of diffuse type of adenocarcinoma increased (from 27 to 35 per cent), while that of mixed type decreased (from 16 to 9 per cent) and that of intestinal type was unchanged. The proportion of tumours located in the proximal two-thirds of the stomach increased (from 32 to 42 per cent) and the proportion of patients with tumours in TNM stage IV decreased (from 32 to 25 per cent). Overall tumour resection rates were unchanged, although the proportion of radical total gastrectomies increased (from 36 to 50 per cent). Excluding tumours of the cardia or gastric remnant after previous ulcer surgery, the 5-year relative survival rate after radical resection increased from 25 to 36 per cent and the postoperative mortality rate decreased for both radical (from 11 to 4 per cent) and palliative (from 18 to 6 per cent) resection. Conclusion: The patterns of tumour histology, location and stage of gastric carcinoma have changed in the authors' region. These changes were paralleled by a significant improvement in survival and postoperative mortality rates.

  • 189.
    Borch, Kurt
    et al.
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Jönsson, Kjell-Åke
    Petersson, Fredrik
    Redéen, Stefan
    Mårdh, Sven
    Franzén, Lennart
    Prevalence of gastroduodenitis and Helicobacter priori infection in a general population sample: relations to symptomatology and life-style2000In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 45, no 7, p. 1322-1329Article in journal (Refereed)
    Abstract [en]

    Some benign and malignant diseases develop on the background of chronic gastritis or duodenitis. The present study was performed in order to determine the magnitude of these background changes with relations to symptomatology and life style in the general population. Examinations were performed in 501 volunteers (age 35–85 years). Fifty percent had gastritis; this was associated with H. pylori in 87%. H. pylori-negative gastritis was associated with regular use of NSAIDs [odds ratio 3.8 (1.6–9.9)]. Duodenitis, observed in 32%, was associated with H. pylori infection [odds ratio 2.3 (1.3–4.6)], previous cholecystectomy [odds ratio 3.6 (1.1–16.1)], and regular use of NSAIDs [odds ratio 3.0 (1.4–7.1)]. Neither gastritis nor duodenitis was associated with smoking or alcohol consumption. The rate of digestive symptoms did not differ between subjects with and without uncomplicated gastritis or duodenitis. In conclusion, half of this adult population had gastritis strongly associated with H. pylori infection. Gastritis without H. pylori infection was frequently associated with regular NSAID intake. One third had duodenitis, which was associated with H. pylori infection as well as with regular use of NSAIDs and previous cholecystectomy. Digestive symptoms were not overrepresented in uncomplicated gastritis or duodenitis.

  • 190.
    Borch, Kurt
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, MKC-2, GE: Gastrokir.
    Petersson, Fredrik
    Kronisk gastrit - en asymptomatisk folksjukdom.2000In: Incitament, ISSN 1103-503X, Vol. 7, p. 558-562Article in journal (Other (popular science, discussion, etc.))
  • 191. Borg, H
    et al.
    Björk, E
    Bolinder, J
    Eriksson, JW
    Nyström, L
    Jeppsson, J-O
    Sundkvist, G
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-endo.
    Evaluation of the new ADA and WHO criteria for classification of diabetes mellitus in young adult people (15-34 yrs) in the Diabetes Incidence Study in Sweden (DISS)2003In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 46, no 2, p. 173-181Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis. We aimed to evaluate how an aetiology-based classification, as recommended in the ADA and WHO guidelines for classification of diabetes mellitus, matches clinical judgement in the Diabetes Incidence Study in Sweden (DISS), a study covering incident cases of diabetic patients aged 15 to 34 years. Methods. During a 1-year period (1998), blood samples were taken at diagnosis and 4 months (median) thereafter. Patients were classified according to clinical judgement by the reporting physicians and assessments of islet antibodies (ICA, GADA, and IA-2A) and plasma C-peptide. Results. In 1998, 422 patients were registered in DISS. Among the 313 patients participating in the follow-up, most with clinical Type 1 diabetes (185/218, 85%, 95% CI 79-89%) were islet antibody positive (ab+) at diagnosis. In addition, 14 out of 58 (24%, 14-37%) with clinical Type 2 diabetes and 21 out of 37 (57%, 40-73%) with unclassifiable diabetes were antibody positive at diagnosis. Further to this, 4 out of 33 (12%, 3-28%) were antibody negative with clinical Type 1 diabetes and 4 out of 44 (9%, 3-22%) with Type 2 had converted to antibody positive at follow-up. Among those who were constantly antibody negative, 10 out of 29 (34%, 18-54%) with clinical Type 1 and 1 out of 16 (6%, 0-30%) with unclassifiable diabetes had fasting plasma C-peptide concentrations below the normal range (<0.25 nmol/l) at follow-up. Conclusion/interpretation. Most young adults with clinical Type 1 diabetes (199/218, 91%) had objective Type 1 (ab+ at diagnosis/follow-up and/or low fasting plasma C-peptide concentrations at follow-up), as did one third (18/58, 31%) with clinical Type 2 diabetes and more than half (22/37, 59%) with unclassifiable diabetes. About 10% of those who were antibody negative converted to antibody positive. Our study underlines that a classification considering aetiology is superior to clinical judgement.

  • 192. Borisova, TK
    et al.
    Rosén, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Sidorova, EV
    Human monoclonal antibodies to synthetic viral peptides.1999In: Voprosy virusologii, ISSN 0507-4088, Vol. 44, p. 172-174Article in journal (Refereed)
  • 193.
    Boström, Sverre
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Bobinski, Lukas
    Zsigmond, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Nilsson, Inge
    Theodorsson, Annette
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    A new scaled microgauge for use in neurosurgery2005In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 147, no 12, p. 1281-1282Article in journal (Refereed)
    Abstract [en]

    A new scaled microgauge is described for measuring anatomical structures during microsurgery. The instrument has a tip marked in millimetres, which can be positioned in any desired angle enabling measurement in confined areas. © Springer-Verlag 2005.

  • 194.
    Bourghardt Peebo, Beatrice
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Gan, Lisha
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Knutsen Holmqvist, Annica
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Rearden, Ann
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Expression of the focal adhesion protein PINCH in normal and alkali-injured corneas and the role of PMNs2007In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 85, no 4, p. 395-400Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the role of particularly interesting new cysteine-histidine-rich protein (PINCH) in corneal wound healing and early neovascularization and to assess the influence of granulocytes. Methods: A standardized corneal alkali wound was inflicted under general anaesthesia to the right eye of 14 New Zealand White rabbits. Seven of the rabbits received i.v. 5 mg/kg fucoidin every 2 hours to prevent granulocytes from entering the wound area. After 36 hours, the rabbits were killed, the corneas excised, fixed in 4% formaldehyde and embedded in paraffin. The sections were double-stained with antibodies against PINCH and with haematoxylin. Results: In the normal cornea and limbus, PINCH was weakly expressed in the corneal epithelium and in a wedge of the conjunctival stroma. In the wounded corneas, PINCH expression was seen in the frontline of repopulating endothelial and epithelial cells, and in active keratocytes. The vascular endothelium and the granulocytes expressed PINCH, as did the conjunctival epithelium. In the fucoidin-treated rabbits, PINCH expression was markedly reduced. The vascular endothelial cells and the few granulocytes did not express PINCH in these rabbits. Conclusions: PINCH is only slightly expressed in the normal cornea. A corneal wound induces PINCH expression in the repopulating cells, in the vascular endothelial cells of the limbus, in the limbal epithelium and in the granulocytes. Exclusion of granulocytes reduces expression of PINCH and there is no expression at all in the vascular endothelium. © 2007 The Authors Journal compilation 2007 Acta Ophthalmol Scand.

  • 195. Boysen, Lene
    et al.
    Sörensen, Per
    Larsen, Morten
    Serup, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Kristensen, Flemming
    Evaluation of skin erythema by use of chromametry and image analysis of digital photographs after intradermal administration of histamine in dogs2002In: American Journal of Veterinary Research, ISSN 0002-9645, E-ISSN 1943-5681, Vol. 63, p. 565-569Article in journal (Refereed)
  • 196. Bracci-Laudiero, Luisa
    et al.
    Aloe, Luigi
    Buanne, Pasquale
    Finn, Anja
    Stenfors, Carina
    Vigneti, Eliana
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Lundeberg, Thomas
    NGF modulates CGRP synthesis in human B-lymphocytes: A possible anti-inflammatory action of NGF?2002In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 123, no 1-2, p. 58-65Article in journal (Refereed)
    Abstract [en]

    We investigated whether the sensory neuropeptide, calcitonin gene-related peptide (CGRP), could be synthesised by human lymphocytes. Our results indicate that in activated B-cells, there is a strong expression of CGRP gene transcripts, which is almost absent in resting cells. Since B-cells autocrinally produce NGF, the neutralisation of endogenous NGF by anti-NGF antibodies resulted in a marked reduction in CGRP expression in both resting and activated B-cells. Thus, NGF appears to directly affect the synthesis of CGRP in B-cells as in sensory neurons. By regulating CGRP synthesis in lymphocytes and neuronal cells, NGF can influence the intensity and duration of the immune response. ⌐ 2002 Elsevier Science B.V. All rights reserved.

  • 197. Bracci-Laudiero, Luisa
    et al.
    Aloe, Luigi
    Lundeberg, Thomas
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Stenfors, Carina
    Altered levels of neuropeptides characterize the brain of lupus prone mice.1999In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 273Article in journal (Refereed)
  • 198. Brenne, Anne-Tove
    et al.
    Hejna Romstad, Lene
    Gimsing, Peter
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Turesson, Ingemar
    Romundstad, Pål
    Borset, Magne
    Sundan, Anders
    Waage, Anders
    A low serum level of soluble tumor necrosis factor receptor p55 predicts response to thalidomide in advanced multiple myeloma2004In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 89, no 5, p. 552-556Article in journal (Refereed)
    Abstract [en]

    Background and Objectives. Thalidomide modulates the production of tumor necrosis factor (TNF-α). Soluble TNF receptors, TNFR p55 and TNFR p75, modify TNF-α activity. In this study, we explored the relation between soluble TNF receptors and outcome in patients with advanced multiple myeloma treated with thalidomide. Design and Methods. The levels of soluble TNF receptor p55 and p75 were assessed in serum from 34 myeloma patients with relapsed or refractory disease before starting thalidomide treatment. Serial measurements were performed for 16 patients in serum collected during treatment. Results. The pre-treatment serum level of soluble TNFR p55 in thalidomide responders was significantly lower than that in non-responders (median 1.75 ng/mL (range 1.19-2.84) vs. 2.79 ng/mL (1.36-5.51), p=0.004). The levels of p55 declined significantly during treatment. The levels of p75 showed the same pattern as p55, but the differences were not significant. The median survival of myeloma patients with pre-treatment levels of p55 < 2.79 ng/mL was 404 days, the median survival of patients with pre-treatment levels ≥ 2.79 ng/mL was shorter (65 days, log-rank test p=0.02). Interpretation and Conclusions. We conclude that soluble TNFR p55 is an adverse prognostic factor in myeloma patients with relapsed or refractory disease treated with thalidomide. Patients with a low pre-treatment level of this receptor have a better response rate and a longer overall survival.

  • 199.
    Brodin Patcha, Veronika
    et al.
    Linköping University, Department of Biomedicine and Surgery.
    Särndahl, Eva
    Inside-out regulated β2-integrin-induced release of arachidonic acid in Human Leukemia 60 cellsManuscript (Other academic)
  • 200.
    Brodin Patcha, Veronika
    et al.
    Linköping University, Department of Biomedicine and Surgery.
    Särndahl, Eva
    LIpoxin A4 inhibits the fMet-Leu-Phe-induced, but not the β2 integrin-induced activation of the non-receptor tyrosine kinase Pyk2 in Human Leukemia 60 cellsManuscript (Other academic)
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