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  • 201.
    Markström, Agneta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Hedlund, Anders
    Lichtwarck-Aschoff, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nordgren, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjöstrand, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Impact of different inspiratory flow patterns on arterial C02-tension2000In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 105, no 1, p. 17-29Article in journal (Refereed)
    Abstract [en]

    Ventilation with decelerating inspiratory flow is known to reduce the dead space fraction and to decrease PaCO2. Constant inspiratory flow with an end-inspiratory pause (EIP) is also known to increase the removal of CO2. The aim of the study was to elucidate the effect of the pause/no-flow period while both the pattern and rate of inspiratory flow was unchanged, and when the lung was ventilated with sufficient PEEP to prevent end-expiratory collapse. Surfactant depleted piglets were assigned to decelerating or constant inspiratory flow with 24 breaths per minute (bpm) or 12 bpm, or to constant flow, without and with an end-inspiratory pause of 25%. By adding an EIP the total time without active inspiratory flow of the respiratory cycle was kept unchanged. Gas exchange, airway pressures, functional residual capacity (using sulfurhexafluoride) and haemodynamics (thermo-dye indicator dilution technique) were measured. Irrespective of ventilatory frequency, PaCO2 was lower and serial dead space reduced with decelerating flow, compared with constant inspiratory flow. With an end-inspiratory pause added to constant inspiratory flow, serial dead space was reduced but did not decrease PaCO2. The results of this study corroborate the assumption that total time without active inspiratory flow is important for arterial CO2-tension.

  • 202.
    Marsell, Richard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Successful treatment of a humeral capitulum osteonecrosis with bone morphogenetic protein-7 combined with autologous bone grafting2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 3, p. 287-289Article in journal (Refereed)
    Abstract [en]

    We present the case of a 27-year-old female with subcortical osteonecrosis of the humeral capitulum. Percutaneous retrograde drilling of the lesion and application of recombinant human bone morphogenetic protein (BMP)-7 were combined with autologous bone grafting. At follow-up the patient was almost pain-free, had normalized her range of motion, and radiography showed consolidation of the lesion without any heterotopic bone formation. By timing surgery prior to subchondral collapse, biomechanical stability of the subchondral bone was maintained. To our knowledge, this is the first report on the treatment of an osteonecrosis in this location with a BMP, and this strategy could potentially be applied in other locations with juxta-articular osteonecrosis.

  • 203.
    Martinell, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Hallqvist, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Automated data extraction: A feasible way to construct patient registers of primary care utilization2012In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 1, p. 52-56Article in journal (Refereed)
    Abstract [en]

    Introduction. Electronic medical records (EMRs) enable analysis of health care data by using data mining techniques to build research databases. Though the reliability of the data extraction process is crucial for the credibility of the final analysis, there are few published validations of this process. In this paper we validate the performance of an automated data mining tool on EMR in a primary care setting.

    Methods. The Pygargus Customized eXtraction Program (CXP) was programmed to find and then extract data from patients meeting criteria for type 2 diabetes mellitus (T2DM) at one primary health care clinic (PHC). The ability of CXP to extract relevant cases was assessed by comparing cases extracted by an EMR integrated search engine. The concordance of extracted data with the original EMR source was manually controlled.

    Results. Prevalence of T2DM was 4.0%, which correspond well to previous estimations. By searching for drug prescriptions, diagnosis codes, and laboratory values, 38%, 53%, and 91% of relevant cases were found, respectively. The sensitivity of CXP regarding extraction of relevant cases was 100%. The specificity was 99.9% due to 12 non-T2DM cases extracted. The congruity at single-item level was 99.6%. The 13 incorrect data items were all located in the same structural module.

    Conclusion. The CXP is a reliable and accurate data mining tool to extract selective data from EMR.

  • 204.
    Mattebo, Magdalena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research. Mälardalen Univ, Sch Hlth Care & Social Welf, Västerås, Sweden.
    Tydén, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Häggström-Nordin, Elisabet
    Mälardalen Univ, Sch Hlth Care & Social Welf, Västerås, Sweden.
    Nilsson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Larsson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Pornography consumption and psychosomatic and depressive symptoms among Swedish adolescents: a longitudinal study2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 4, p. 237-246Article in journal (Refereed)
    Abstract [en]

    Background: The aims of this longitudinal study were to identify predictors for continued pornography consumption and to investigate pornography consumption in relation to psychosomatic and depressive symptoms among a group of adolescents in Sweden.

    Methods and materials: A longitudinal study in classroom environment in 53 randomly selected senior high school classes in mid-Sweden in years 2011 and 2013. Out of 477 participating boys and 400 girls in 2011, 224 boys (47%) and 238 girls (60%) participated in 2013.

    Results: Higher pornography consumption at baseline and being born outside Sweden predicted continued pornography consumption at follow-up (adjusted R2 = 0.689).

    Psychosomatic symptoms at follow-up were predicted by higher pornography consumption at baseline (adjusted R2 = 0.254), being a girl, living with separated parents, and attending a vocational high school program. By contrast, depressive symptoms at follow-up were predicted by less pornography consumption at baseline (adjusted R2 = 0.122) and being a girl.

    Conclusions: Pornography consumption may, for some individuals, be associated to mental health issues. Differences between teenage boys and girls and between adolescents with diverse ethnic backgrounds imply that counseling and discussion about pornography need to be adjusted and individualized.

  • 205.
    Mei, Xueshuang
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Peking Univ, Shenzhen Hosp, Dept Otolaryngol, Beijing, Peoples R China.
    Atturo, Francesca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Wadin, Karin
    Uppsala Univ Hosp, Dept Diagnost Radiol, Uppsala, Sweden.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Agrawal, Sumit
    Western Univ, Dept Otolaryngol Head & Neck Surg, London, ON, Canada.
    Ladak, Hanif M.
    Western Univ, Dept Otolaryngol Head & Neck Surg, London, ON, Canada;Western Univ, Dept Med Biophys, London, ON, Canada;Western Univ, Dept Elect & Comp Engn, London, ON, Canada.
    Li, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Human inner ear blood supply revisited: the Uppsala collection of temporal bone - an international resource of education and collaboration2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 3, p. 131-142Article in journal (Refereed)
    Abstract [en]

    Background: The Uppsala collection of human temporal bones and molds is a unique resource for education and international research collaboration. Micro-computerized tomography (micro-CT) and synchrotron imaging are used to investigate the complex anatomy of the inner ear. Impaired microcirculation is etiologically linked to various inner ear disorders, and recent developments in inner ear surgery promote examination of the vascular system. Here, for the first time, we present three-dimensional (3D) data from investigations of the major vascular pathways and corresponding bone channels.

    Methods: We used the archival Uppsala collection of temporal bones and molds consisting of 324 inner ear casts and 113 macerated temporal bones. Micro-CT was used to investigate vascular bone channels, and 26 fresh human temporal bones underwent synchrotron radiation phase contrast imaging (SR-PCI). Data were processed by volume-rendering software to create 3D reconstructions allowing orthogonal sectioning, cropping, and soft tissue analyses.

    Results: Micro-CT with 3D rendering was superior in reproducing the anatomy of the vascular bone channels, while SR-PCI replicated soft tissues. Arterial bone channels were traced from scala vestibuli (SV) arterioles to the fundus, cochlea, and vestibular apparatus. Drainage routes along the aqueducts were examined.

    Conclusion: Human inner ear vessels are difficult to study due to the adjoining hard bone. Micro-CT and SR-PCI with 3D reconstructions revealed large portions of the micro-vascular system in un-decalcified specimens. The results increase our understanding of the organization of the vascular system in humans and how altered microcirculation may relate to inner ear disorders. The findings may also have surgical implications.

  • 206.
    Mindemark, Mirja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Longitudinal trends in laboratory test utilization at a large tertiary care university hospital in Sweden2011In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 116, no 1, p. 34-38Article in journal (Refereed)
    Abstract [en]

    Background. The aim of the study was to describe and evaluate longitudinal trends in laboratory test utilization over a 7-year period from 2002 to 2008. Method. Retrospective study using test request data from the Clinical Chemistry and Pharmacology Laboratory at Akademiska Sjukhuset, a large tertiary care university hospital in Sweden. Changes in test utilization, charges, and expenditures during the study period were used as main outcome measures. Results. Laboratory test utilization increased by over 70%, with a mean annual increase of 9.3% during the study period. After adjustment for inflation, the laboratory expenditures increased by 20.2% during the study period but represented only approximately 2.0% of the hospital's total expenditure in 2008. The test menu comprised 663 tests in 2008, an increase by 146% from 2002. The mean inflation-adjusted unit price charged per test increased from €34.9 to €37.5 during the study period. The top 10, 20, and 30 tests accounted for, on average, 46.9%, 66.9%, and 75.5% of the total test volume during the study period, and 47.8%, 66.4%, and 75.7% of the total test volume in 2008. In 2008, 10 analyses, i.e. 1.5% of the number of tests on the menu, accounted for almost half the number of generated test results. Conclusions. The total number of generated test results increased by over 70% in less than a decade. Even so, the laboratory's share of the hospital's total expenditure remained low and virtually unchanged. A very small number of tests accounted for a disproportionately large share of the total number of generated test results.

     

  • 207.
    Miyazono, Kohei
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
    Ehata, Shogo
    Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
    Koinuma, Daizo
    Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
    Tumor-promoting functions of transforming growth factor-β in progression of cancer2012In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 2, p. 143-152Article, review/survey (Refereed)
    Abstract [en]

    Transforming growth factor-β (TGF-β) elicits both tumor-suppressive and tumor-promoting functions during cancer progression. Here, we describe the tumor-promoting functions of TGF-β and how these functions play a role in cancer progression. Normal epithelial cells undergo epithelial-mesenchymal transition (EMT) through the action of TGF-β, while treatment with TGF-β and fibroblast growth factor (FGF)-2 results in transdifferentiation into activated fibroblastic cells that are highly migratory, thereby facilitating cancer invasion and metastasis. TGF-β also induces EMT in tumor cells, which can be regulated by oncogenic and anti-oncogenic signals. In addition to EMT promotion, invasion and metastasis of cancer are facilitated by TGF-β through other mechanisms, such as regulation of cell survival, angiogenesis, and vascular integrity, and interaction with the tumor microenvironment. TGF-β also plays a critical role in regulating the cancer-initiating properties of certain types of cells, including glioma-initiating cells. These findings thus may be useful for establishing treatment strategies for advanced cancer by inhibiting TGF-β signaling.

  • 208.
    Mohlin, Camilla
    et al.
    Linnaeus Univ, Linnaeus Ctr Biomat Chem, Fac Hlth & Life Sci, Kalmar, Sweden.
    Sandholm, Kerstin
    Linnaeus Univ, Linnaeus Ctr Biomat Chem, Fac Hlth & Life Sci, Kalmar, Sweden.
    Kvanta, Anders
    Karolinska Inst, St Erik Eye Hosp, Sect Ophthalmol & Vis, Dept Clin Neurosci, Stockholm, Sweden.
    Nilsson Ekdahl, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Univ, Linnaeus Ctr Biomat Chem, Fac Hlth & Life Sci, Kalmar, Sweden.
    Johansson, Kjell
    Orebro Univ, Sch Med Sci, Orebro, Sweden.
    A model to study complement involvement in experimental retinal degeneration2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 1, p. 28-42Article in journal (Refereed)
    Abstract [en]

    Background: The complement system (CS) plays a role in the pathogenesis of a number of ocular diseases, including diabetic retinopathy (DR), glaucoma, uveitis, and age-related macular degeneration (AMD). Given that many of the complex eye-related degenerative diseases have limited treatment opportunities, we aimed to mimic the in vivo retinal degenerative process by developing a relevant co-culture system.

    Method and materials: The adult porcine retina was co-cultured with the spontaneously arising human retinal pigment epithelial cells-19 (ARPE-19).

    Results: Inflammatory activity was found after culture and included migrating microglial cells, gliosis, cell death, and CS activation (demonstrated by a minor increase in the secreted anaphylotoxin C3a in co-culture). CS components, including C1q, C3, C4, soluble C5b-9, and the C5a receptor, were expressed in the retina and/or ARPE cells after culture. C1q, C3, and CS regulators such as C4 binding protein (C4BP), factor H (CFH), and factor I (CFI) were secreted after culture.

    Discussion: Thus, our research indicates that this co-culturing system may be useful for investigations of the CS and its involvement in experimental neurodegenerative diseases.

  • 209.
    Molnar, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lennmyr, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Neuroprotection by S-PBN in hyperglycemic ischemic brain injury in rats2010In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 115, no 3, p. 163-168Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hyperglycemia exacerbates focal ischemic brain damage supposedly through various mechanisms. One such mechanism is oxidative stress involving reactive oxygen and nitrogen species (RONS) production. Nitrones attenuate oxidative stress in various models of brain injury. Sodium 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) can be administered experimentally and has been shown to be neuroprotective in experimental brain trauma. AIMS OF THE STUDY: We hypothesized that S-PBN might be neuroprotective in hyperglycemic focal cerebral ischemia. MATERIAL AND METHODS: Rats were made hyperglycemic by an intraperitoneal bolus injection of glucose (2 g/kg) and then subjected to 90 min transient middle cerebral artery occlusion (MCAO). They were randomized to a therapeutic regime of S-PBN (156 mg/kg) or saline given intravenously. Neurological testing according to Bederson and tetrazolium red staining were performed after 1 day. RESULTS: S-PBN improved the neurological performance at day 1 both in Bederson score (1.3+/-0.8 versus 2.7+/-0.48) and on the inclined plane (74.5%+/-4.6 (S-PBN) versus 66%+/-8.3 (control), P<0.05) but did not reduce the infarct size. Physiological data did not differ between groups. CONCLUSION: S-PBN may improve neurological performance at short-term survival (1 day) in the present model of hyperglycemic-ischemic brain injury in rats. This effect appeared not to be primarily related to reduced infarct size.

  • 210.
    Mosavi, Firas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ullenhag, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Whole-body MRI including diffusion-weighted imaging compared to CT for staging of malignant melanoma2013In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 2, p. 91-97Article in journal (Refereed)
    Abstract [en]

    Background. Whole-body (WB) magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), has been increasingly used for the detection of metastatic disease. Purpose. To assess the value of WB MRI including DWI compared to computed tomography (CT) for staging of malignant melanoma. A second aim was to assess the value of DWI in addition to conventional MR sequences for the detection of lesions. Material and methods. WB MRI with DWI and CT chest, abdomen, and pelvis were performed in 23 patients with histologically confirmed malignant melanoma. CT before and after the MRI examinations and the clinical follow-up was utilized as the standard of reference. Results. WB MRI and WB DWI detected 345 and 302 lesions, respectively, compared to 397 lesions with CT. The sensitivity of WB MRI and WB DWI varied considerably in different regions of the body. In the lungs, WB MRI and WB DWI showed 63% and 47% true-positive lesions, respectively. WB MRI and WB DWI detected 56 bone lesions in 12 patients compared to 42 lesions in 8 patients with CT. In addition, WB MRI and WB DWI could detect 68 lesions outside the field of view of CT in six patients. Conclusion. WB MRI is still not ready to replace CT for staging of malignant melanoma, especially in the thorax region. However, WB MRI is advantageous for detection of bone lesions and lesions outside the investigated volume of the conventional CT. When WB MRI is evaluated, both DWI and conventional MRI sequences must be scrutinized.

  • 211.
    Mutschler, Diana K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Gustafsson, Urban
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Larsson, Anders O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Eriksson, Mats B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Ropivacaine may have advantages compared to bupivacaine in porcine endotoxemic shock2006In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 111, no 2, p. 189-199Article in journal (Refereed)
    Abstract [en]

    Patients that undergo major abdominal surgery often receive epidural postoperative analgesia. Septic complications are frequently seen in this cohort. In a porcine model of endotoxemic shock, resembling human gram-negative septic shock, we evaluated the effects of two widely used local anaesthetics, bupivacaine and ropivacaine given intravenously. In the endotoxin-ropivacaine group mixed venous saturation and platelet count were higher as compared to endotoxemic controls. Mean arterial blood pressure and platelet count were higher in ropivacaine-endotoxin pigs than in bupivacaine-endotoxin ones. Bupivacaine augmented endotoxin-mediated decrease in left ventricular stroke work index. Ropivacaine displays pathophysiological advantages compared to bupivacaine in septic shock, which may be explained by improved tissue perfusion by ropivacaine.

  • 212.
    Målqvist, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH). Uppsala Univ, Dept Womens & Childrens Hlth, Int Maternal & Child Hlth, Uppsala, Sweden.
    Community agency and empowerment: a need for new perspectives and deepened understanding2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 2, p. 123-130Article in journal (Refereed)
    Abstract [en]

    Background: In an increasingly globalized and interlinked world it becomes ever more important to find strategies to prevent, detect, and respond to emerging public health threats. Local communities have a central role in this effort and need to be empowered and strengthened to be able to meet the challenge, and local knowledge and participation are key. This paper outlines a theoretical framework for community intervention dynamics and explores perceptions, priorities, and perspectives of stakeholders involved in community interventions. Methods: A deductive discourse analysis was performed based on the proposed theoretical framework consisting of three levels: intervention design, intervention delivery, and community agency. The setting was a workshop on community preparedness at Uppsala Health Summit 2017. Thirty-eight participants representing government officials, international organizations, and researchers as well as community implementers underwent a value exercise and were asked to prioritize good practices, challenges, and needed solutions to empower communities to meet emerging health threats. Results: The value exercise revealed a large variation in basic values among participants. Discussions mainly focused on intervention delivery and choice of methods. Need and allocation of resources at any level was not an issue. Despite being probed to take a deeper look at contextual factors and the underlying drivers of community engagement, participants scarcely mentioned and problematized community agency mechanisms. Conclusion: There is a need for new perspectives and a deepened reflection among decision-makers and public health implementers engaging at the local level to strengthen communities to face public health threats. A greater understanding and focus on contextual factors is needed which necessitates stronger interdisciplinary approaches.

  • 213. Nilsson, B O
    et al.
    Hjortberg, M
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sjögren, A
    Hamberger, L
    Monoclonal antibodies against human blastocysts.1995In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 100, no 3Article in journal (Refereed)
    Abstract [en]

    A panel of monoclonal antibodies against the implanting mouse blastocyst was tested for cross-reactivity to human blastocysts. The monoclonal antibodies were produced by intrasplenic immunization with living mouse blastocysts or egg-cylinders. Among the 13 anti-mouse blastocyst antibodies checked, 6 ones detected antigen epitopes also in human blastocysts. If the mouse-human cross-reacting antibodies detect similar antigens in blastocysts of the two species, the results imply that anti-mouse blastocyst antibodies with specific properties could be used for studying human blastocysts. This procedure opens for a way to obtain monoclonal antibodies for analysing human blastocysts.

  • 214.
    Nilsson, Kent W
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Kronstrand, Robert
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Smoking as a product of gene-environment interaction2009In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 114, no 2, p. 100-107Article in journal (Refereed)
    Abstract [en]

    A strong hereditary influence on smoking has been demonstrated. As one of the candidate genes in relation to smoking, the serotonin transporter gene (5-HTTLPR) has been suggested, however with conflicting results. In recent studies, it has been shown that genotypic and environmental (G*E) factors interact in the shaping of a variety of phenotypic expressions. The objective of the present study was to investigate the interaction between a variation in the 5-HTTLPR and family environment in relation to smoking habits, nicotine dependence, and nicotine and cotinine levels in hair samples. A random Swedish adolescent population sample (n = 785), from which 200 individuals were stratified regarding behaviour, was genotyped for 5-HTTLPR and assessed with semi-structured interviews, a questionnaire, and hair analyses of nicotine and cotinine. The 5-HTTLPR gene interacted with a poor family environment to predict smoking habits, as well as nicotine and cotinine levels. The risk of being a smoker was increased 13 times for an individual with a combination of the 5-HTTLPR LS genotype and a poor family environment in comparison with the Homozygous Long-Long (LL) genotype and a good family environment.

  • 215.
    Nilsson, Sven
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nilsson, Folke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Calcified leiomyosarcoma simulating uterine myoma in a patient with long-standing anaemia1991In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 96, no 2, p. 141-147Article in journal (Refereed)
    Abstract [en]

    A case of small bowel leiomyosarcoma in a 75-year-old woman is reviewed. The patient had an unexplained anaemia with occult blood in the faeces for at least 15 years. The value of different radiological investigations in patients with suspected gastrointestinal bleeding is discussed. The possible significance of calcifications visible on plain abdominal films is emphasized.

  • 216.
    Nordenankar, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Neurobiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Bergfors, Assar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Neurobiology.
    Wallén-Mackenzie, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Neurobiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Targeted deletion of Vglut2 expression in the embryonal telencephalon promotes an anxiolytic phenotype of the adult mouse2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 3Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Anxiety is a natural emotion experienced by all individuals. However, when anxiety becomes excessive, it contributes to the substantial group of anxiety disorders that affect one in three people and thus are among the most common psychiatric disorders. Anxiolysis, the reduction of anxiety, is mediated via several large groups of therapeutical compounds, but the relief is often only temporary, and increased knowledge of the neurobiology underlying anxiety is needed in order to improve future therapies.

    AIM: We previously demonstrated that mice lacking forebrain expression of the Vesicular glutamate transporter 2 (Vglut2) from adolescence showed a strong anxiolytic behaviour as adults. In the current study, we wished to analyse if removal of Vglut2 expression already from mid-gestation of the mouse embryo would give rise to similar anxiolysis in the adult mouse.

    METHODS: We produced transgenic mice lacking Vglut2 from mid-gestation and analysed their affective behaviour, including anxiety, when they had reached adulthood.

    RESULTS: The transgenic mice lacking Vglut2 expression from mid-gestation showed certain signs of anxiolytic behaviour, but this phenotype was not as prominent as when Vglut2 was removed during adolescence.

    CONCLUSION: Our results suggest that both embryonal and adolescent forebrain expression of Vglut2 normally contributes to balancing the level of anxiety. As the neurobiological basis for anxiety is similar across species, our results in mice may help improve the current understanding of the neurocircuitry of anxiety, and hence anxiolysis, also in humans.

  • 217.
    Nordquist, Niklas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Serotonin, genetic variability, behaviour, and psychiatric disorders: a review2010In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 115, no 1, p. 2-10Article, review/survey (Refereed)
    Abstract [en]

    Brain monoamines, and serotonin in particular, have repeatedly been shown to be linked to different psychiatric conditions such as depression, anxiety, antisocial behaviour, and dependence. Many studies have implicated genetic variability in the genes encoding monoamine oxidase A (MAOA) and the serotonin transporter (5HTT) in modulating susceptibility to these conditions. Paradoxically, the risk variants of these genes have been shown, in vitro, to increase levels of serotonin, although many of the conditions are associated with decreased levels of serotonin. Furthermore, in adult humans, and monkeys with orthologous genetic polymorphisms, there is no observable correlation between these functional genetic variants and the amount or activity of the corresponding proteins in the brain. These seemingly contradictory data might be explained if the association between serotonin and these behavioural and psychiatric conditions were mainly a consequence of events taking place during foetal and neonatal brain development. In this review we explore, based on recent research, the hypothesis that the dual role of serotonin as a neurotransmitter and a neurotrophic factor has a significant impact on behaviour and risk for neuropsychiatric disorders through altered development of limbic neurocircuitry involved in emotional processing, and development of the serotonergic neurons, during early brain development.

  • 218.
    Nyberg, Karl
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hedman, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Swedish guidelines for registry-based randomized clinical trials2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 33-36Article in journal (Refereed)
    Abstract [en]

    During the last decade Sweden has invested in a national infrastructure for collection of structured clinical data in the form of healthcare registries (in Sweden known as Kvalitetsregister). These data can be combined with other public data using the national personal identifiers that are issued to Swedish citizens. The healthcare registries have an almost complete coverage of Swedish healthcare, and a large network of clinicians is involved in the quality assurance and continuous improvement of healthcare using these registries. Uppsala Clinical Research Center (UCR) has been a technology provider of large-scale national registries and has a strong background in clinical trial management. This effort combines the areas of healthcare registries and clinical trials into a novel way of performing clinical trials to be able to: 1) run clinical trials as an integrated part of normal clinic workflow; and 2) leverage the nationwide network of outcome reporting. This strategy was shown to be successful in the TASTE (Thrombus Aspiration in Myocardial Infarction) study. When TASTE had been published, the New England Journal of Medicine wrote a perspective on the study calling it 'The randomized registry trial-the next disruptive technology in clinical research?' Since then several studies have been conducted in this way with great success. UCR has been appointed, by Clinical Studies Sweden and the Swedish Research Council, to develop the Swedish national guidelines for registry-based randomized clinical trials in order to ensure the possibility for more organizations to run this kind of study. This paper describes key concepts of register-based randomized clinical trials and the development of Swedish national guidelines.

  • 219.
    Nyholm, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Introduction of the Uppsala Traumatic Brain Injury register for regular surveillance of patient characteristics and neurointensive care management including secondary insult quantification and clinical outcome2013In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 3, p. 169-180Article in journal (Refereed)
    Abstract [en]

    Background. To improve neurointensive care (NIC) and outcome for traumatic brain injury (TBI) patients it is crucial to define and monitor indexes of the quality of patient care. With this purpose we established the web-based Uppsala TBI register in 2008. In this study we will describe and analyze the data collected during the first three years of this project. Methods. Data from the medical charts were organized in three columns containing: 1) Admission data; 2) Data from the NIC period including neurosurgery, type of monitoring, treatment, complications, neurological condition at discharge, and the amount of secondary insults; 3) Outcome six months after injury. Indexes of the quality of care implemented include: 1) Index of improvement; 2) Index of change; 3) The percentages of 'Talk and die' and `Talk and deteriorate' patients. Results. Altogether 314 patients were included 2008-2010: 66 women and 248 men aged 0-86 years. Automatic reports showed that the proportion of patients improving during NIC varied between 80% and 60%. The percentage of deteriorated patients was less than 10%. The percentage of Talk and die/Talk and deteriorate cases was <1%. The mean Glasgow Coma Score (Motor) improved from 5.04 to 5.68 during the NIC unit stay. The occurrences of secondary insults were less than 5% of good monitoring time for intracranial pressure (ICP) >25 mmHg, cerebral perfusion pressure (CPP) <50 mmHg, and systolic blood pressure <100 mmHg. Favorable outcome was achieved by 64% of adults. Conclusion. The Uppsala TBI register enables the routine monitoring of NIC quality indexes.

  • 220.
    Nyholm, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Howells, Timothy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    The influence of hyperthermia on intracranial pressure, cerebral oximetry and cerebral metabolism in traumatic brain injury2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 3, p. 177-184Article in journal (Refereed)
    Abstract [en]

    Background: Hyperthermia is a common secondary insult in traumatic brain injury (TBI). The aim was to evaluate the relationship between hyperthermia and intracranial pressure (ICP), and if intracranial compliance and cerebral blood flow (CBF) pressure autoregulation affected that relationship. The relationships between hyperthermia and cerebral oximetry (B(ti)pO(2)) and cerebral metabolism were also studied. Methods: A computerized multimodality monitoring system was used for data collection at the neurointensive care unit. Demographic and monitoring data (temperature, ICP, blood pressure, microdialysis, B(ti)pO(2)) were analyzed from 87 consecutive TBI patients. ICP amplitude was used as measure of compliance, and CBF pressure autoregulation status was calculated using collected blood pressure and ICP values. Mixed models and comparison between groups were used. Results: The influence of hyperthermia on intracranial dynamics (ICP, brain energy metabolism, and B(ti)pO(2)) was small, but individual differences were seen. Linear mixed models showed that hyperthermia raises ICP slightly more when temperature increases in the groups with low compliance and impaired CBF pressure autoregulation. There was also a tendency (not statistically significant) for increased B(ti)pO(2), and for increased pyruvate and lactate, with higher temperature, while the lactate/pyruvate ratio and glucose were stable. Conclusions: The major finding was that the effects of hyperthermia on intracranial dynamics (ICP, brain energy metabolism, and B(ti)pO(2)) were not extensive in general, but there were exceptional cases. Hyperthermia treatment has many side effects, so it is desirable to identify cases in which hyperthermia is dangerous. Information from multimodality monitoring may be used to guide treatment in individual patients.

  • 221.
    Ochala, Julien
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Carpén, Olli
    Larsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Maintenance of muscle mass, fiber size, and contractile function in mice lacking the Z-disc protein myotilin2009In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 114, no 4, p. 235-241Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Myofibrillar myopathies constitute a rare group of congenital neuromuscular disorders, frequently associated with mutations in Z-disc proteins such as myotilin. Myotilin location and interactions with other Z-disc proteins are clearly defined, but its role in the regulation of muscle structure and function remains unknown. The present study aims at investigating this specific role of myotilin. METHODS: Skeletal and cardiac muscles were collected from adult mice with a targeted deletion of myotilin (myo(-/-)) and wild-type animals (myo(+/+)). RESULTS AND CONCLUSION: Similar skeletal and cardiac muscle weights were observed in myo(-/-) and myo(+/+) mice. At the muscle cell level, the size and force production of single membrane permeabilized fibers were identical between myo(-/-) and myo(+/+) rodents. Thus, myotilin does not have a significant influence on muscle mass, muscle fiber size, or regulation of muscle contraction. Alternatively, compensatory over-expressions of other elements including proteins from the same subfamily, or Z-disc proteins such as telethonin, or intermediate filaments may compensate for the lack of myotilin.

  • 222.
    Olai, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Borgquist, Lars
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Health problems in elderly patients during the first post-stroke year2012In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 3, p. 318-327Article in journal (Refereed)
    Abstract [en]

    Background. A wide range of health problems has been reported in elderly post-stroke patients. Aim. The aim of this study was to analyse the prevalence and timing of health problems identified by patient interviews and scrutiny of primary health care and municipality elderly health care records during the first post-stroke year.

    Methods. A total of 390 consecutive patients, >= 65 years, discharged alive from hospital after a stroke event, were followed for 1 year post-admission. Information on the health care situation during the first post-stroke year was obtained from primary health care and municipal elderly health care records and through interviews with the stroke survivors, at 1 week after discharge, and 3 and 12 months after hospital admission.

    Results. More than 90% had some health problem at some time during the year, while based on patient record data only 4-8% had problems during a given week. The prevalence of interview-based health problems was generally higher than record-based prevalence, and the ranking order was moderately different. The most frequently interview-reported problems were associated with perception, activity, and tiredness, while the most common record-based findings indicated pain, bladder and bowel function, and breathing and circulation problems. There was co-occurrence between some problems, such as those relating to cognition, activity, and tiredness.

    Conclusions. Almost all patients had a health problem during the year, but few occurred in a given week. Cognitive and communication problems were more common in interview data than record data. Co-occurrence may be used to identify subtle health problems.

  • 223.
    Olai, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Borgquist, Lars
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Life situations and the care burden for stroke patients and their informal caregivers in a prospective cohort study2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 4, p. 290-298Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The purpose of this study was to analyse whether the parallel life situation between stroke patients and their informal caregivers (dyads) shown in cross-sectional studies prevails also in a longitudinal perspective.

    METHODS: A total of 377 Swedish stroke patients, aged ≥65 years, and their 268 informal caregivers were followed from hospital admission and one year on. Analyses were based on patient interviews, functional ability (MMSE) score, Nottingham Health Profile (NHP) score, Hospital Anxiety and Depression (HAD) score, self-rated health score, and the Gothenburg Quality of Life (GQL) activity score. Similar information was obtained by postal questionnaires from informal caregivers, also including information on the nature and amount of assistance provided and on Caregiver Burden (CB) score.

    RESULTS: Before index admission informal caregivers provided care on average 5 h per week and after discharge 11 h per week (P < 0.0001). Support volume was associated with patient sex (more for men), low patient's functional ability, low received municipal social service support, closeness of patient-caregiver relation, and short distance to patient's home. Significant positive associations within the dyads were found for HAD anxiety score (P < 0.0001), total NHP score (P < 0.0001), and GQL activity score (P < 0.0001) after adjustment for patient's age, sex, functional ability, and patient-caregiver relationship. CB score increased with amount of informal caregiver support, patient's age, and with low functional ability and low amount of municipal social service support. All these associations were constant across time.

    CONCLUSIONS: There was an association within the dyads regarding anxiety score, NHP score, and activity score. CB score was generally high.

  • 224.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Henrik Sjobring and the concept of individual psychology in psychiatry2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 2, p. 95-103Article in journal (Refereed)
  • 225.
    Palm, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Liss, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Fasching, Angelica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Hansell, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Transient glomerular hyperfiltration in the streptozotocin-diabetic Wistar Furth rat.2001In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 106, no 3, p. 175-82Article in journal (Refereed)
    Abstract [en]

    The glomerular hemodynamic response to streptozotocin (STZ)-induced experimental diabetes differs depending on metabolic control and rat strain used. The present study characterize the glomerular filtration rate (GFR) and other renal parameters, weekly up to eight weeks of diabetes in STZ-diabetic Wistar Furth rats. The STZ-treated rats became diabetic within 24 h after treatment and retained a blood glucose concentration of 20-25 mmol/l throughout the experimental period. The GFR was transiently increased during the first 3-5 weeks after induction of diabetes, but thereafter did not differ from control animals. The renal weight increased by approximately 50% during the first week after induction of diabetes, thereafter no further increase in weight occurred. The urinary flow rate and urinary osmolar excretion were approximately 10 times higher in diabetic animals when compared to non-diabetic animals. Although they remained markedly higher than in non-diabetic animals, both the urinary flow rate and the urinary osmolar excretion peaked after 3 weeks of diabetes and thereafter tended to decrease. The urinary sodium and potassium excretions did not differ between non-diabetic and diabetic animals. We conclude that the transient increase in the GFR seen in the human disease, occurs in Wistar Furth rats, which is in contrast to a majority of other rat strains, where the GFR is persistently increased.

  • 226.
    Patelis, Antonios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Author's response: Dysfunction of small airways and prevalence, airway responsiveness and inflammation in asthma: much more than small particle size of pet animal allergens2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 3, p. 198-198Article in journal (Refereed)
  • 227.
    Patelis, Antonios
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Dosanjh, Amrita
    Department of Pediatrics , Scripps Hospital , San Diego , CA , USA.
    Gunnbjörnsdottir, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Borres, Magnus P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Högman, Marieann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Alving, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Malinovschi, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    New data analysis in a population study raises the hypothesis that particle size contributes to the pro-asthmatic potential of small pet animal allergens.2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 1, p. 25-32Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The size of inhaled particles influences where they deposit and theoretically should be important for the development of airway inflammation and responsiveness. Our aim was to assess if sensitization to smaller-sized aeroallergens relates to higher prevalence of treated asthma, increased airway responsiveness, and airway and systemic inflammation.

    METHODS: Molecular-based IgE antibody determination was done in 467 subjects. Sensitized subjects were grouped based on the particle size of the aeroallergen: (1) Large particles only (mainly pollen); (2) Medium-sized particles (sensitized to mainly mite and mold and possibly to large particles); and 3) Small particles (sensitized to pet allergens and possibly to medium- and/or large-sized particles). Airway responsiveness to methacholine, exhaled nitric oxide (FENO), and serum eosinophil cationic protein (S-ECP) were measured. Asthma and rhinitis were questionnaire-assessed.

    RESULTS: Subjects sensitized to small particles had higher prevalence of treated asthma (35% versus 10%, P < 0.001), higher FENO50 (32 versus 17 ppb, P < 0.001), higher S-ECP (10 versus 7.5 ng/mL, P = 0.04), and increased bronchial responsiveness (dose-response slope, 5.6 versus 7.5, P < 0.001) compared with non-atopics. This was consistent after adjusting for potential confounders. Sensitization to only large or to medium and possibly also large aeroallergen particles was not related to any of these outcomes after adjustments.

    CONCLUSIONS: Sensitization to smaller particles was associated with a higher prevalence of asthma under treatment, higher airway responsiveness, and airway and systemic inflammation. Mapping of IgE sensitization to small particles might help to detect subjects having increased airway and systemic inflammation and bronchial responsiveness, indicating increased risk of developing asthma.

  • 228.
    Peterson, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Butler, Stephen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Margaretha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    A randomized controlled trial of exercise versus wait list in chronic tennis elbow (lateral epicondylosis)2011In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 116, no 4, p. 269-279Article in journal (Refereed)
    Abstract [en]

    Background.

    Chronic tennis elbow (lateral epicondylosis) is a common disorder. Like other chronic soft tissue pain conditions it is often difficult to treat successfully. The effects of exercise have been discussed but no convincing evidence has been put forward so far, and a simple protocol for exercise is lacking.

    Aims of the study.

    This study is a randomized, controlled, clinical trial of the effect of exercise versus expectation (wait-list) on pain, muscle strength, function, and quality of life in patients with longstanding lateral epicondylosis.

    Methods.

    Eighty-one subjects with tennis elbow lasting for more than three months were randomly allocated to an exercise group (n=40) or a reference group (n=41). The exercise group performed daily exercise, with weekly load increase, for three months. The reference group was wait listed, but otherwise followed in the same way. Outcome measures were pain during maximum voluntary muscle contraction (Cozen´s test) and pain during maximum muscle elongation with a load (modified Empty-can-test), muscle strength measured with a Chatillon MSE 100 hand-held dynamometer, and the Disability of the Arm, Shoulder and Hand (DASH) and the Gothenburg Quality of Life questionnaires.

    Results

    .The exercise group had greater and faster regression of pain, both during muscle contraction and muscle elongation, than the reference group (p=0.0005 and p=0.0016, respectively). There was a non-significant muscle strength difference between the groups, but no differences regarding DASH scores or quality of life measures.

    Conclusions

    .Exercise appears to be superior to expectation in reducing pain in chronic lateral epicondylosis.

  • 229.
    Pettersson, Karolina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Saers, Johannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sleep disturbances among Swedish soldiers after military service abroad2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 1, p. 65-69Article in journal (Refereed)
    Abstract [en]

    Aims Since 1956, more than 100,000 Swedish soldiers have served abroad on various international missions. The aim of this paper was to determine whether there was a connection between military service abroad and sleep disorders among Swedish soldiers. Methods The prevalence of sleep disturbances among 1,080 veterans from Kosovo and Afghanistan was compared with almost 27,000 Swedes from a general population sample, using propensity score matching and logistic regression. The sleep disturbances studied were habitual snoring, difficulty inducing sleep (DIS), difficulty maintaining sleep (DMS), early morning awakenings (EMA), and excessive daytime sleepiness (EDS). Insomnia was defined as having at least one of DIS, DMS, or EMA. The covariates used in the matching and adjustments were age, gender, smoking habits, BMI, education, ever having had asthma, moist snuff, and exercise habits. Results The veterans had a significantly lower prevalence of insomnia (26.2% versus 30.4%) and EDS (22.7% versus 29.4%) compared with a matched group from the reference population, using propensity score matching. Analyses with logistic regression showed that belonging to the military population was related to a lower risk of having DMS (adjusted OR (95% CI) 0.77 (0.64-0.91)), insomnia (OR 0.82 (0.71-0.95)), and EDS (OR 0.74 (0.63-0.86)), whereas no significant difference was found for snoring, DIS, and EMA. Conclusion Swedish veterans have fewer problems with insomnia and daytime sleepiness than the general Swedish population. The explanation of our findings may be the selection processes involved in becoming a soldier and when sampling personnel for military assignments abroad.

  • 230.
    Pettersson, U
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Encounters with adenovirus2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 2, p. 83-93Article, review/survey (Refereed)
    Abstract [en]

    In this paper I describe aspects of work on the human adenoviruses in which my laboratory has participated. It consists of two sections-one historic dealing with work performed in the previous century, and one dealing with the application of 'omics' technologies to understand how adenovirus-infected cells become reprogrammed to benefit virus multiplication.

  • 231.
    Pilebro, Björn
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Ctr Heart, Cardiol, SE-90185 Umea, Sweden..
    Suhr, Ole B.
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden..
    Näslund, Ulf
    Umea Univ, Dept Publ Hlth & Clin Med, Ctr Heart, Cardiol, SE-90185 Umea, Sweden..
    Westermark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Lindqvist, Per
    Umea Univ, Dept Surg & Perioperat Sci, Ctr Heart, Clin Physiol, SE-90185 Umea, Sweden..
    Sundstrom, Torbjorn
    Umea Univ, Dept Radiat Sci, Diagnost Radiol, SE-90185 Umea, Sweden..
    Tc-99m-DPD uptake reflects amyloid fibril composition in hereditary transthyretin amyloidosis2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 1, p. 17-24Article in journal (Refereed)
    Abstract [en]

    Aims In transthyretin amyloid (ATTR) amyloidosis various principal phenotypes have been described: cardiac, neuropathic, or a mixed cardiac and neuropathic. In addition, two different types of amyloid fibrils have been identified (type A and type B). Type B fibrils have thus far only been found in predominantly early-onset V30M and in patients carrying the Y114C mutation, whereas type A is noted in all other mutations currently examined as well as in wild-type ATTR amyloidosis. The fibril type is a determinant of the ATTR V30M disease phenotype. Tc-99m-DPD scintigraphy is a highly sensitive method for diagnosing heart involvement in ATTR amyloidosis. The objective of this study was to determine the relationship between ATTR fibril composition and Tc-99m-DPD scintigraphy outcome in patients with biopsy-proven ATTR amyloidosis. Methods Altogether 55 patients with biopsy-proven diagnosis of ATTR amyloidosis and amyloid fibril composition determined were examined by Tc-99m-DPD scintigraphy. The patients were grouped and compared according to their type of amyloid fibrils. Cardiovascular evaluation included ECG, echocardiography, and cardiac biomarkers. The medical records were scrutinized to identify subjects with hypertension or other diseases that have an impact on cardiac dimensions. Results A total of 97% with type A and none of the patients with type B fibrils displayed Tc-99m-DPD uptake at scintigraphy (p < 0.001). Findings from analyses of cardiac biomarkers, ECG, and echocardiography, though significantly different, could not differentiate between type A and B fibrils in individual patients. Conclusion In ATTR amyloidosis, the outcome of Tc-99m-DPD scintigraphy is strongly related to the patients' transthyretin amyloid fibril composition.

  • 232.
    Portala, Kamilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Waldenström, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    von Knorring, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Westermark, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Psychopathology and Personality Traits in Patients with Treated Wilson Disease Grouped According to Gene Mutations2008In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 113, no 1, p. 79-94Article in journal (Refereed)
    Abstract [en]

    Wilson disease (WD) is a recessively inherited copper storage disorder   mainly affecting liver and brain. Genotype/phenotype correlations have   been reported but as yet not regarding psychic symptoms. Our aim was to   investigate if a correlation might exist between genotype and phenotype   concerning psychopathology and/or personality traits in patients with treated WD. Nine homozygous and three compound heterozygous Swedish patients were retrospectively investigated, representing four different   mutation settings. Psychopathological symptoms were studied using the Comprehensive Psychopathological Rating Scale (CPRS), personality   traits using the Karo lin ska Scales of Personality (KSP) and mutations   were analyzed by manifold sequencing. Psychopathological symptoms: Patients with the Trp779Stop mutation had the lowest scores on the   total CPRS, due to less pronounced reported CPRS items, as compared to the other three groups of patients. Compound heterozygotes for the His1069Gln/Arg1319Stop mutation showed the highest total CPRS scores.   Personality traits: Patients homozygous for the Trp779Stop and the Thr977Met mutations had high scores on Psychopathy related scales whereas patients with His1069Gln/Arg1319Stop mutations had the lowest scores on these scales. Serum ceruloplasmin levels were undetectable in   all patients with the Trp779Stop and Thr977Met mutations. The results show a trend towards a genotype/phenotype correlation regarding psychopathological symptoms and personality traits in treated patients with WD. If replicable, these results might contribute to the elucidation of the possible clinical importance of functionally   deleterious gene mutations in WD psychopathology and personality traits.

  • 233.
    Rask-Andersen, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Asthma increase among farmers: a 12-year follow-up2011In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 116, no 1, p. 60-71Article in journal (Refereed)
    Abstract [en]

    Respiratory disease is a well known health hazard for farmers, but the long-term prognosis is less well known. This is a 12-year follow-up of an investigation of Swedish farmers, most of them dairy farmers. A questionnaire was mailed to all 418 farmers who were alive of the farmers originally participating in 1982. They were invited to an interview, spirometry, and blood sampling. Ninety-one per cent (380) of the farmers, 321 men and 59 women, responded to the questionnaire. The mean age was 56 years for the men and 55 years for the women. Of the group, 10% were smokers, 25% ex-smokers, and 65% had never smoked. The population estimate for asthma in the farmers was 8.9% in 1994 compared to 2% in 1982, and to 5.4%-6.6% in the general population in the region in 1982. Of the asthmatic subjects, one-third had positive RAST tests (radioallergosorbent tests). Almost 90% of the new onset asthma cases since 1982 had non-IgE-mediated asthma. Most of the IgE-mediated asthmatics had had symptoms for many years, while 70% of the non-IgE-mediated asthmatic farmers had no or only wheezing with colds 1982. Two new cases of hypersensitivity pneumonitis were identified, and 7.3% had experienced inhalation fever during the last 12 years. In general, individuals with asthma and chronic bronchitis who had left farming were in better health in 1994 as compared to 1982. In conclusion, farmers have an enhanced risk to develop asthma increasing with age. Asthma in farmers is often non-IgE-mediated.

  • 234.
    Rask-Andersen, Helge
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Li, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Löwenheim, Hubert
    Med Univ Innsbruck, Dept Otolaryngol, Innsbruck, Austria.;Med Campus Univ Oldenburg Sch Med & Hlth Sci, European Med Sch, Oldenburg, Germany.;Carl von Ossietzky Univ Oldenburg, Res Ctr Neurosensory Sci, Oldenburg, Germany.;Eberhard Karls Univ Tubingen, Tubingen Hearing Res Ctr, Dept Otolaryngol Head & Neck Surg, DE-72076 Tubingen, Germany..
    Mueller, Marcus
    Med Univ Innsbruck, Dept Otolaryngol, Innsbruck, Austria.;Med Campus Univ Oldenburg Sch Med & Hlth Sci, European Med Sch, Oldenburg, Germany.;Carl von Ossietzky Univ Oldenburg, Res Ctr Neurosensory Sci, Oldenburg, Germany.;Eberhard Karls Univ Tubingen, Tubingen Hearing Res Ctr, Dept Otolaryngol Head & Neck Surg, DE-72076 Tubingen, Germany..
    Pfaller, Kristian
    Carl von Ossietzky Univ Oldenburg, Cluster Excellence Hearing4all, Oldenburg, Germany..
    Schrott-Fischer, Annelies
    Med Univ Innsbruck, Inst Anat & Histol, Dept Histol & Mol Cell Biol, Innsbruck, Austria..
    Glueckert, Rudolf
    Med Univ Innsbruck, Inst Anat & Histol, Dept Histol & Mol Cell Biol, Innsbruck, Austria..
    Supernumerary human hair cells-signs of regeneration or impaired development?: A field emission scanning electron microscopy study2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 1, p. 11-19Article in journal (Refereed)
    Abstract [en]

    Background: Current attempts to regenerate cochlear sensorineural structures motivate further inspection of the human organ of hearing. Here, we analyzed the supernumerary inner hair cell (sIHC), a possible sign of regeneration and cell replacement. Methods: Human cochleae were studied using field emission scanning electron microscopy (FESEM; maximum resolution 2 nm) obtained from individuals aged 44, 48, and 58 years with normal sensorineural pure-tone average (PTA) thresholds (PTA < 20 dB). The wasted tissue was harvested during trans-cochlear approaches and immediately fixed for ultrastructural analysis. Results: All specimens exhibited sIHCs at all turns except at the extreme lower basal turn. In one specimen, it was possible to image and count the inner hair cells (IHCs) along the cochlea representing the 0.2 kHz-8 kHz region according to the Greenwood place/frequency scale. In a region with 2,321 IHCs, there were 120 scattered one-cell losses or 'gaps' (5%). Forty-two sIHCs were present facing the modiolus. Thirty-eight percent of the sIHCs were located near a 'gap' in the IHC row (+/- 6 IHCs). Conclusions: The prevalence of ectopic inner hair cells was higher than expected. The morphology and placement could reflect a certain ongoing regeneration. Further molecular studies are needed to verify if the regenerative capacity of the human auditory periphery might have been underestimated.

  • 235.
    Rasmussen, Ib Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Karlson, Britt-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Löfberg, Ann-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Biliary pancreatic portal fistula as a complication of chronic pancreatitis. A case report with review of the literature2006In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 111, no 3, p. 329-338Article in journal (Refereed)
    Abstract [en]

    In this study we describe an unusual complication in a patient suffering from chronic calcifying pancreatitis. The patient had a fistula between the common bile duct, the pancreatic duct, and the portal vein. He received supportive medical treatment and achieved long-term survival. A review of the literature including diagnosis, treatment and outcome of this rare complication is presented.

  • 236.
    Roman, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Karlsson, Oskar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Increased anxiety-like behavior but no cognitive impairments in adult rats exposed to constant light conditions during perinatal development2013In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 4, p. 222-227Article in journal (Refereed)
    Abstract [en]

    Background

    Shift-work is suggested to affect fetal development negatively. In particular, maternal hormonal disturbance arising from sleep deprivation or circadian rhythm changes may disturb fetal growth or lead to complications during pregnancy. Exposure to constant light is an environmental stressor that can affect the circadian system and has been shown to induce neurochemical and behavioral changes when used during the prenatal and/or postnatal period in experimental animals. However, studies investigating long-term effects of constant light in the offspring are sparse.

    Methods

    An accidental power outage resulted in pregnant females being housed under constant light (LL) conditions for seven days of the offspring perinatal development (embryonic day 20 to postnatal day 4). The long-term effects of constant light on the behavior in the adult offspring were assessed by means of open field, object recognition, and water maze tests.

    Results

    In adulthood, LL-animals displayed an intact recognition memory and no deficits in spatial learning or memory. In the open field test, LL-animals exhibited higher anxiety-like behavior, observed as significantly more thigmotaxis and less ambulation. These results were confirmed in the other behavioral tests as the LL-animals spent less time exploring the objects in the object recognition test, and showed thigmotactic behavior also in the water maze test.

    Conclusion

    The results confirm that early life experience can cause changes in brain development that shape brain function and add to the sparse literature on long-term effects of constant light conditions during perinatal development on specific behaviors in adulthood.

  • 237.
    Ronne-Engström, Elisabeth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Borota, Ljubisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kothimbakam, Raj
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lewén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Outcome from spontaneous subarachnoid haemorrhage: results from 2007-2011 and comparison with our previous series2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 1, p. 38-43Article in journal (Refereed)
    Abstract [en]

    Objectives

    The management of patients with spontaneous subarachnoid haemorrhage (SAH) has changed, in part due to interventions now being extended to patients who are older and in a worse clinical condition. This study evaluates the effects of these changes on a complete 5-year patient material.

    Methods

    Demographic data and results from 615 patients with SAH admitted from 2007 to 2011 were put together. Aneurysms were found in 448 patients (72.8%). They were compared with the aneurysm group (n = 676) from a previously published series from our centre (2001-2006). Linear regression was used to determine variables predicting functional outcome in the whole aneurysm group (2001-2011).

    Results

    Patients in the more recent aneurysm group were older, and they were in a worse clinical condition on admission. Regarding younger patients admitted in World Federation of Neurosurgical Societies SAH grading (WFNS) 3, there were fewer with a good outcome. In the whole aneurysm group 2001-2011, outcome was best predicted by age, clinical condition at admission, and the size of the bleeding, and not by treatment mode or localization of aneurysm.

    Conclusion

    It seems important for the outcome that aneurysms are treated early. The clinical course after that depends largely on the condition of the patient on admission rather than on aneurysm treatment method. This, together with the fact that older patients and those in worse condition are now being admitted, increases demands on neurointensive care. Further improvement in patient outcome depends on better understanding of acute brain injury mechanisms and improved neurointensive care as well as rehabilitation measures.

  • 238.
    Ronne-Engström, Elisabeth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Popek, Edith
    Symptomatic colloid cysts in the third ventricle of monozygotic twins2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 1, p. 59-62Article in journal (Refereed)
    Abstract [en]

    In this case report we describe colloid cysts in the third ventricles of monozygotic twin sisters. They were 26 years old when their condition was discovered. One woman was admitted to us on an emergency basis, with signs of high intracranial pressure such as unconsciousness and extension posturing. Her sister was also brought to the hospital since she had a history of attacks of headache. They were both operated with removal of the colloid cysts, and the clinical courses are described in the case report. In reviewing the literature another 30 familial cases were found. Of these were two pairs of monozygotic and one pair of dizygotic twins.

  • 239.
    Rosling, Agneta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Ros, Helena Salonen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Swenne, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    One-year outcome and incidence of anorexia nervosa and restrictive eating disorders among adolescent girls treated as out-patients in a family-based setting2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 1, p. 50-59Article in journal (Refereed)
    Abstract [en]

    Aims To study the 1-year outcome and to analyse predictors of outcome of a cohort of adolescent girls with anorexia nervosa (AN) or restrictive eating disorders not otherwise specified (EDNOSr) treated as out-patients in a family-based programme at a specialized eating disorder service. To calculate the incidence of anorexia nervosa among treatment-seeking girls younger than 18 in Uppsala County from 2004 to 2006. Methods A total of 168 female patients were offered treatment, and 141 were followed-up 1 year after starting treatment, 29 with AN and 112 with EDNOSr. Results Of the 29 girls who initially had AN, 6 (20%) had a good outcome and were free of any form of eating disorder at follow-up; only 1 (3%) had AN. Of the patients with EDNOSr, 54 (48%) had a good outcome and were free of eating disorders. Three (3%) had a poor outcome and had developed AN. The incidence of AN was 18/100,000 person-years in girls younger than 12 and 63/100,000 in girls younger than 18. Conclusion Restrictive eating disorders, including AN, in children and adolescents can be successfully treated in a family-based specialized out-patient service without in-patient care.

  • 240.
    Runeson, Roma Broberg
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Vingård, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lampa, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Wahlstedt, K.
    Health among Swedish employees and financial situation, education, and managerial responsibility: A longitudinal study2012In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 4, p. 445-452Article in journal (Refereed)
    Abstract [en]

    Background. The present study is part of a 3-year longitudinal study on work and health among employees in the public sector in Sweden. The aim was to study associations between self-rated health (SRH) and financial situation, education, and managerial responsibility. Methods. Of the 9003 employees, 7533 answered the baseline questionnaires (84%). Altogether 9373 subjects received the follow-up questionnaire, and 6617 subjects responded (71%). In total 4240 completed the questionnaire on both occasions, and this group comprised the study population. SRH consisted of the response to a single question: 'In general, would you say your health is excellent, very good, good, poor, or very poor?' The health was investigated in terms of the development of health status in the 3-year follow-up. The exposure factors were: financial situation, education, and managerial responsibility. Odds ratios were analysed using logistic regressions. Results. Good financial situation and further education were predictors in maintaining good health and in avoiding poor health. The analysis also indicated the following determinants of sustained good SRH: having a good financial situation (OR 1.99 at baseline and OR 1.87 at follow-up), having a further education compared to lower education (OR 1.17 at baseline), and not having a worsening financial situation between baseline and follow-up (OR 0.53). Conclusion. Financial situation and educational level were important factors that influence the subjective perception of health.

  • 241.
    Rutebemberwa, Elizeus
    et al.
    Makerere University School of Public Health, Kampala, Uganda.
    Mpeka, Betty
    Abt Associates, Kampala, Uganda.
    Pariyo, George
    Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
    Peterson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Mworozi, Edison
    Department of Paediatrics and Child Health, Makerere University Medical School, Kampala, Uganda.
    Bwanga, Freddie
    Department of Microbiology, Makerere University Faculty of Medicine, Kampala, Uganda.
    KäLlander, Karin
    Malaria Consortium, London, United Kingdom.
    High prevalence of antibiotic resistance in nasopharyngeal bacterial isolates from healthy children in rural Uganda: A cross-sectional study2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 4, p. 249-256Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In Uganda, the main causes of death in children under 5 years of age are malaria and pneumonia-often due to delayed diagnosis and treatment. In preparation for a community case management intervention for pneumonia and malaria, the bacterial composition of the nasopharyngeal flora and its in vitro resistance were determined in children aged five or under to establish baseline resistance to commonly used antibiotics.

    METHODS: In a population-based survey in April 2008, nasopharyngeal specimens were collected from 152 randomly selected healthy children under 5 years of age in the Iganga/Mayuge Health and Demographic Surveillance Site (HDSS). Medical history and prior treatment were recorded. Demographic characteristics and risk factors for carriage of resistant strains were obtained from the HDSS census. Bacteria were isolated and analysed for antibiotic susceptibility using disk diffusion and E test.

    RESULTS: Streptococcus pneumoniae (S. pneumoniae) carriage was 58.6%, and, while most (80.9%) isolates had intermediate resistance to penicillin, none was highly resistant. Whereas no isolate was resistant to erythromycin, 98.9% were resistant to trimethoprim-sulphamethoxazole (co-trimoxazole).

    CONCLUSIONS: In vitro resistance in S. pneumoniae to co-trimoxazole treatment was high, and the majority of isolates had intermediate resistance to penicillin. To inform treatment policies on the clinical efficacy of current treatment protocols for pneumonia in health facilities and at the community level, routine surveillance of resistance in pneumonia pathogens is needed as well as research on treatment efficacy in cases with resistant strains. Improved clinical algorithms and diagnostics for pneumonia should be developed.

  • 242.
    Ryden, Ingvar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Reference values of thirty-one frequently used laboratory markers for 75-year-old males and females2012In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 3, p. 264-272Article in journal (Refereed)
    Abstract [en]

    Background.

    We have previously reported reference values for common clinical chemistry tests in healthy 70-year-old males and females. We have now repeated this study 5 years later to establish reference values also at the age of 75. It is important to have adequate reference values for elderly patients as biological markers may change over time, and adequate reference values are essential for correct clinical decisions.

    Methods.

    We have investigated 31 frequently used laboratory markers in 75-year-old males (n = 354) and females (n = 373) without diabetes. The 2.5 and 97.5 percentiles for these markers were calculated according to the recommendations of the International Federation of Clinical Chemistry.

    Results.

    Reference values are reported for 75-year-old males and females for 31 frequently used laboratory markers.

    Conclusion.

    There were minor differences between reference intervals calculated with and without individuals with cardiovascular diseases. Several of the reference intervals differed from Scandinavian reference intervals based on younger individuals (Nordic Reference Interval Project).

  • 243.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    The type I interferon system in the etiopathogenesis of autoimmune diseases2011In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 116, no 4, p. 227-237Article, review/survey (Refereed)
    Abstract [en]

    Many patients with systemic autoimmune diseases have signs of a continuous production of type I interferon (IFN) and display an increased expression of IFN-alpha-regulated genes. The reason for the on-going IFN-alpha synthesis in these patients seems to be an activation of plasmacytoid dendritic cells (pDCs) by immune complexes (ICs), consisting of autoantibodies in combination with DNA or RNA-containing autoantigens. Such interferogenic ICs are internalized via the Fc gamma RIIa expressed on pDCs, reach the endosome, and stimulate Toll-like receptor (TLR)-7 or -9, which subsequently leads to IFN-alpha gene transcription. Variants of genes involved in both the IFN-alpha synthesis and response have been linked to an increased risk to develop systemic lupus erythematosus (SLE) and other autoimmune diseases. Among these autoimmunity risk genes are IFN regulatory factor 5 (IRF5), which is involved in TLR signaling, and the signal transducer and activator of transcription 4 (STAT4) that interacts with the type I IFN receptor. Several other gene variants in the IFN signaling pathway also confer an increased risk to develop an autoimmune disease. The observations that IFN-alpha therapy can induce autoimmunity and that many autoimmune conditions have an on-going type I IFN production suggest that the type I IFN system has a pivotal role in the etiopathogenesis of these diseases. Possible mechanisms behind the dysregulated type IFNsystem in autoimmune diseases and how the IFN-alpha produced can contribute to the development of an autoimmune process will be reviewed.

  • 244.
    Sahlén, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Nilsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Carlsson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Norlén, Bo Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Ronquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Secretions from seminal vesicles lack characteristic markers for prostasomes2010In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 115, no 2, p. 107-112Article in journal (Refereed)
    Abstract [en]

    Background. Prostasomes are suggested to be produced in the prostate gland. Although biochemical studies support this, some immunohistochemical findings indicate that also the seminal vesicles could be a source of prostasomes. Therefore, we have compared the secretion of the vesicles with that of the prostate using biochemical and ultrastructural techniques. Methods. Ultracentrifuged pellets of substance from seminal vesicle secretions were analysed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and flow cytometry. The secretory cells of the seminal vesicles were examined with transmission electron microscopy. These findings were then compared with published results from similar studies of the prostate secretory cells. Results. In SDS-PAGE, the seminal vesicle pellets lacked the three prostasome-characteristic CD-markers, namely CD10, CD13, and CD26, but expressed two proteins of about 55 kDa and 70 kDa, corresponding to clusterin and heat shock protein (HSP70). Flow cytometry showed the presence of secretion particles in the seminal pellet, although of a smaller size than that of the prostasomes. Electron microscopy of the luminal part of the cells in the seminal vesicles demonstrated many secretion granules, each enclosed in a vesicle with a size of about 1 mum. Conclusions. Pelleted seminal vesicle secretion is different to prostate secretion in several ways. No prostasome characteristics were detected in the pelleted seminal vesicle secretion.

  • 245.
    Salci, Konstantin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Goiny, Michel
    Contant, Charles F.
    Piper, Ian
    Nilsson, Pelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Metabolic effects of a late hypotensive insult combined with reduced intracranial compliance following traumatic brain injury in the rat2010In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 115, no 4, p. 221-231Article in journal (Refereed)
    Abstract [en]

    Introduction. Traumatic brain injury makes the brain vulnerable to secondary insults. Post-traumatic alterations in intracranial dynamics, such as reduced intracranial compliance (IC), are thought to further potentiate the effects of secondary insults. Reduced IC combined with intracranial volume insults leads to metabolic disturbances in a rat model. The aim of the present study was to discern whether a post-traumatic hypotensive insult in combination with reduced IC caused more pronounced secondary metabolic disturbances in the injured rat brain. Materials and methods. Rats were randomly assigned to four groups (n = 8/group): 1) trauma with hypotension; 2) trauma and reduced IC with hypotension; 3) sham injury with hypotension; and 4) sham injury and reduced IC with hypotension. A weight drop model of cortical contusion trauma was used. IC was reduced by gluing rubber film layers on the inside of bilateral bone flaps before replacement. Microdialysis probes were placed in the perimeter of the trauma zone. Hypotension was induced 2 h after trauma. Extracellular (EC) levels of lactate, pyruvate, hypoxanthine, and glycerol were analyzed. Results. The trauma resulted in a significant increase in EC dialysate levels of lactate, lactate/pyruvate ratio, hypoxanthine, and glycerol. A slight secondary increase in lactate was noted for all groups but group 2 during hypotension, otherwise no late effects were seen. There were no effects of reduced IC. Discussion. In conclusion, reduced IC did not increase the metabolic disturbances caused by the post-traumatic hypotensive insult. The results suggest that a mild to moderate hypotensive insult after initial post-traumatic resuscitation may be tolerated better than an early insult before resuscitation.

  • 246.
    Salih Joelsson, Lana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Berglund, Anna
    Uppsala University, National Centre for Knowledge on Men.
    Wånggren, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Lood, Mikael
    Orebro Univ Hosp, Fertil Unit, Dept Womens Hlth, Orebro, Sweden.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Tydén, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Do subfertile women adjust their habits when trying to conceive?2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 3, p. 184-191Article in journal (Refereed)
    Abstract [en]

    AbstractAIM:

    The aim of this study was to investigate lifestyle habits and lifestyle adjustments among subfertile women trying to conceive.

    MATERIALS AND METHODS:

    Women (n = 747) were recruited consecutively at their first visit to fertility clinics in mid-Sweden. Participants completed a questionnaire. Data were analyzed using logistic regression, t tests, and chi-square tests.

    RESULTS:

    The response rate was 62% (n = 466). Mean duration of infertility was 1.9 years. During this time 13.2% used tobacco daily, 13.6% drank more than three cups of coffee per day, and 11.6% consumed more than two glasses of alcohol weekly. In this sample, 23.9% of the women were overweight (body mass index, BMI 25-29.9 kg/m(2)), and 12.5% were obese (BMI ≥30 kg/m(2)). Obese women exercised more and changed to healthy diets more frequently than normal-weight women (odds ratio 7.43; 95% confidence interval 3.7-14.9). Six out of ten women (n = 266) took folic acid when they started trying to conceive, but 11% stopped taking folic acid after some time. Taking folic acid was associated with a higher level of education (p < 0.001).

    CONCLUSIONS:

    Among subfertile women, one-third were overweight or obese, and some had other lifestyle factors with known adverse effects on fertility such as use of tobacco. Overweight and obese women adjusted their habits but did not reduce their body mass index. Women of fertile age would benefit from preconception counseling, and the treatment of infertility should routinely offer interventions for lifestyle changes.

    KEYWORDS:

    Alcohol consumption; assisted reproduction; diet; infertility; lifestyle; obesity; pregnancy; tobacco use

  • 247.
    Sandberg, Monica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Jansson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Effects of cyclooxygenase inhibition on insulin release and pancreatic islet blood flow in rats2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 4, p. 316-323Article in journal (Refereed)
    Abstract [en]

    Objectives. To examine the effects of inhibition of cyclooxygenase (COX) on islet hormone secretion in vitro and on pancreatic islet blood flow in vivo. Methods. Insulin release was measured in a static incubation system of islets isolated from Wistar-F rats after inhibition of COX-1 and COX-2 with SC 560 (COX-1), FR 122047 (COX-1), rofecoxib (COX-2), or indomethacin (both COX-1 and COX-2). In other rats organ blood flow values were measured with a microsphere technique during both normo- and hyperglycemia after administration of these enzyme inhibitors. Results. Serum insulin values were lower after pretreatment with a COX-1 inhibitor or a non-selective COX inhibitor in both control and glucose-injected rats in vivo, whereas COX-2 inhibition had no such effects. However, inhibition of COX had only minor effects on insulin release in vitro. Inhibition of COX affected neither total pancreatic nor islet blood flow in normoglycemic rats. Hyperglycemia caused an increase in both these flow values and in the duodenum. The increase in total pancreatic and duodenal blood flow was prevented by inhibition of COX-2 or non-selective COX inhibition. However, no effects on islet blood flow were seen after COX inhibition. Conclusion. Inhibition of COX affects insulin release and blood glucose concentrations in vivo. However, COX inhibition has only minor effects on pancreatic islet blood flow, but prevents the glucose-induced increase in total pancreatic blood flow.

  • 248.
    Sandblom, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Granroth, Sofie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rasmussen, Ib Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    TPS, CA 19-9, VEGF-A, and CEA as diagnostic and prognostic factors in patients with mass lesions in the pancreatic head2008In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 113, no 1, p. 57-64Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Although numerous tumour markers are available for periampullary tumours, including pancreatic cancer, their specificity and sensitivity have been questioned. MATERIALS AND METHODS: To assess the diagnostic and prognostic values of tissue polypeptide specific antigen (TPS), carbohydrate antigen 19-9 (CA 19-9), vascular endothelial growth factor (VEGF-A), and carcinoembryonic antigen (CEA) we took serum samples in 56 patients with mass lesions in the pancreatic head. Among these patients, further investigations revealed pancreatic cancer in 20 patients, other malignant diseases in 12 and benign conditions in 24. RESULTS: Median CEA in all patients was 3.4 microg/L (range 0.5-585.0), median CA 19-9 was105 kU/L (range 0.6-1 300 00), median TPS 123.5 U/L (range 15.0-3350) and median VEGF-A 132.5 ng/L (range 60.0-4317). Area under the curve was 0.747, standard error (standard error [SE] =0.075) for CEA, 0.716 (SE=0.078) for CA 19-9 and 0.822 (SE=0.086) for TPS in ROC plots based on the ability of the tumours to distinguish between benign and malignant conditions. None of the markers significantly predicted survival in the subgroup of patients with pancreatic cancer. DISCUSSION: Our study shows that the markers may be used as fairly reliable diagnostic tools, but cannot be used to predict survival.

  • 249.
    Sandegren, Linus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Selection of antibiotic resistance at very low antibiotic concentrations2014In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, no 2, p. 103-107Article, review/survey (Refereed)
    Abstract [en]

    Human use of antibiotics has driven the selective enrichment of pathogenic bacteria resistant to clinically used drugs. Traditionally, the selection of resistance has been considered to occur mainly at high, therapeutic levels of antibiotics, but we are now beginning to understand better the importance of selection of resistance at low levels of antibiotics. The concentration of an antibiotic varies in different body compartments during treatment, and low concentrations of antibiotics are found in sewage water, soils, and many water environments due to natural production and contamination from human activities. Selection of resistance at non-lethal antibiotic concentrations (below the wild-type minimum inhibitory concentration) occurs due to differences in growth rate at the particular antibiotic concentration between cells with different tolerance levels to the antibiotic. The minimum selective concentration for a particular antibiotic is reached when its reducing effect on growth of the susceptible strain balances the reducing effect (fitness cost) of the resistance determinant in the resistant strain. Recent studies have shown that resistant bacteria can be selected at concentrations several hundred-fold below the lethal concentrations for susceptible cells. Resistant mutants selected at low antibiotic concentrations are generally more fit than those selected at high concentrations but can still be highly resistant. The characteristics of selection at low antibiotic concentrations, the potential clinical problems of this mode of selection, and potential solutions will be discussed.

  • 250. Sandler, S
    et al.
    Nilsson, B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Andersson, A
    Cryopreservation of mouse pancreatic islets: effects of human serum on islet survival.1987In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 92, no 2, p. 177-184Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to compare the survival of cryopreserved mouse pancreatic islets frozen in the presence of either a simple salt solution (Hanks' balanced salt solution) or a complete tissue culture medium (RPMI 1640). Moreover, the addition of 10% human serum to the freezing solutions was evaluated. Collagenase isolated islets were kept in culture for three days, before being cooled at a rate of 5 degrees C/min or 25 degrees C/min to -70 degrees C, at which temperature the islets were transferred to liquid nitrogen. All freezing media were supplemented with 2 M dimethylsulphoxide as cryoprotectant. The islets were rapidly thawed at 37 degrees C and subsequently cultured for another three days. The recovery of islets was higher when the more rapid cooling rate was used and the addition of serum further improved the recovery. Compared to non-frozen cultured islets there was a loss of cells in all groups of cryopreserved islets, as measured by their DNA content, and this was accompanied by a lowered insulin content. All groups of frozen-thawed islets responded to a high glucose stimulus in vitro with a 5-9 fold increase in insulin secretion. There was no obvious advantage of using a complete tissue culture medium for islet cryopreservation, but the addition of serum had some beneficial effects. Data obtained from non-frozen control islets suggest that human serum slightly impairs the function of mouse pancreatic B-cells.

234567 201 - 250 of 322
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