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  • 252551.
    Örnskov, E.
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry.
    Linusson, A.
    Folestad, S.
    Determination of dissociation constants of labile drug compounds by capillary electrophoresis2003In: J. of Pharmaceutical and Biomedical Analysis, no 33, p. 379-391Article in journal (Refereed)
  • 252552.
    Örnskov, Eivor
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry, Analytical Chemistry.
    Physicochemical and Biopharmaceutical Characterisation of Small Drug Molecules by Capillary Electrophoresis2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Capillary Electrophoresis (CE) was explored as a means for physicochemical and biopharmaceutical characterisation of small drug molecules. Special attention was paid to the characterisation of acid-base and lipophilic properties of drug compounds by analysing their migration behaviour in different CE systems. The thesis comprises an overview of the field together with separate studies on the different topics.

    The utility of CE for the determination of pKa of labile drug compounds was investigated. A general methodology was developed comprising key steps such as the use of a stabilising sample diluent, electromigration injection, and analyte characterisation by UV-Vis spectroscopy. The methodology was successfully applied for two sets of drug compounds, labile at low and high pH, respectively.

    CE was also evaluated for experimental modelling of passive intestinal membrane permeability by studying analyte migration in liposomal, microemulsion and micellar electrolytes. Good correlation is reported between CE migration and Caco-2 cell absorption estimates and for in vitro inhibition of thrombin. Interestingly, a slightly better correlation was obtained for liposomal electrolytes.

    The utility of liposomes in CE was further extended by developing a novel procedure for immobilising liposomes inside fused silica capillaries. This approach enabled direct on-line coupling of liposome CE to high sensitivity mass spectrometry. The utility of liposome-coated capillaries is demonstrated for estimating drug passive intestinal membrane permeability. Its use in biopharmaceutical drug profiling is discussed.

    Utilising advanced molecular descriptors, commonly applied to in silico prediction of passive intestinal membrane permeability, migration of analytes in micellar CE systems could be well predicted. The novel approach was based on hierarchical multivariate analytics and use of molecular descriptors for both analytes and micellar media surfactants. Demonstrated results propose that the CE format could be useful to validate how representative molecular descriptors are for describing molecular behaviour in complex liquid media, e.g. physiological systems.

    List of papers
    1. Determination of Dissociation Constants of Labile Drug Compounds by Capillary Electrophoresis
    Open this publication in new window or tab >>Determination of Dissociation Constants of Labile Drug Compounds by Capillary Electrophoresis
    2003 In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 33, p. 379-391Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91392 (URN)
    Available from: 2004-02-13 Created: 2004-02-13Bibliographically approved
    2. Statistical Molecular Design, Parallel Synthesis and Biological Evaluation of a Library of Thrombin Inhibitors
    Open this publication in new window or tab >>Statistical Molecular Design, Parallel Synthesis and Biological Evaluation of a Library of Thrombin Inhibitors
    Show others...
    2001 In: Journal of Medicinal Chemistry, Vol. 44, p. 3424-3439Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91393 (URN)
    Available from: 2004-02-13 Created: 2004-02-13Bibliographically approved
    3. Experimental Modeling of Passive Drug Absorption by Capillary Electrophoresis using Liposomal, Micellar and Microemulsion Electrolytes
    Open this publication in new window or tab >>Experimental Modeling of Passive Drug Absorption by Capillary Electrophoresis using Liposomal, Micellar and Microemulsion Electrolytes
    In: Journal of Pharmacy & PharmacologyArticle in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-91394 (URN)
    Available from: 2004-02-13 Created: 2004-02-13Bibliographically approved
    4. Method for Immobilization of Liposomes in Capillary Electrophoresis by Electrostatic Interaction with Derivatized Agarose
    Open this publication in new window or tab >>Method for Immobilization of Liposomes in Capillary Electrophoresis by Electrostatic Interaction with Derivatized Agarose
    Show others...
    2002 In: Electrophoresis, Vol. 23, no 19, p. 3381-3384Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91395 (URN)
    Available from: 2004-02-13 Created: 2004-02-13Bibliographically approved
    5. Immobilised-Liposome Capillary Electrophoresis - On-line Mass Spectrometry for Biopharmaceutical Drug Profiling
    Open this publication in new window or tab >>Immobilised-Liposome Capillary Electrophoresis - On-line Mass Spectrometry for Biopharmaceutical Drug Profiling
    Show others...
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-91396 (URN)
    Available from: 2004-02-13 Created: 2004-02-13 Last updated: 2011-03-21
    6. Hierarchical Multivariate Modelling and Prediction of MEKC Migration using Analyte and Micellar Media Molecular Descriptors
    Open this publication in new window or tab >>Hierarchical Multivariate Modelling and Prediction of MEKC Migration using Analyte and Micellar Media Molecular Descriptors
    In: ElectrophoresisArticle in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-91397 (URN)
    Available from: 2004-02-13 Created: 2004-02-13Bibliographically approved
  • 252553.
    Örnskov, Eivor
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Analytisk kemi.
    Physicochemical Characterisation of Small Drug Molecules by Capillary Electrophoresis2001Licentiate thesis, monograph (Other scientific)
  • 252554.
    Örnskov, Eivor
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry, Analytical Chemistry.
    Gottfries, Johan
    Erickson, Magnus
    Folestad, Staffan
    Experimental Modeling of Passive Drug Absorption by Capillary Electrophoresis using Liposomal, Micellar and Microemulsion ElectrolytesIn: Journal of Pharmacy & PharmacologyArticle in journal (Refereed)
  • 252555.
    Örnskov, Eivor
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry, Analytical Chemistry.
    Linusson, Anna
    Folestad, Staffan
    Determination of Dissociation Constants of Labile Drug Compounds by Capillary Electrophoresis2003In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 33, p. 379-391Article in journal (Refereed)
  • 252556.
    Örnskov, Eivor
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry, Analytical Chemistry.
    Linusson, Anna
    Johansson, Erik
    Folestad, Staffan
    Hierarchical Multivariate Modelling and Prediction of MEKC Migration using Analyte and Micellar Media Molecular DescriptorsIn: ElectrophoresisArticle in journal (Refereed)
  • 252557. Örnskov, Eivor
    et al.
    Ullsten, Sara
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry.
    Söderberg, Lennart
    Markides, Karin
    Folestad, Staffan
    Method for immobilization of liposomes in capillary electrophoresis2002In: Electrophoresis, Vol. 23, no 19, p. 3381-3384Article in journal (Refereed)
  • 252558.
    Örnskov, Eivor
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry, Analytical Chemistry.
    Ullsten, Sara
    Söderberg, Lennart
    Markides, Karin
    Folestad, Staffan
    Method for Immobilization of Liposomes in Capillary Electrophoresis by Electrostatic Interaction with Derivatized Agarose2002In: Electrophoresis, Vol. 23, no 19, p. 3381-3384Article in journal (Refereed)
  • 252559.
    Örnskov, Eivor
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry.
    Ullsten, Sara
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry.
    Söderberg, Lennart
    Surface Biotechnology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry.
    Markides, Karin
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry.
    Folestad, Staffan
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry.
    Method for immobilization of liposomes in capillary electrophoresis by electrostatic interaction with derivatized agarose2002In: Electrophoresis, ISSN 3381-3384, Vol. 23, p. 3381-3384Article in journal (Refereed)
    Abstract [en]

    A novel procedure for immobilization of liposomes inside fused-silica capillaries is

    demonstrated. First, the inner wall of the capillaries was coated with a positively

    charged polymer, composed of derivatized agarose. Subsequently, negatively charged

    liposomes were immobilized by electrostatic interaction on the polymer coating. The

    developed liposome coated capillaries were used as a nanoseparation tool for studying

    interactions between small drug compounds and liposomes. Part of this work was

    presented at the 15th International Symposium on Microscale Separations and Analysis,

    HPCE 2002, Stockholm, Sweden, April 2002.

  • 252560.
    Örs, Makbule
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Användning av duloxetin, amitriptylin och pregabalin vid fibromyalgi – jämförelse av behandling hos vuxna kvinnor2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Introduktion: Fibromyalgi är en sjukdom som är vanligare hos kvinnor än män. Cirka 2–4 % av Sveriges befolkning lider av sjukdomen och det är liknande siffror i andra delar av världen. För att få diagnosen fibromyalgi måste vissa kriterier uppfyllas, bland annat ska man ha en långvarig smärta i över tre månader. Även sömnbesvär och trötthet är vanliga besvär vid sjukdomen. I dagsläget finns det inga godkända läkemedel med indikationen fibromyalgi. Men vissa läkemedelsgrupper t.ex. tricykliska antidepressiva, antikonvulsiva och serotonin-noradrenalin återupptagshämmare har i kliniska studier visat god effekt hos patienter med fibromyalgi.

    Syfte: Det är många som har fibromyalgi i Sverige men inget läkemedel med den indikationen finns. Därav syftet med studien, att jämföra behandling av fibromyalgi hos vuxna kvinnor med duloxetin, amitriptylin och/eller pregabalin.

    Metod: En systematisk litteratursökning efter placebokontrollerade randomiserade studier och systematiska översikter gjordes i databaserna PubMed och Cochran samt via Läkemedelsverkets hemsida. De identifierade artiklarna kvalitetsgranskades enligt SBUs mallar för randomiserade studier respektive systematiska översikter.

    Resultat: Totalt identifierades 4 artiklar som uppfyllde inklusionskriterierna. Av dessa dömdes 3 vara av medelhög kvalitet och 1 av låg kvalitet. I studierna visades att pregabalin och duloxetin hade, både i monoterapi och i kombination, en symtomlindrande effekt på smärtan hos patienter med fibromyalgi. Detta definierades som en sänkning med minst 40 mm på VAS-skalan. Ingen av de randomiserade kontrollerade studierna hade studerat amitriptylins effekter men den används idag framförallt mot sömnbesvär och tas i låg dos innan sänggående.

    Konklusion: Det vetenskapliga underlaget är svagt och behöver stärkas, framförallt på symtomen sömn och trötthet hos fibromyalgipatienter.

  • 252561. Örstavik, K.
    et al.
    Namer, B.
    Schmidt, Roland
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Schmelz, M.
    Hilliges, M.
    Weidner, C.
    Carr, R.W.
    Handwerker, H.
    Jorum, E.
    Torebjörk, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Abnormal function of C-fibers in patients with diabetic neuropathy2006In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 26, no 44, p. 11287-11294Article in journal (Refereed)
    Abstract [en]

    The mechanisms underlying the development of painful and nonpainful neuropathy associated with diabetes mellitus are unclear. We have obtained microneurographic recordings from unmyelinated fibers in eight patients with diabetes mellitus, five with painful neuropathy, and three with neuropathy without pain. All eight patients had large-fiber neuropathy, and seven patients had pathological thermal thresholds in their feet, indicating the involvement of small-caliber nerve fibers. A total of 163 C-fibers were recorded at knee level from the common peroneal nerve in the patients (36-67 years old), and these were compared with 77 C-fibers from healthy controls (41-64 years old). The ratio of mechano-responsive to mechano-insensitive nociceptors was similar to 2:1 in the healthy controls, whereas in the patients, it was 1:2. In patients, a fairly large percentage of characterized fibers (12.5% in nonpainful and 18.9% in painful neuropathy) resembled mechano-responsive nociceptors that had lost their mechanical and heat responsiveness. Such fibers were rarely encountered in age-matched controls (3.2%). Afferent fibers with spontaneous activity or mechanical sensitization were found in both patient groups. We conclude that small-fiber neuropathy in diabetes affects receptive properties of nociceptors that leads to an impairment of mechano-responsive nociceptors.

  • 252562.
    Örtenblad, Linda
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of ALM.
    Idunas äpplen. Fredrika Bremers bokdonation till Högre lärarinneseminariet2011Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In the early 1860´s, the author and opinion former Fredrika Bremer made a large donation of books to Högre lärarinneseminariet, which is the first governmental institute for higher education of women in Sweden. The aim of this thesis is to describe the collection of donated books as well as to extract information regarding Bremer's international network of contacts, her views on women's education and her relation to Högre lärarinneseminariet. Furthermore, the aim is to highlight the unique relationship between Fredrika Bremer's private collection of the books and the library of Högre lärarinneseminariet from a gender perspective. A handwritten list of the 321 titles constitutin the donation has been preserved in the seminar archive and three quarters of the books have been re-discovered in a bookcase at Årsta castle. The donation is characterized by its double origin as stamps and personal dedications remain as permanent traces in the books. The archive list of the donation defines the scope of the current thesis. A sub-population of the books was selected for a more thorough investigation which was performed according to a bibliographical form. By considering each individual book as an artefact and the donation as its context, information was derived both from the individual book as well as from the book in relation to the collection as a whole. The investigation shows that the collection reflects Fredrika Bremer's areas of interest, her travels and her contacts with other writers throughout the world. The donation of the books, as well as the Iduna statue which she also donated, confirms that she saw her vision of a college being realized in Högre lärarinneseminariet. She was also aware of her own efforts for women's education and emancipation, and her significance as a role model for future students at the school. There is a high cultural history value in the preservation of Fredrika Bremer's book collection and it is desirable to make the collection more accessible for research.

  • 252563. Örtendahl, Monica
    et al.
    Uttermalm, Alf
    Simonsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Näsman, Per
    Wallsten, Tuula
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Estimated Time for Occurrence of Smoking-Related Consequences among Pregnant and Non-Pregnant Women2009In: International Journal of Environmental Research and Public Health, ISSN 1660-4601, Vol. 6, no 5, p. 1665-1675Article in journal (Refereed)
    Abstract [en]

    Objectives: To study time estimates by women smokers for when smokingrelated consequences will occur given continuing or quitting smoking. The relationship of these estimates to pregnancy and intent to quit smoking was also investigated. Methods: Over a two-week period, eighty women, selected to constitute four subgroups formed by pregnant vs. non-pregnant and trying vs. not trying to quit smoking, rated times at which they would expect smoking-related consequences to occur given continuing or quitting smoking. Results: Somatic health consequences were estimated to occur later than consequences related to mood and social relations. All consequences were estimated to occur later given quitting smoking. Pregnancy had an effect on the estimated time that consequences would occur, with pregnant women estimating earlier occurrence of consequences related to mood and social relations than non-pregnant women did. Conclusion: Health messages should stress consequences for somatic health in quitting smoking, since outcomes later in time might have too low a value to exert a positive effect on decisions to quit smoking.

  • 252564.
    Örtenhed, Kristina
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Law, Department of Law.
    Bosättningsanknytningar i gränsöverskridande familjerättsförhållanden: En internationellt privat- och processrättslig studie2006Doctoral thesis, monograph (Other academic)
    Abstract [en]

    In Swedish international family law, domicile (“hemvist”) is the most important connecting factor, with regard to determining the competent court and the law applicable to a dispute. This thesis aims to clarify the criteria for domicile, and other connecting factors based on a person’s residence, primarily from the point of view of Swedish international family law. Another purpose is to analyse and find explanations for the increasing importance of the domicile principle in Swedish international family law legislation and in international legislative co-operation.

    The thesis contains a comparative survey of the use and meaning of the concept of domicile as connecting factor in Sweden and the other Nordic countries, in particular within the scope of the so called Nordic Family Law Convention and the Nordic Inheritance Convention which both are instruments of private international law.

    Another purpose is to find explanations for the choice and success of habitual residence as a connecting factor in the Hague Conventions and to clarify the meaning of the expression. The concept is of crucial importance for the application of the 1980 Hague Convention on the Civil Aspects of International Child Abduction, ratified by Sweden. The author analyses, on the basis of Swedish case law, the extent to which the Swedish courts’ interpretation of the Convention’s concept of habitual residence (“hemvist”) is in compliance with the intentions of the Hague Convention.

    The thesis includes an overview of German and Swiss private international law. In these countries the domicile principle is based on two different connecting factors, namely domicile (“Wohnsitz”) and habitual residence (“gewöhnlicher Aufenthalt”).

    Swedish legislation and case law plays a central role in the analysis of the thesis.

  • 252565.
    Örtenhed, Kristina
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Law, Department of Law. Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Law, Department of Law.
    Hemvistbedömningen vid olovligt kvarhållande eller bortförande av barn2002In: Juridisk Tidskrift, p. 929-938Article in journal (Other scientific)
  • 252566.
    Örthagen, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics.
    Sensory profiles and consumer acceptance of rye bread: - the effect of addition of whole rye kernels2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Forskning visar att fullkorn, råg, hela rågkärnor och surdeg är brödingredienser fördelaktiga ur hälsosynpunkt. Detta, i kombination med positionen bröd har som baslivsmedel, gör det till ett potentiellt folkhälsoverktyg. Hälsosamma ingrediensmodifieringar kan dock innebära förändringar av smak och textur, något som konsumenterna kanske inte accepterar.

    Framgångsrik produktutveckling av hälsosamma livsmedel kräver därför god kännedom om hur hälsosamma komponenter påverkar livsmedlet sensoriskt, och vad detta har för effekt på konsumenternas gillande. För sådana ändamål är sensorisk analys mycket användbart.

    Denna studies syfte var att ta fram sensoriska profiler och information om konsumentacceptans för nio bröd; tre kommersiella portionsrågbröd, respektive två nya versioner av dessa vardera, modifierade genom tillägg av hela rågkärnor. Sekundärt var syftet att undersöka brödintag och vikten av hälsoaspekten vid brödval hos konsumenterna.

    Portionsbröden Rågkusar, Aktiv Råg och Rund & god modifierades genom  tillägg av hela rågkärnor i två olika nivåer. En sensorisk panel (n=13) togs fram (enligt ISO-standard) och tränades i profilbedömning under sju tillfällen à 2-3 h. Därefter bedömde panelen de nio brödens intensitet av elva sensoriska egenskaper, på en linjär, unipoöär skala (0-10), i två replikat. Dessutom utfördes ett konsumenttest (n=448), där bröden med hjälp av en enkät utvärderades på en niogradig gillandeskala. Enkäten innehöll även en fråga vardera om brödintag och vikten av hälsoaspekten vid brödval.

    Rågkusar, Aktiv Råg och Rund & god var signifikant skilda gällande de flesta sensoriska egenskaper. Rågkusar hade häg intensitet av kompakthet, lukt av rostade cerealier, syrlig lukt, syrlighet, sälta, beska och rågsmak, men var låga i saftighet, sirapslukt och sötma. Detta medan Akriv Råg och Rund & god båda var saftigare, sötare, högre i sirapslukt, lägre i syrlig lukt och lukt av rostade cerealier, kompakthet, hårdhet, syrlighet, sälta, beska och rågsmak. De sensoriska egenskaperna påverkades inte av rågkärnorna, med undantag för hårdhet, som var lägre i Aktiv Råg och Rund & god med den högre mängden kärnor, än i respektive originalbröd (p<0,05). Medelvärden för brödens gillande var mellan 5,29 och 6,46, Aktiv Råg och Rund & god var mer omtyckta än Rågkusar (p<0,05). Rågkärnorna hade ingen inverkan på gillandet (p>0,05). Konsumenterna åt i snitt tre skivor/bitar bröd per dag, och 95% av dem höll helt eller delvis med om att det var viktigt att brödet de oftast äter är nyttigt.

    Genom tillägg av hela rågkärnor i de undersökta mängderna, kan näringsinnehållet i rågbröd förbättras utan större påverkan på sensoriska egenskaper eller underminering av konsumetnacceptansen. Då konsumenter tycker att det är viktigt med hälsosamt bröd, är denna information användbar inte bara folkhälsomässigt, utan även för brödindustrin.

  • 252567.
    Örtoft, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Regulation of the GAP-43, C-SRC, HASH-1 and ID genes during neuronal differentiation of neuroblastoma cells1995Doctoral thesis, comprehensive summary (Other academic)
  • 252568.
    Örtquist, Frida
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Theology, Department of Theology.
    Can the Subaltern be heard?: A Discussion on ethical strategies for Communication in a Postcolonial World2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This thesis relies on the works of Gayatri Chakravorty Spivak and Seyla Benhabib in the field

    of Postcolonialism. Guided by their theoretical insights it is aiming at providing an

    understanding of how postcolonial structures within the International Humanitarian Aid

    discourse takes form and discuss strategies for communication that would be deemed

    justified in this context. Through a field research in Lebanon, focusing on the Lebanese Red

    Cross and their methods used for communication, it provides a scrutiny of the theoretical

    insights of Spivak and Benhabib, in order to see how plausible they are when discussing the

    way Global Humanitarian Organizations operate in todays’ world. In the conclusive

    discussion, the study exposes the importance for these organizations to let go of their

    essentialist way of looking at the subaltern, continuously depriving her of her subject

    position. In a context of asymmetrical power relations, there is a need for these organizations

    to ”learn to learn from below”. The people of the Western world need to unlearn Western

    privilege to enable themselves to relate to people and communities outside of their own

    paradigm and thus create presuppositions for an ethical communication.

  • 252569.
    Örtqvist, Anne K
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lundholm, Cecilia
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Fang, Fang
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Almqvist, Catarina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.; Unit of Pediatric Allergy and Pulmonology at Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Parental antibiotics and childhood asthma: a population-based study2017In: Journal of Allergy and Clinical Immunology: In Practice, ISSN 2213-2198, E-ISSN 2213-2201, Vol. 5, no 5, p. 1451-1454.e4, article id S2213-2198(17)30178-2Article in journal (Other academic)
    Abstract [en]

    In this population-based study on antibiotic treatment before, during, and after pregnancy, using paternal exposure as negative control, we confirm that associations between maternal antibiotic exposure and childhood asthma are partly explained by familial confounding such as genes and environment.

  • 252570. Örtqvist, Eva
    et al.
    Björk, Elisabeth
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Wallensteen, M
    Ludvigsson, Johnny
    Åman, Jan
    Johansson, Calle
    Forsander, Gun
    Lindgren, Fredrik
    Berglund, Lars
    Bengtsson, Mats
    Department of Oncology, Radiology and Clinical Immunology.
    Berne, Christian
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Persson, Bengt
    Karlsson, F Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Temporary preservation of beta-cell function by diazoxide treatment in childhood type 1 diabetes.2004In: Diabetes Care, ISSN 0149-5992, Vol. 27, no 9, p. 2191-7Article in journal (Refereed)
  • 252571.
    Örtqvist, Pernilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    On the Design and Synthesis of Hepatitis C Virus NS3 Protease Inhibitors: From Tripeptides to Achiral Compounds2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Infection by the hepatitis C virus (HCV) leads to inflammation of the liver, i.e. hepatitis. The acute infection often progresses to a chronic phase during which the liver function is gradually impaired. Approximately 20% of these chronic cases develop liver cirrhosis, with an ensuing increased risk of liver cancer. Global estimates of the total number of chronic cases range from 123–170 million. Yet, neither specific anti-HCV drugs nor vaccines are available. When drugs become available for daily clinical use, rapid development of drug-resistant strains is expected, making resistance an important issue.

    One of the most studied targets for specific anti-HCV drugs is the NS3 protease. The main objectives of the work presented in this thesis were to design and synthesise peptidomimetic inhibitors of this enzyme, and to establish the structure–activity relationships (SARs) regarding the inhibition of the wild type as well as of the known resistant variants A156T and D168V.

    Substituted prolines are common P2 residues in HCV NS3 protease inhibitors. To decrease the peptide character of the inhibitors, the non-coded phenylglycine was evaluated as a proline replacement in combination with known and novel P3 and P1 residues and P2 substituents. The results confirmed that phenylglycine is a promising P2 scaffold, with a possible π-stacking interaction with histidine 57 of the active site. However, to benefit from its full potential, additional optimisation is required.

    A 2(1H)-pyrazinone-based scaffold was introduced as P3 residue. Utilising the scope of the method developed for the pyrazinone scaffold synthesis, the phenylglycine side-chain was transferred to the scaffold. In combination with an aromatic P1 building-block, this design yielded achiral, peptidomimetic inhibitors, three times more potent than the tripeptide lead.

    The SARs for the inhibition of the resistant variants A156T and D168V were investigated for compounds based on either P2 proline or phenyl­glycine. It was concluded that the vulnerability of the inhibitors to alterations in the enzyme depends on the P2 and the P1 residue, not only on the P2 as previously suggested.

    These results provide important information for the design of a new generation of inhibitors with improved properties.

    List of papers
    1.
    The record could not be found. The reason may be that the record is no longer available or you may have typed in a wrong id in the address field.
    2. Structure-Activity Relationships of HCV NS3 Protease Inhibitors Evaluated on the Drug-Resistant Variants A156T and D168V
    Open this publication in new window or tab >>Structure-Activity Relationships of HCV NS3 Protease Inhibitors Evaluated on the Drug-Resistant Variants A156T and D168V
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Medicinal Chemistry
    Research subject
    Medicinal Chemistry
    Identifiers
    urn:nbn:se:uu:diva-111363 (URN)
    Available from: 2009-12-16 Created: 2009-12-11 Last updated: 2018-01-12
    3. A straightforward microwave method for rapid synthesis of N-1, C-6 functionalized 3,5-dichloro-2(1H)-pyrazinones
    Open this publication in new window or tab >>A straightforward microwave method for rapid synthesis of N-1, C-6 functionalized 3,5-dichloro-2(1H)-pyrazinones
    2009 (English)In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 7, no 13, p. 2809-2815Article in journal (Refereed) Published
    Abstract [en]

    A rapid and versatile one-pot, 2 * 10 min microwave protocol for the prepn. of N-1 and C-6 decorated 3,5-dichloro-2(1H)-pyrazinones, e.g., I, from the corresponding primary amines and aldehyde was developed. Comparable reaction sequences using classical conditions require about 1-2 days of heating. The alpha -aminonitrile was first generated in a Strecker reaction and thereafter cyclized under microwave heating. The microwave approach developed offers the possibility of efficiently generating and utilizing functionalized 3-amino-5-chloro-2(1H)-pyrazinone-N-1-carboxylic acids as beta -strand inducing core structures in a medicinal chem. context. To illustrate the usefulness of the method, the synthesis of two novel 2(1H)-pyrazinone-contg. Hepatitis C virus NS3 protease inhibitors, e.g., II, is reported.

    National Category
    Pharmaceutical Sciences
    Research subject
    Medicinal Chemistry; Organic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-110737 (URN)10.1039/b90550lk (DOI)000267124300020 ()
    Note

    CAN 151:245625 28-17 Heterocyclic Compounds (More Than One Hetero Atom) Journal 1477-0520 written in English. 1178896-10-0P; 1178896-11-1P Role: PAC (Pharmacological activity), SPN (Synthetic preparation), BIOL (Biological study), PREP (Preparation) (prepn. and hepatitis C virus NS3 protease inhibitory activity of (pyrazinylacetamido)cyclopropanoic acid derivs. via coupling reaction, hydrolysis, and peptide coupling of pyrazinylacetate deriv.); 4248-19-5 (tert-Butyl carbamate); 259214-56-7 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. and hepatitis C virus NS3 protease inhibitory activity of (pyrazinylacetamido)cyclopropanoic acid derivs. via coupling reaction, hydrolysis, and peptide coupling of pyrazinylacetate deriv.); 1178896-08-6P; 1178896-09-7P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. and hepatitis C virus NS3 protease inhibitory activity of (pyrazinylacetamido)cyclopropanoic acid derivs. via coupling reaction, hydrolysis, and peptide coupling of pyrazinylacetate deriv.); 62-53-3 (Aniline); 100-46-9 (Benzylamine); 100-52-7 (Benzaldehyde); 108-91-8 (Cyclohexylamine); 109-73-9 (1-Butanamine); 122-78-1 (Benzeneacetaldehyde); 1122-91-4 (4-Bromobenzaldehyde); 2393-23-9 (4-Methoxybenzylamine); 2462-31-9; 3009-97-0; 3010-04-6; 3081-24-1; 3132-99-8 (3-Bromobenzaldehyde); 3182-93-2; 21760-98-5; 37760-98-8 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of dichloropyrazinones via Strecker reaction of primary amines, aldehydes, and trimethylsilyl cyanide, followed by cyclocondensation with oxalyl chloride under microwave irradn.); 2182-39-0P; 252271-82-2P; 308845-80-9P; 1178896-02-0P; 1178896-07-5P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of dichloropyrazinones via Strecker reaction of primary amines, aldehydes, and trimethylsilyl cyanide, followed by cyclocondensation with oxalyl chloride under microwave irradn.); 87486-37-1P; 173200-35-6P; 173200-36-7P; 199296-26-9P; 308845-81-0P; 595581-85-4P; 602280-43-3P; 1178895-95-8P; 1178895-96-9P; 1178895-97-0P; 1178895-98-1P; 1178895-99-2P; 1178896-00-8P; 1178896-01-9P; 1178896-03-1P; 1178896-04-2P; 1178896-05-3P; 1178896-06-4P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of dichloropyrazinones via Strecker reaction of primary amines, aldehydes, and trimethylsilyl cyanide, followed by cyclocondensation with oxalyl chloride under microwave irradn.)

    Available from: 2009-11-24 Created: 2009-11-24 Last updated: 2018-01-12Bibliographically approved
    4. Discovery of Achiral Inhibitors of the Hepatitis C Virus NS3 Protease based on 2(1H)-pyrazinones
    Open this publication in new window or tab >>Discovery of Achiral Inhibitors of the Hepatitis C Virus NS3 Protease based on 2(1H)-pyrazinones
    Show others...
    2010 (English)In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 18, no 17, p. 6512-6525Article in journal (Refereed) Published
    Abstract [en]

    Herein, the design, synthesis and inhibitory potency of a series of novel hepatitis C virus (HCV) NS3 protease inhibitors are presented. These inhibitors are based on a 2(1H)-pyrazinone P3 scaffold in combination with either a P2 phenylglycine or a glycine, and they were evaluated on the wild type as well as on two resistant variants of the enzyme, A156T and D168V. Molecular modelling suggested that the aromatic side-chain of the P2 phenylglycine occupies the same space as the substituent in position 6 on the pyrazinone core. The versatile synthetic route applied for the pyrazinone synthesis made a switch between the two positions easily feasible, resulting in phenyl- or benzyl substituted pyrazinones and leaving glycine as the P2 residue. Of several P1-P1′ residues evaluated, an aromatic P1-P1′ scaffold was found superior in combination with the new P3-P2 building block. As a result, an entirely new type of achiral and rigidified inhibitors was discovered, with the best of the novel inhibitors having fourfold improved potency compared to the corresponding tripeptide lead. We consider these achiral inhibitors highly suitable as starting points for further optimization.

    Keywords
    Hepatitis C virus NS3 protease, Protease inhibitors, 2(1H)-pyrazinone, Phenylglycine
    National Category
    Medicinal Chemistry
    Research subject
    Medicinal Chemistry
    Identifiers
    urn:nbn:se:uu:diva-111366 (URN)10.1016/j.bmc.2010.06.101 (DOI)000281203300032 ()20673728 (PubMedID)
    Note

    Uppdaterad från manuskript till Artikel 20101206

    Available from: 2009-12-16 Created: 2009-12-11 Last updated: 2018-01-12Bibliographically approved
  • 252572.
    Örtqvist, Pernilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Gising, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Ehrenberg, Angelica
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Biochemistry.
    Vema, Aparna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Borg, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Karlén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Larhed, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Danielson, U. Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Biochemistry.
    Sandström, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Discovery of Achiral Inhibitors of the Hepatitis C Virus NS3 Protease based on 2(1H)-pyrazinones2010In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 18, no 17, p. 6512-6525Article in journal (Refereed)
    Abstract [en]

    Herein, the design, synthesis and inhibitory potency of a series of novel hepatitis C virus (HCV) NS3 protease inhibitors are presented. These inhibitors are based on a 2(1H)-pyrazinone P3 scaffold in combination with either a P2 phenylglycine or a glycine, and they were evaluated on the wild type as well as on two resistant variants of the enzyme, A156T and D168V. Molecular modelling suggested that the aromatic side-chain of the P2 phenylglycine occupies the same space as the substituent in position 6 on the pyrazinone core. The versatile synthetic route applied for the pyrazinone synthesis made a switch between the two positions easily feasible, resulting in phenyl- or benzyl substituted pyrazinones and leaving glycine as the P2 residue. Of several P1-P1′ residues evaluated, an aromatic P1-P1′ scaffold was found superior in combination with the new P3-P2 building block. As a result, an entirely new type of achiral and rigidified inhibitors was discovered, with the best of the novel inhibitors having fourfold improved potency compared to the corresponding tripeptide lead. We consider these achiral inhibitors highly suitable as starting points for further optimization.

  • 252573.
    Örtqvist, Pernilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Peterson, Shane D.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Åkerblom, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Gossas, Thomas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry.
    Sabnis, Yogesh A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Fransson, Rebecca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Lindeberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Danielson, U. Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry.
    Karlén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Sandström, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Phenylglycine as a Novel P2 Scaffold in Hepatitis C Virus NS3 Protease Inhibitors2007In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 15, no 3, p. 1448-1474Article in journal (Refereed)
    Abstract [en]

    Molecular modeling and inhibitory potencies of tetrapeptide protease inhibitors of HCV NS3 proposed phenylglycine as a new promising P2 residue. The results suggest that phenylglycine might be capable of interacting with the NS3 (protease-helicase/NTPase) in ways not possible for the common P2 proline-based inhibitors. Thus, a series of tripeptides, both linear and macrocyclic, based on p-hydroxy-phenylglycine in the P2 position were prepared and their inhibitory effect determined. When the p-hydroxy group was replaced by methoxy, isoquinolin-, or quinolinyloxy functions, inhibitors with improved potencies were obtained. The P2 phenylglycine-based inhibitors were further optimized by C-terminal extension to acyl sulfonamides and by P1–P3 cyclization, which gave products with inhibition constants in the nanomolar range (75 nM).

  • 252574.
    Örtqvist, Pernilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Vema, Aparna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Ehrenberg, Angelica
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Dahl, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Rönn, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Åkerblom, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Danielson, U. Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Sandström, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Structure-Activity Relationships of HCV NS3 Protease Inhibitors Evaluated on the Drug-Resistant Variants A156T and D168VManuscript (preprint) (Other academic)
  • 252575.
    Örtqvist, Pernilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Vema, Aparna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Ehrenberg, Angelica E
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Biochemistry.
    Dahl, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Biochemistry.
    Rönn, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Åkerblom, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Karlén, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Danielson, U Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Biochemistry.
    Sandström, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Structure-activity relationships of HCV NS3 protease inhibitors evaluated on the drug-resistant variants A156T and D168V2010In: Antiviral Therapy, ISSN 1359-6535, E-ISSN 2040-2058, Vol. 15, no 6, p. 841-852Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: HCV infections are a serious threat to public health. An important drug target is the NS3 protease, for which several inhibitors are in clinical trials. Because of the high mutation rate of the virus, resistance against any HCV-specific drug is likely to become a substantial problem. Structure-activity data for the major resistant variants are therefore needed to guide future designs of protease inhibitors. METHODS: The inhibitory potency of tripeptide NS3 protease inhibitors, with either a P2 proline or phenylglycine, in combination with different P3 and P1-P1' groups, was assessed in enzyme activity assays using the full-length NS3 protein with known resistance-conferring substitutions A156T or D168V. The results obtained from these variants were compared with the inhibition of the wild-type enzyme. Molecular modelling was used to rationalize the biochemical results. RESULTS: Inhibitors combining the P2 proline and P1 (1R,2S)-1-amino-2-vinylcyclopropyl-carboxylic acid (vinylACCA) lost much of their potency on the resistant variants. Exchange of the P2 proline for phenylglycine yielded inhibitors that were equipotent on the wild-type and on the A156T and D168V variants. The same result was obtained from the combination of either the P2 residue with a norvaline or an aromatic scaffold in the P1 position. CONCLUSIONS: The combination of a substituted P2 proline and P1 vinylACCA appears to be the main problem behind the observed resistance. Molecular modelling suggests an enforced change in binding conformation for the P2 proline-based inhibitors, whereas the phenylglycine-based inhibitors retained their wild-type binding conformation in the substituted forms of the enzyme.

  • 252576. Örtqvist, Åke
    et al.
    Holmberg, Hans
    Norman, Christer
    Cars, Otto
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Doxycyklin är ingen ­hostmedicin: Antibiotika vid akut bronkit är både onödigt och riskabelt2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 24-25, p. 1666-7Article in journal (Refereed)
  • 252577.
    Örvill, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Industrial Engineering & Management.
    Concept for battery change: Mining vehicles2018Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Epiroc Rock Drills AB in Örebro manufactures and develops machinery for the infrastructure required to maintain a fully operational mining industry, such as ventilation, drilling rigs, trucks and loaders etc.

    In these environmentally conscious times, a large market focus forzero emission machines has begun to emerge. By replacing today'sinternal combustion engines, mining companies can save large sums of money in ventilation costs and fuel while creating a more pleasant working environment in the mines. Due to these rapidly changing needs, Epiroc's machines must also change in design and performance. Epiroc has thus chosen to use interchangeable batteries in their new generation of mining machines. When the battery is discharged, it must be easy to replace with a fullycharged one. From an economic point of view, it is also important that the machine is always in production without any stops, making fast and efficient battery switches desirable. At present, the battery change is usually done with a mono-rail crane down the mine. This has proved to be very difficult and ineffective as the battery is too often jammed into the machine due to the fact that the machine is poorly positioned against the crane. Ceiling heightis also a problem, preferably one should have about 6-7 meters to accomplish a safe lift with the crane, which is not always possible down in a mine.

    In order to find a more long-term solution to this problem, this degree project took its start. During the course of the process, a number of methods in product development and concept generation have been used to develop different concepts and screen them based on the needs identified at the beginning of the work. The main problem was divided into four sub problems to facilitate conceptgeneration, the most promising sub concepts were visualized using CAD and then put together in different combinations. These combinations were then evaluated against today's solution to easily see what concept should be further developed.

    This resulted in a concept that consists of a separate platform,which can either be placed on a vehicle or as a stand-alone station. On this platform there are two telescopic arms, one on each side. These arms lifts the three ton heavy battery from the mining machine in an arcuate motion over a charged battery on the platform, placing it in a designated location and then lifts the charged battery into the machine. With this concept, it is also possible to accomplish a safe change with a limited ceiling height of approximately 3.5-4 meters, which is an improvement compared to today's solution.

  • 252578.
    Ösby, Eva Taube, Adam Cavallin-Ståhl, Eva Hagberg, Hans Björkholm, Magnus
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Information Science.
    Reproducibility of Tumor Response Evaluation in Patients with High-Grade Malignant non-Hodgkin´s Lymphoma2001In: Medical Oncology, Vol. 18, no 2, p. 137-140Article in journal (Refereed)
  • 252579.
    Össbo, Åsa
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of ALM.
    Spår av fragment ur minneskärvor. En studie kring bevarande av utställningsmaterial och -dokumentation2005Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 252580.
    Öst Gustafsson, Hampus
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Literature.
    Dikten i "den nya fredens värld": Litteraturdebatt i tidskriften Samtid och Framtid 1944–19492015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    This thesis analyses the literature debate in the overlooked Swedish magazine Samtid och Framtid 1944–1949. The magazine was first published at the end of World War II on the initiative of publisher Johan Hansson. After an interesting start, the terms of the debate in the magazine were changed after a power struggle on the editorial level. Thus, the magazine never became the influential arena for literary discussions that it first had potential of becoming. With its initial focus on how to construct a new post-war world, the debates in the magazine, however, provide an interesting material for an investigation of attempts to renegotiate the position of literature in society. This is conducted through a perspective that focuses on the debaters’ use of metaphors, but also their specific experiences of the past and their expectations on the future. Central oppositions between aesthetic and committed ideals are highlighted, but also between individualism and collectivism. It is also demonstrated that the debates successively turned more concrete, not least focusing on the very influential Swedish literary generation of the 1940s.

  • 252581.
    Öst, Lars-Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Mode of acquisition of phobias 1985Doctoral thesis, comprehensive summary (Other academic)
  • 252582. Öst, Lars-Göran
    et al.
    Westling, Bengt E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Psychiatry, University hospital.
    Appied relaxation vs cognitive behavior therapy in the treatment of panic disorder1995In: Behaviour Research and Therapy, ISSN 0005-7967, E-ISSN 1873-622X, Vol. 33, no 2, p. 145-158Article in journal (Refereed)
    Abstract [en]

    The present study investigated the efficacy of a coping-technique, applied relaxation (AR) and cognitive behavior therapy (CBT), in the treatment of panic disorder. Thirty-eight outpatients fulfilling the DSM-III-R criteria for panic disorder with no (n = 30) or mild (n = 8) avoidance were assessed with independent assessor ratings, self-report scales and self-observation of panic attacks before and after treatment, and at a 1-yr follow-up. The patients were treated individually for 12 weekly sessions. The results showed that both treatments yielded very large improvements, which were maintained, or furthered at follow-up. There was no difference between AR and CBT on any measure. The proportion of panic-free patients were 65 and 74% at post-treatment, and 82 and 89% at follow-up, for AR and CBT, respectively. There were no relapses at follow-up, on the contrary 55% of the patients who still had panic attacks at post-treatment were panic-free at follow-up. Besides affecting panic attacks the treatments also yielded marked and lasting changes on generalized anxiety, depression and cognitive misinterpretations. The conclusion that can be drawn is that both AR and CBT are effective treatments for panic disorder without avoidance.

  • 252583.
    Öst, Thomas
    Uppsala University, Units outside the University, Institute for Housing and Urban Research.
    Ecological Modernisation vs. Ecocentrism? On Controversial Views regarding Strategies for Attaining Ecological Sustainability2002In: Sustainable Building 2002. 3rd International Conference on Sustainable Building. 23-25 September 2002. Oslo, Norway, 2002Conference paper (Other scientific)
  • 252584.
    Öst, Thomas
    Uppsala University, Units outside the University, Institute for Housing and Urban Research.
    Ekologisk modernisering och djupekologi. Två olika strategier för ekologisk hållbarhet (Ecological modernisation and deep green ecology. Two different strategies for ecological sustainability)2003In: Västra Hamnen Bo01 – Framtidsstaden. En utvärdering, Göteborg: Chalmers Tekniska Högskola , 2003, p. 135-154Chapter in book (Other scientific)
  • 252585.
    Öst, Thomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Institute for Housing and Urban Research.
    Ekologisk stadsdel för (o)intresserade invånare?2005In: Bo01 - Hållbar framtidsstad: Lärdomar och erfarenheter, Stockholm: Formas , 2005, p. 81-90Chapter in book (Other (popular science, discussion, etc.))
    Abstract [en]

    De boende i Västra Hamnen i Malmö utgör i vissa avseenden en speciell befolkningsgrupp. De är yngre och mer välutbildade än genomsnittssvensken och sannolikt också mer välbeställda. Deras miljöengagemang är däremot ganska klent. Byggherrarna hade rätt då de byggde för välbetalda och karriärinriktade människor.

  • 252586.
    Öst, Thomas
    Uppsala University, Units outside the University, Institute for Housing and Urban Research.
    Heading for Ecological Sustainability in Swedish Urban Areas. Visions, Measures and Potential Problems2003Conference paper (Other scientific)
  • 252587.
    Öst, Thomas
    Uppsala University, University Administration, Planning Division.
    Internationella masterprogram vid Uppsala universitet: En kvalitativ studie av studenters och lärares erfarenheter2012Report (Other academic)
  • 252588.
    Öst, Thomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Sociology. Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Institute for Housing and Urban Research.
    Livsstilsförändringar och "grön" teknik: Om relationen mellan ekonomisk och ekologisk rationalitet i miljöpolitiken2007Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This dissertation is a study on the contemporary environmental policy discourse called ecological modernisation and especially on eco-modernist social theory. Its central tenet on the (forthcoming) simultaneous existence of economic rationality and ecological rationality constitutes the primary object of an ‘explanatory critique’. The twofold aim of the study is (1) to show that the idea of individuals simultaneously being both ecologically and economically rational must be false and (2) to suggest one reason for its existence. Hence, the simultaneity motif within ecological modernisation theory is analysed as an example of ‘false consciousness’.

    By presenting certain energy saving measures as examples, the environmental planning dilemma inherent in the practice of simultaneously applying ‘green’ technological measures and encouraging ‘green’ lifestyle changes is demonstrated. ‘Green’ technology is in the study described as a type of economic means of control and thus permeated by economic rationality while, on the contrary, ‘green’ lifestyle changes are described as genuinely representing ecological rationality. The study contends that you cannot evoke ecological values (essential for the emergence of ‘green’ lifestyles) by applying economic means of control. Drawing on the analytic dualism of critical realist Margaret S. Archer and the neo-Marxist environmental sociology of Allan Schnaiberg, this dilemma is conceived of as a ‘constraining contradiction’ or a ‘dialectical conflict’.

    The study ends with a tentative synthesis of ecological modernisation and ‘green rationalism’ – the latter being political scientist John S. Dryzek’s term for the neo-Marxist environmental policy discourse. It is argued that ecological values could co-exist with economic objectives, but only insofar the ecologically rational activities and the economically rational activities in society are kept apart and, consequently, do not conflict. If then the ecologically rational actions eventually become more numerous than the economically rational ones, a truly ecological rationalisation of society might ensue.

  • 252589.
    Öst, Thomas
    Uppsala University, Units outside the University, Institute for Housing and Urban Research.
    Review of: Paul Balchin and Maureen Rhoden (2002) Housing Policy. An Introduction (4th edition). London and New York: Routledge. 492 pp. ISBN: 0 415 25214 8 (pbk)2003In: Housing, Theory and Society, Vol. 20, no 1, p. 55-56Article, book review (Other scientific)
  • 252590.
    Öst, Thomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Institute for Housing and Urban Research.
    Sustainable urban district for (un)interested residents?2005In: Sustainable City of Tomorrow: Bo01 - Experiences of a Swedish Housing Exposition, Stockholm: Formas , 2005, p. 81-90Chapter in book (Other (popular science, discussion, etc.))
    Abstract [en]

    In some respects the residents of Malmö's Western Harbour are a community apart. They are younger and better-educated than the average Swede and probably also better off. Their environmental interest, though, is pretty limited. In building for well-paid careerists, the developers were on target.

  • 252591.
    Öst, Thomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Institute for Housing and Urban Research.
    The 'Green' Technology-Lifestyle Change Dialectic.: On the Possibility of an Ecologically Rational Growth2007Conference paper (Other (popular science, discussion, etc.))
  • 252592.
    Öst, Thomas
    et al.
    Uppsala University, Units outside the University, Institute for Housing and Urban Research.
    Sandstedt, Eva
    Diskussion: Västra Hamnen – Ett led i den hållbara utvecklingen? (Discussion: The Western Harbour – A stage in the sustainable development?)2003In: Västra Hamnen Bo01 – Framtidsstaden. En utvärdering, 2003, p. 161-166Chapter in book (Other scientific)
  • 252593.
    Öst, Thomas
    et al.
    Uppsala University, Units outside the University, Institute for Housing and Urban Research.
    Sandström, Greger
    Livsstil och energihushållning. En essä om teknikens landvinningar och brukares attityder (Life style and energy savings. An essay on technological innovations and users' attitudes)2002In: Energi- och resurshushållning i bebyggelse (Energy and Resource Savings in Built Environment), , p. 54-81Report (Other scientific)
  • 252594.
    Östangård, Louise
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Reactivity Analysis of Nuclear Fuel Storages: The Effect of 238U Nuclear Data Uncertainties2013Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The aim of this master thesis work was to investigate how the uncertainties in nuclear data for 238U affects the uncertainty of keff in criticality simulations for nuclear fuel storages. This was performed by using the Total Monte Carlo (TMC) method which allows propagation of nuclear data uncertainties from basic nuclear physics to reactor parameters, such as keff. The TMC approach relies on simulations with hundreds of calculations of keff with different random nuclear data libraries for 238U for each calculation. The result is a probability distribution for keff where the standard deviation for the distribution represents a spread in keff due to statistical and nuclear data uncertainties.

    Simulations were performed with MCNP for a nuclear fuel storage representing two different cases:  Normal Case and Worst Case. Normal Case represents a scenario during normal conditions and Worst Case represents accident conditions where optimal moderation occurs. In order to validate the MCNP calculations and the libraries produced with TMC, criticality benchmarks were used.

    The calculated mean value of keff for the criticality benchmark simulations with random libraries produced with TMC obtained a good agreement with the experimental keff for the benchmarks. This indicates that the libraries used in this this work were of good quality.

    The TMC method´s drawback is the long calculation time, therefore the new method, fast TMC, was tested.  Both fast TMC and original TMC were applied to the Normal Case. The two methods obtained similar results, indicating that fast TMC is a good option in order to reduce the computational time. The computer time using fast TMC was found to be significantly faster compared with original TMC in this work.

    The 238U nuclear data uncertainty was obtained to be 209 pcm for the Normal Case, both for original and fast TMC. For the Worst Case simulation the 238U nuclear data uncertainty was obtained to be 672 pcm with fast TMC. These results show the importance of handling uncertainties in nuclear data in order to improve the knowledge about the uncertainties for criticality calculations of keff

  • 252595.
    Östberg, Catrine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Herlitz, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Hur sömnproblem hos små barn hanteras av barnhälsovårdssköterskor i Region Uppsala2018Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Sleeping-problems are common among small children and affect the lives of the whole family. Support for the parents is an important part of the Child-Health-Services (CHS). The advices should be evidence-based and equal.

    Objective:  The purpose with this study was to explore how sleep-problems among children are treated by the CHS-nurses in the Uppsala county.

    Method: A qualitative study with semi-structured interviews were practiced. Nine CHS-nurses were interviewed. The interviews were audio-recorded, transcribed verbatim and analyzed with content analysis. Dorothea Orem's self-care model was chosen as the theoretical framework.

    Results: Three categories of how CHS-nurses’ treated sleep-problem were identified: CHS-nurses way of working is multifaceted, Flexibility and individual adaption is necessary to cover the family’s needs, Sleep-advice is challenging but stimulating. The interviewed CHS-nurses dealt with sleeping-problems among small children in similar ways and were supported by the advice and routines in Rikshandboken. Almost all the CHS-nurses found it stimulating to work with sleep-advice. What limited the CHS-nurses in their work was the lack of time, both their own and the parents.

    Conclusion: To have an evidence-based and equal child health care the CHS-nurses play an important role when supporting families with children with sleep-problems. The CHC-nurses experienced that sleeping-problems among small children have increased, but the lack of time for the parents as well as the nurses is limiting the nurses in their work with sleep. It’s important that the advices that comes from the CHC-nurses are family-adapted.

  • 252596.
    Östberg, Ellen
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Business Studies.
    Martínez Bergström, Katarina
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Business Studies.
    Att motivera till säkert arbete: Motivation och målsättningsteori i en ny kontext2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Motstridiga mål och människans medvetna eller omedvetna strävan efter bekvämlighet kan leda till problem när företag vill motivera sina medarbetare till att arbeta mot organisationens mål. I ett företag där arbetsmiljön präglas av stora säkerhetsrisker är chefers förmåga att motivera till arbete i enlighet med företagets säkerhetsmål avgörande. En bransch som ofta sammankopplas med säkerhetsrisker är gruvbranschen. Syftet med denna studie är att förklara hur chefer inom ett gruvföretag motiverar sina medarbetare i gruvan att arbeta i enlighet med företagets säkerhetsmål. Studien har en deduktiv ansats där målsättningsteorin används som utgångspunkt. Datainsamlingen utgörs av semistrukturerade intervjuer med personer verksamma på olika befattningsnivåer inom gruvföretaget med den gemensamma nämnaren chefsposition. Studien visar att målsättningsteorin är en fruktbar teoretisk utgångspunkt och att den motivation som målsättning kan ge upphov till skapar möjlighet för chefer att påverka riktning, intensitet och uthållighet i gruvarbetarnas ansträngning. Vidare har tre begreppspar utmärkande för chefernas arbete kunnat urskiljas: generella och specifika metoder, proaktiva och reaktiva medel samt gruppen och individen som mottagare.

  • 252597.
    Östberg, Erland
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Pulmonary Atelectasis in General Anaesthesia: Clinical Studies on the Counteracting Effects of Positive End-Expiratory Pressure2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Partial lung collapse, i.e., pulmonary atelectasis, is common during general anaesthesia. The main causal mechanism is reduced lung volume with airway closure and subsequent gas absorption from preoxygenated alveoli. Atelectasis impairs oxygenation and forms the pathophysiological basis for postoperative pulmonary complications. Positive end-expiratory pressure (PEEP) counteracts the loss in lung volume, but its role in preventing atelectasis during anaesthesia is not clear.

    All studies included in this thesis were prospective randomized clinical trials. In the first study, oxygenation was used as a surrogate measure of atelectasis in obese patients undergoing laparoscopic gastric bypass. The subsequent studies used single-slice computed tomography (CT) to evaluate atelectasis in healthy patients undergoing non-abdominal surgery.

    Paper I: We studied the use of continuous positive airway pressure (CPAP) and PEEP during induction of anaesthesia and a reduced inspired oxygen fraction (FiO2) during emergence. Oxygenation was maintained in the group that received CPAP during induction, followed by a PEEP of 10 cmH2O. Postoperative oxygenation was impaired in the group that received a high FiO2 during emergence.

    Paper II: An early oxygen washout manoeuvre to quickly restore nitrogen levels and thus stabilize the alveoli, had no effect on atelectasis at the end of surgery. Both study groups exhibited small atelectasis after being ventilated with a moderate PEEP of 6-8 cmH2O during anaesthesia.

    Paper III: The effect of PEEP versus zero PEEP on atelectasis formation and oxygenation at the end of surgery was compared. The PEEP group maintained oxygenation better and exhibited less atelectasis than the zero-PEEP group, with atelectasis involving a median 1.8% of total lung area compared with 4.6% in the zero-PEEP group (P = 0.002).

    Paper IV: Postoperative atelectasis was compared between a group in which PEEP was maintained during emergence preoxygenation with FiO2 1.0 and a group in which PEEP was withdrawn just before the start of emergence preoxygenation with FiO2 1.0. The two groups had small atelectasis when fully awake at 30 min after extubation, with no statistically significant difference between them.  

    In conclusion, preserved end-expiratory lung volume is the key to avoiding atelectasis, in particular when an increased oxygen reserve is required during airway manipulation. PEEP is both necessary and sufficient to minimize atelectasis in healthy patients undergoing non-abdominal surgery.

    List of papers
    1. Preserved oxygenation in obese patients receiving protective ventilation during laparoscopic surgery: a randomized controlled study
    Open this publication in new window or tab >>Preserved oxygenation in obese patients receiving protective ventilation during laparoscopic surgery: a randomized controlled study
    Show others...
    2016 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 1, p. 26-35Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Venous admixture from atelectasis and airway closure impedes oxygenation during general anaesthesia. We tested the hypothesis that continuous positive airway pressure (CPAP) during pre-oxygenation and reduced fraction of inspiratory oxygen (FIO2 ) during emergence from anaesthesia can improve oxygenation in patients with obesity undergoing laparoscopic surgery.

    METHODS: In the intervention group (n = 20, median BMI 41.9), a CPAP of 10 cmH2 O was used during pre-oxygenation and induction of anaesthesia, but no CPAP was used in the control group (n = 20, median BMI 38.1). During anaesthesia, all patients were ventilated in volume-controlled mode with an FIO2 of 0.4 and a positive end-expiratory pressure (PEEP) of 10 cmH2 O. During emergence, before extubation, the control group was given an FIO2 of 1.0 and the intervention group was divided into two subgroups, which were given an FIO2 of 1.0 or 0.31. Oxygenation was assessed perioperatively by the estimated venous admixture (EVA).

    RESULTS: The median EVA before pre-oxygenation was about 8% in both groups. During anaesthesia after intubation, the median EVA was 8.2% in the intervention vs. 13.2% in the control group (P = 0.048). After CO2 pneumoperitoneum, the median EVA was 8.4% in the intervention vs. 9.9% in the control group (P > 0.05). One hour post-operatively, oxygenation had deteriorated in patients given an FIO2 of 1.0 during emergence but not in patients given an FIO2 of 0.31.

    CONCLUSIONS: A CPAP of 10 cmH2 O during pre-oxygenation and induction, followed by PEEP after intubation, seemed to preserve oxygenation during anaesthesia. Post-operative oxygenation depended on the FIO2 used during emergence.

    National Category
    Anesthesiology and Intensive Care
    Research subject
    Physiology; Anaesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-264212 (URN)10.1111/aas.12588 (DOI)000368139400005 ()26235391 (PubMedID)
    Available from: 2015-10-07 Created: 2015-10-07 Last updated: 2019-04-08
    2. Minimizing atelectasis formation during general anaesthesia-oxygen washout is a non-essential supplement to PEEP
    Open this publication in new window or tab >>Minimizing atelectasis formation during general anaesthesia-oxygen washout is a non-essential supplement to PEEP
    Show others...
    2017 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 2, p. 92-98Article in journal (Refereed) Published
    Abstract [en]

    Background: Following preoxygenation and induction of anaesthesia, most patients develop atelectasis. We hypothesized that an immediate restoration to a low oxygen level in the alveoli would prevent atelectasis formation and improve oxygenation during the ensuing anaesthesia. Methods: We randomly assigned 24 patients to either a control group (n=12) or an intervention group (n=12) receiving an oxygen washout procedure directly after intubation. Both groups were, depending on body mass index, ventilated with a positive end-expiratory pressure (PEEP) of 6-8 cmH(2)O during surgery. The atelectasis area was studied by computed tomography before emergence. Oxygenation levels were evaluated by measuring blood gases and calculating estimated venous admixture (EVA). Results: The atelectasis areas expressed as percentages of the total lung area were 2.0 (1.5-2.7) (median [interquartile range]) and 1.8 (1.4-3.3) in the intervention and control groups, respectively. The difference was non-significant, and also oxygenation was similar between the two groups. Compared to oxygenation before the start of anaesthesia, oxygenation at the end of surgery was improved in the intervention group, mean (SD) EVA from 7.6% (6.6%) to 3.9% (2.9%) (P=.019) and preserved in the control group, mean (SD) EVA from 5.0% (5.3%) to 5.6% (7.1%) (P=.59). .Conclusion: Although the oxygen washout restored a low pulmonary oxygen level within minutes, it did not further reduce atelectasis size. Both study groups had small atelectasis and good oxygenation. These results suggest that a moderate PEEP alone is sufficient to minimize atelectasis and maintain oxygenation in healthy patients.

    Place, publisher, year, edition, pages
    TAYLOR & FRANCIS LTD, 2017
    Keywords
    Atelectasis, computed tomography, general anaesthesia, oxygenation, PEEP, protective ventilation, ventilator settings
    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-323496 (URN)10.1080/03009734.2017.1294635 (DOI)000401756500004 ()28434271 (PubMedID)
    Available from: 2017-06-22 Created: 2017-06-22 Last updated: 2019-04-08Bibliographically approved
    3. Positive End-expiratory Pressure Alone Minimizes Atelectasis Formation in Nonabdominal Surgery: A Randomized Controlled Trial
    Open this publication in new window or tab >>Positive End-expiratory Pressure Alone Minimizes Atelectasis Formation in Nonabdominal Surgery: A Randomized Controlled Trial
    Show others...
    2018 (English)In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 128, no 6, p. 1117-1124Article in journal (Refereed) Published
    Abstract [en]

    Background: Various methods for protective ventilation are increasingly being recommended for patients undergoing general anesthesia. However, the importance of each individual component is still unclear. In particular, the perioperative use of positive end-expiratory pressure (PEEP) remains controversial. The authors tested the hypothesis that PEEP alone would be sufficient to limit atelectasis formation during nonabdominal surgery. Methods: This was a randomized controlled evaluator-blinded study. Twenty-four healthy patients undergoing general anesthesia were randomized to receive either mechanical ventilation with PEEP 7 or 9 cm H2O depending on body mass index (n = 12) or zero PEEP (n =12). No recruitment maneuvers were used. Hie primary outcome was atelectasis area as studied by computed tomography in a transverse scan near the diaphragm, at the end of surgery, before emergence. Oxygenation was evaluated by measuring blood gases and calculating the ratio of arterial oxygen partial pressure to inspired oxygen fraction (Pao(2)/Fio(2) ratio). Results: At the end of surgery, the median (range) atelectasis area, expressed as percentage of the total lung area, was 1.8 (0.3 to 9.9) in the PEEP group and 4.6 (1.0 to 10.2) in the zero PEEP group. Tire difference in medians was 2.8% (95% CI, 1.7 to 5.7%; A = 0.002). Oxygenation and carbon dioxide elimination were maintained in the PEEP group, but both deteriorated in the zero PEEP group. Conclusions: During nonabdominal surgery, adequate PEEP is sufficient to minimize atelectasis in healthy lungs and thereby maintain oxygenation. Titus, routine recruitment maneuvers seem unnecessary, and the authors suggest that they should only be utilized when clearly indicated.

    Place, publisher, year, edition, pages
    LIPPINCOTT WILLIAMS & WILKINS, 2018
    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-363070 (URN)10.1097/ALN.0000000000002134 (DOI)000441172900012 ()29462011 (PubMedID)
    Available from: 2018-10-12 Created: 2018-10-12 Last updated: 2019-04-08Bibliographically approved
    4. Positive end-expiratory pressure and postoperative atelectasis: A randomized controlled trial
    Open this publication in new window or tab >>Positive end-expiratory pressure and postoperative atelectasis: A randomized controlled trial
    Show others...
    2019 (English)In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175Article in journal (Refereed) In press
    Abstract [en]

    Background

    Positive end-expiratory pressure (PEEP) increases lung volume and protects against alveolar collapse during anesthesia. During emergence, safety preoxygenation preparatory to extubation makes the lung susceptible to gas absorption and alveolar collapse, especially in dependent regions being kept open by PEEP. We hypothesized that withdrawing PEEP before starting emergence preoxygenation would limit postoperative atelectasis formation.

    Methods

    This was a randomized controlled evaluator-blinded trial in 30 healthy patients undergoing non-abdominal surgery under general anesthesia and mechanical ventilation with PEEP 7 or 9 cm H2O depending on body mass index. A computed tomography scan at the end of surgery assessed baseline atelectasis. The study subjects were thereafter allocated to either maintained PEEP (n = 16) or zero PEEP (n = 14) during emergence preoxygenation. The primary outcome was change in atelectasis area as evaluated by a second computed tomography scan 30 min after extubation. Oxygenation was assessed by arterial blood gases.

    Results

    Baseline atelectasis was small and increased modestly during awakening, with no statistically significant difference between groups. With PEEP applied during awakening, the increase in atelectasis area was median (range) 1.6 (-1.1 to 12.3) cm2 and without PEEP 2.3 (-1.6 to 7.8) cm2. The difference was 0.7 cm2 (95% CI, -0.8 to 2.9 cm2; P = 0.400). Postoperative atelectasis for all patients was median 5.2 cm2 (95% CI, 4.3 to 5.7 cm2), corresponding to median 2.5% of the total lung area (95% CI, 2.0 to 3.0%). Postoperative oxygenation was unchanged in both groups when compared to oxygenation in the preoperative awake state.

    Conclusion

    Withdrawing PEEP before emergence preoxygenation does not reduce atelectasis formation after non-abdominal surgery. Despite using 100% O2 during awakening, postoperative atelectasis is small and does not affect oxygenation, possibly conditional on an open lung during anesthesia, as achieved by intraoperative PEEP.

    National Category
    Anesthesiology and Intensive Care
    Research subject
    Anaesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-381346 (URN)
    Available from: 2019-04-08 Created: 2019-04-08 Last updated: 2019-04-08
  • 252598.
    Östberg, Erland
    et al.
    Västerås & Koping Hosp, Dept Anaesthesia & Intens Care, Västerås, Sweden..
    Auner, Udo
    Vasteras Hosp, Dept Radiol, Västerås, Sweden..
    Enlund, Mats
    Clin Res Ctr, Västerås, Sweden..
    Zetterström, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Edmark, Lennart
    Västeras & Koping Hosp, Dept Anaesthesia & Intens Care, Västerås, Sweden..
    Minimizing atelectasis formation during general anaesthesia-oxygen washout is a non-essential supplement to PEEP2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 2, p. 92-98Article in journal (Refereed)
    Abstract [en]

    Background: Following preoxygenation and induction of anaesthesia, most patients develop atelectasis. We hypothesized that an immediate restoration to a low oxygen level in the alveoli would prevent atelectasis formation and improve oxygenation during the ensuing anaesthesia. Methods: We randomly assigned 24 patients to either a control group (n=12) or an intervention group (n=12) receiving an oxygen washout procedure directly after intubation. Both groups were, depending on body mass index, ventilated with a positive end-expiratory pressure (PEEP) of 6-8 cmH(2)O during surgery. The atelectasis area was studied by computed tomography before emergence. Oxygenation levels were evaluated by measuring blood gases and calculating estimated venous admixture (EVA). Results: The atelectasis areas expressed as percentages of the total lung area were 2.0 (1.5-2.7) (median [interquartile range]) and 1.8 (1.4-3.3) in the intervention and control groups, respectively. The difference was non-significant, and also oxygenation was similar between the two groups. Compared to oxygenation before the start of anaesthesia, oxygenation at the end of surgery was improved in the intervention group, mean (SD) EVA from 7.6% (6.6%) to 3.9% (2.9%) (P=.019) and preserved in the control group, mean (SD) EVA from 5.0% (5.3%) to 5.6% (7.1%) (P=.59). .Conclusion: Although the oxygen washout restored a low pulmonary oxygen level within minutes, it did not further reduce atelectasis size. Both study groups had small atelectasis and good oxygenation. These results suggest that a moderate PEEP alone is sufficient to minimize atelectasis and maintain oxygenation in healthy patients.

  • 252599.
    Östberg, Erland
    et al.
    Västerås & Köping Hosp, Dept Anesthesia & Intens Care, Västerås, Sweden.
    Thorisson, Arnar
    Västerås & Köping Hosp, Dept Radiol, Västerås, Sweden.
    Enlund, Mats
    Clin Res Ctr, Västerås, Sweden.
    Zetterström, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Edmark, Lennart
    Västerås & Köping Hosp, Dept Anesthesia & Intens Care, Västerås, Sweden.
    Positive End-expiratory Pressure Alone Minimizes Atelectasis Formation in Nonabdominal Surgery: A Randomized Controlled Trial2018In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 128, no 6, p. 1117-1124Article in journal (Refereed)
    Abstract [en]

    Background: Various methods for protective ventilation are increasingly being recommended for patients undergoing general anesthesia. However, the importance of each individual component is still unclear. In particular, the perioperative use of positive end-expiratory pressure (PEEP) remains controversial. The authors tested the hypothesis that PEEP alone would be sufficient to limit atelectasis formation during nonabdominal surgery. Methods: This was a randomized controlled evaluator-blinded study. Twenty-four healthy patients undergoing general anesthesia were randomized to receive either mechanical ventilation with PEEP 7 or 9 cm H2O depending on body mass index (n = 12) or zero PEEP (n =12). No recruitment maneuvers were used. Hie primary outcome was atelectasis area as studied by computed tomography in a transverse scan near the diaphragm, at the end of surgery, before emergence. Oxygenation was evaluated by measuring blood gases and calculating the ratio of arterial oxygen partial pressure to inspired oxygen fraction (Pao(2)/Fio(2) ratio). Results: At the end of surgery, the median (range) atelectasis area, expressed as percentage of the total lung area, was 1.8 (0.3 to 9.9) in the PEEP group and 4.6 (1.0 to 10.2) in the zero PEEP group. Tire difference in medians was 2.8% (95% CI, 1.7 to 5.7%; A = 0.002). Oxygenation and carbon dioxide elimination were maintained in the PEEP group, but both deteriorated in the zero PEEP group. Conclusions: During nonabdominal surgery, adequate PEEP is sufficient to minimize atelectasis in healthy lungs and thereby maintain oxygenation. Titus, routine recruitment maneuvers seem unnecessary, and the authors suggest that they should only be utilized when clearly indicated.

  • 252600.
    Östberg, Erland
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Thorisson, Arnar
    Enlund, Mats
    Zetterström, Henrik
    Hedenstierna, Göran
    Edmark, Lennart
    Positive end-expiratory pressure and postoperative atelectasis: A randomized controlled trial2019In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175Article in journal (Refereed)
    Abstract [en]

    Background

    Positive end-expiratory pressure (PEEP) increases lung volume and protects against alveolar collapse during anesthesia. During emergence, safety preoxygenation preparatory to extubation makes the lung susceptible to gas absorption and alveolar collapse, especially in dependent regions being kept open by PEEP. We hypothesized that withdrawing PEEP before starting emergence preoxygenation would limit postoperative atelectasis formation.

    Methods

    This was a randomized controlled evaluator-blinded trial in 30 healthy patients undergoing non-abdominal surgery under general anesthesia and mechanical ventilation with PEEP 7 or 9 cm H2O depending on body mass index. A computed tomography scan at the end of surgery assessed baseline atelectasis. The study subjects were thereafter allocated to either maintained PEEP (n = 16) or zero PEEP (n = 14) during emergence preoxygenation. The primary outcome was change in atelectasis area as evaluated by a second computed tomography scan 30 min after extubation. Oxygenation was assessed by arterial blood gases.

    Results

    Baseline atelectasis was small and increased modestly during awakening, with no statistically significant difference between groups. With PEEP applied during awakening, the increase in atelectasis area was median (range) 1.6 (-1.1 to 12.3) cm2 and without PEEP 2.3 (-1.6 to 7.8) cm2. The difference was 0.7 cm2 (95% CI, -0.8 to 2.9 cm2; P = 0.400). Postoperative atelectasis for all patients was median 5.2 cm2 (95% CI, 4.3 to 5.7 cm2), corresponding to median 2.5% of the total lung area (95% CI, 2.0 to 3.0%). Postoperative oxygenation was unchanged in both groups when compared to oxygenation in the preoperative awake state.

    Conclusion

    Withdrawing PEEP before emergence preoxygenation does not reduce atelectasis formation after non-abdominal surgery. Despite using 100% O2 during awakening, postoperative atelectasis is small and does not affect oxygenation, possibly conditional on an open lung during anesthesia, as achieved by intraoperative PEEP.

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