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  • 1.
    A Hulten, Maj
    et al.
    University Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands England .
    Patel, Suketu
    University Warwick, Department Biol Science, Coventry CV4 7AL, W Midlands England .
    Jonasson, Jon
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Iwarsson, Erik
    Karolinska University Hospital, Karolinska Institute, Department Mol Med and Surg, Clin Genet Unit, S-17176 Stockholm, Sweden .
    On the origin of the maternal age effect in trisomy 21 Down syndrome: the Oocyte Mosaicism Selection model2010In: Reproduction, ISSN 1470-1626, Vol. 139, no 1, 1-9 p.Article, review/survey (Refereed)
    Abstract [en]

    We have recently documented that trisomy 21 mosaicism is common in human foetal ovaries. On the basis of this observation we propose that the maternal age effect in Down syndrome (DS) is caused by the differential behaviour of trisomy 21 in relation to disomy 21 oocytes during development from foetal life until ovulation in adulthood. in particular, we suggest that trisomy 21 oocytes, lagging behind those that are disomic, may escape the timed pruning of the seven million in foetal life to the 300-400 finally selected for ovulation. The net effect of this preferential elimination will be an accumulation of trisomy 21 oocytes in the ovarian reserve of older women. We here highlight the implications of this Oocyte Mosaicism Selection (OMS) model with respect to the prevalent view that the maternal age effect is complex, dependent on many different biological and environmental factors. We examine conclusions drawn from recent large-scale studies in families, tracing DNA markers along the length of chromosome 21q between parents and DS children, in comparison to the OMS model. We conclude that these family linkage data are equally compatible with the maternal age effect originating from the accumulation of trisomy 21 oocytes with advancing maternal age. One relatively straightforward way to get to grips with what is actually going on in this regard would be to compare incidence of trisomy 21 oocytes (and their pairing configurations) in foetal ovaries with that in oocytes at the meiosis I stage from adult women.

  • 2. A Molarius, A
    et al.
    Granström, F
    Feldman, Inna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kalander Blomqvist, M
    Pettersson, H
    Ello, S
    Can financial insecurity and condescending treatment explain the higher prevalence of poor self-rated health in women than in men? A population-based cross-sectional study in Sweden2012Conference paper (Other academic)
  • 3.
    Aaby, Jacqueline
    et al.
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science.
    Ekblom, Jakob
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science.
    Hur blev det med hälsan?: En kvalitativ studie om elevers syn på hälsa i ämnet Idrott och hälsa i årskurs nio.2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Syftet med denna studie är att undersöka vilken uppfattning elever i årskurs nio har om hälsa. Ämnet Idrott och hälsa bedrivs på olika sätt och syftet med studien är även att få en klarare bild över hur eleverna upplever att de arbetar med hälsa i undervisningen. Genom intervjuer vill vi höra elevernas tankar och erfarenheter om hälsa och vad de skulle vilja lära sig mer om. Vi vill även veta vad de tycker är viktigt för att kunna påverka sin framtida hälsa.

  • 4.
    Aaby Orellana, Tanja
    et al.
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Nursing Science.
    Kirkegaard, Betina
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Nursing Science.
    Sjuksköterskors upplevelser av att implementera personcentrerad omvårdnad i slutenvården: -         En Empirisk Studie2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Person-centred care (PCC) is when the person seeking care get’s involved in their care and are seen as more then their illness or ailment. PCC as a concept began in dementia care, but is now the approach that most healthcare institutions strive after. To achieve the improved care that PCC can bring, there is need for a well- planned and clear implementation plan from the management.

    Aim: To describe the nursing staffs experience of implementing person-centred care as a work procedure in inpatient care.

    Method: An inductive qualitative study where eleven interviews was completed. Eight interviews were strategically chosen and a content analysis was carried out.

    Result: There is hope among the participants that implementation will bring a better and safer care, but also concerns about fear of change among the healthcare staff and increased workloads. Participants experience that PCC will place higher demans on the healthcare staff, especially nurses, regarding time, knowledge and communication skills.

    Conclusion: To provide the best care, there has to be dedicated and competent staff who also have the support and understanding from the management. Despite the obstacles that seem to exist, there is a positive spirit among the nurses in relation to the implementation of person-centred care.  There is hope that person-centred care, among other things, will increase participation that could lead to shorter hospital stays and risk of needing to seek care again short after being discharged from the hospital. Ultimately it provides a better care in the whole for the individual person seeking care.

  • 5.
    Aadland, Lena
    et al.
    University West, Department of Nursing, Health and Culture, Divison of Caring Sciences, undergraduate level.
    Ekelund, Anna-Karin
    University West, Department of Nursing, Health and Culture, Divison of Caring Sciences, undergraduate level.
    Livet efter att ha drabbats av en hjärtinfarkt2015Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Cardiac care has developed during the last years. The lengths of stay for patients who have suffered a myocardial infarction have been shortened thanks to more effective medical treatment. The short period of care means that patients have to absorb a lot of information on limited time and they may have difficulties absorbing everything before they leave the hospital.

    The aim of this study is to highlight how men and women experience and manage their daily lives three to 12 month after a myocardial infarction. The study is literature based including both qualitative and quantitative studies.

    The analysis revealed three themes with subthemes: 1) to no longer be able to rely on the body 2) managing daily life 3) support. It turns out that men and women have numerous emotional experiences and that fatigue plays a big role in their recovery. Men and women deal with their situation differently. Family and friends mean a lot in the rehabilitation and nurses play an important role in supporting those affected and this is an area with a lot of work to develop.

    Conclusion: Nurses need knowledge and understanding of how patients manage and experience their situation after a myocardial infarction, as well as learning the importance of meeting each individual differently, depending on where he or she is in life and what his or her nearest environment look like. A more individualized follow-up and rehabilitation over time need to be developed.

  • 6.
    Aagaard, Lise
    et al.
    University of So Denmark, Denmark FKL Research Centre Qual Medical Use, Denmark Danish Pharmacovigilance Research Project DANPREP, Denmark .
    Strandell, Johanna
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Melskens, Lars
    University of Copenhagen, Denmark .
    Petersen, Paw S. G.
    University of Copenhagen, Denmark .
    Holme Hansen, Ebba
    FKL Research Centre Qual Medical Use, Denmark Danish Pharmacovigilance Research Project DANPREP, Denmark University of Copenhagen, Denmark .
    Global Patterns of Adverse Drug Reactions Over a Decade Analyses of Spontaneous Reports to VigiBase (TM)2012In: Drug Safety, ISSN 0114-5916, E-ISSN 1179-1942, Vol. 35, no 12, 1171-1182 p.Article in journal (Refereed)
    Abstract [en]

    Background: Although systems to collect information about suspected adverse drug reactions (ADRs) were established in many countries and by the WHO in the 1960s, few studies have examined reported ADRs related to national income. Objective: The aim of the study was to characterize ADRs reported to the WHO-ADR database, VigiBase (TM), and to relate data to national income. Methods: We analysed ADR reports submitted to VigiBase (TM) from 2000 to 2009 with respect to reporting rate, age and sex of patient, type, seriousness and medications. Reports were also analysed with respect to national income level, classified in accordance with the World Bank definition: low, lower-middle, upper-middle and high. Results: We analysed 1 359 067 ADR reports including 3 013 074 ADRs. Overall, 16% of reports were serious and 60% were reported for females. High-income countries had the highest ADR reporting rates (range 3-613 reports/million inhabitants/year) and low-income countries the lowest (range 0-21). Distribution of ADRs across income groups with respect to age group, seriousness and sex was non-significant. Overall, the majority of ADRs were reported for nervous system medications, followed by cardiovascular medicines. Low-income countries reported relatively more ADRs for antiinfectives for systemic use than high-income countries, and high-income countries reported more ADRs for antineoplastic and immunomodulating agents than lower-income groups. Conclusion: This study showed that high-income countries had the highest ADR reporting rates and low-income countries the lowest, with large variations across countries in each group. Significant differences in ADR reporting rates were only found for ADRs of the type skin and subcutaneous tissue disorders and for the therapeutic groups antiinfectives for systemic use and antineoplastic and immunomodulation agents. To strengthen ADR reporting rates, especially in low-income countries, more research is needed about the impact of organizational structures and economic resources of national pharmacovigilance centres and ADR reporting practices on the large variations in ADR reporting rates within income groups.

  • 7.
    Aagesson, Ingela
    et al.
    Blekinge Institute of Technology, School of Health Science.
    Hammarström, Matilda
    Blekinge Institute of Technology, School of Health Science.
    Vad är det för vits med humor i vården?2006Independent thesis Basic level (degree of Bachelor)Student thesis
    Abstract [sv]

    Bakgrund. Skratt och humor inom vården kan minska stress, oro, rädsla och utbrändhet. Humor kan även bygga relationer och lätta upp stämningen. Humor kan användas som kommunikationsmedel mellan människor. Syfte. Syftet med studien var att belysa hur humor i vården påverkar patienter och personal. Metod. Litteraturstudie där sju vetenskapliga artiklar granskades och analyserades med inspiration av Graneheim och Lundmans (2004) analysmodell. Resultat. Studiens resultat påvisade att humor ansågs ha en viktig funktion i vården. Humor hjälpte till att bemästra svåra situationer, att hantera känslor, bidra till välbefinnande och påverka relationen och kommunikationen. Slutsats. Inom vården uppfattades humor vara viktig för både vårdpersonal och patienter. Humor ansågs kunna påverka patienter och vårdpersonal genom att vara en hjälp till att bemästra situationer, bidra till välbefinnande, hantera känslor och underlätta relationen och kommunikationen.

  • 8.
    Aahlin, Eirik K
    et al.
    Department of GI and HPB Surgery, University Hospital Northern Norway, Breivika, Tromsø, Norway; Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway .
    von Meyenfeldt, Maarten
    Department of Surgery, University Hospital Maastricht and NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht, The Netherlands .
    Dejong, Cornelius Hc
    Department of Surgery, University Hospital Maastricht and NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht, The Netherlands .
    Ljungqvist, Olle
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Surgery, Örebro University Hospital, Örebro; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm.
    Fearon, Kenneth C
    Clinical Surgery, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK .
    Lobo, Dileep N
    Division of Gastrointestinal Surgery, Nottingham Digestive Diseases Centre National Institute for Health Research, Biomedical Research Unit, Nottingham University Hospitals, Queen's Medical Centre, Nottingham, UK .
    Demartines, Nicolas
    Hospital of Lausanne (CHUV), Lausanne, Switzerland .
    Revhaug, Arthur
    Department of GI and HPB Surgery, University Hospital Northern Norway, Breivika, Tromsø, Norway; Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway .
    Wigmore, Stephen J
    Clinical Surgery, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK .
    Lassen, Kristoffer
    Department of GI and HPB Surgery, University Hospital Northern Norway, Breivika, Tromsø, Norway; Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway .
    Functional recovery is considered the most important target: a survey of dedicated professionals2014In: Perioperative medicine, ISSN 2047-0525, Vol. 3, 3:5Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to survey the relative importance of postoperative recovery targets and perioperative care items, as perceived by a large group of international dedicated professionals.

    Methods: A questionnaire with eight postoperative recovery targets and 13 perioperative care items was mailed to participants of the first international Enhanced Recovery After Surgery (ERAS) congress and to authors of papers with a clear relevance to ERAS in abdominal surgery. The responders were divided into categories according to profession and region.

    Results: The recovery targets 'To be completely free of nausea', 'To be independently mobile' and 'To be able to eat and drink as soon as possible' received the highest score irrespective of the responder's profession or region of origin. Equally, the care items 'Optimizing fluid balance', 'Preoperative counselling' and 'Promoting early and scheduled mobilisation' received the highest score across all groups.

    Conclusions: Functional recovery, as in tolerance of food without nausea and regained mobility, was considered the most important target of recovery. There was a consistent uniformity in the way international dedicated professionals scored the relative importance of recovery targets and care items. The relative rating of the perioperative care items was not dependent on the strength of evidence supporting the items.

  • 9. Aahlin, Kristofer
    et al.
    Arvidsson, Per I.
    Huerta, Fernando
    Yngve, Ulrika.
    Preparation of 1-(4-(5-amino-6-(oxazolo[4,5-c]pyridin-2-yl)pyrazin-2-yl)benzoyl)piperazine derivatives as glycogen synthase kinase 3 inhibitors.2011Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    Title compds. I [R1 = H or Me], and their pharmaceutically acceptable salts, are prepd. and disclosed as glycogen synthase kinase 3 (GSK3) inhibitors. Thus, e.g., II was prepd. by cyclization of 3-amino-N-(4-hydroxypyridin-3-yl)pyrazine-2-carboxamide (prepn. given) to get intermediate 3-(oxazolo[4,5-c]pyridin-2-yl)pyrazin-2-amine, which underwent bromination followed by Suzuki reaction with (4-methylpiperazin-1-yl)(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanone. Compds. of the invention were tested for their selective inhibitory activity of GSK3β, e.g., II exhibited Ki value of 2.3 nM. The invention compds. are useful for the treatment of cognitive disorders, diabetes, cancer, etc. [on SciFinder(R)]

  • 10. Aalborg, T.
    et al.
    Strandmark, Margaretha
    Karlstad University, Faculty of Social and Life Sciences, Department of Health and Environmental Sciences.
    The baby was the focus of attention: First-time patients' experiences of their marital relationship2001In: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 15, 318-325 p.Article in journal (Refereed)
  • 11. Aalborg, T.
    et al.
    Strandmark, Margaretha
    Karlstad University, Faculty of Social and Life Sciences, Department of Health and Environmental Sciences.
    Dahlöf, LG
    First time parents' sexual relationschips2000In: Scandinavian Journal of Sexology 3; 127-139Article in journal (Refereed)
  • 12.
    Aalto, Anne
    et al.
    Linköping University, Department of Medicine and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medicine and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Jaworski, M
    Gustavsson, M
    Tisell, Anders
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medicine and Health Sciences, Radiation Physics. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL. Linköping University, Faculty of Health Sciences.
    Landtblom, Anne-Marie
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Clinical and Experimental Medicine, Psychiatry. Östergötlands Läns Landsting, Sinnescentrum, Department of Neurosurgery UHL. Linköping University, Faculty of Health Sciences.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medicine and Health Sciences, Radiation Physics. Linköping University, Department of Medicine and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics UHL. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Radiology in Linköping. Linköping University, Faculty of Health Sciences.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medicine and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Radiology in Linköping. Linköping University, Faculty of Health Sciences.
    Effects of Betainterferon treatment in Multiple Sclerosis Studied by Quantitative 1H MRS2009Conference paper (Other academic)
  • 13.
    Aalto, Anne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Sjoewall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Davidsson, Leif
    Linköping University, Department of Medicine and Care, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Smedby, Örjan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Brain magnetic resonance imaging does not contribute to the diagnosis of chronic neuroborreliosis2007In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 48, no 7, 755-762 p.Article in journal (Refereed)
    Abstract [en]

    Background: Borrelia infections, especially chronic neuroborreliosis ( NB), may cause considerable diagnostic problems. This diagnosis is based on symptoms and findings in the cerebrospinal fluid but is not always conclusive. Purpose: To evaluate brain magnetic resonance imaging ( MRI) in chronic NB, to compare the findings with healthy controls, and to correlate MRI findings with disease duration. Material and Methods: Sixteen well- characterized patients with chronic NB and 16 matched controls were examined in a 1.5T scanner with a standard head coil. T1- ( with and without gadolinium), T2-, and diffusion- weighted imaging plus fluid- attenuated inversion recovery ( FLAIR) imaging were used. Results: White matter lesions and lesions in the basal ganglia were seen in 12 patients and 10 controls ( no significant difference). Subependymal lesions were detected in patients down to the age of 25 and in the controls down to the age of 43. The number of lesions was correlated to age both in patients ( rho=0.83, P < 0.01) and in controls ( rho=0.61, P < 0.05), but not to the duration of disease. Most lesions were detected with FLAIR, but many also with T2- weighted imaging. Conclusion: A number of MRI findings were detected in patients with chronic NB, although the findings were unspecific when compared with matched controls and did not correlate with disease duration. However, subependymal lesions may constitute a potential finding in chronic NB.

  • 14.
    Aalto, Maarit
    et al.
    Nordic Council of Ministers, Nordic Centre for Welfare and Social Issues.
    Stankovic, Nenad
    Sällsynt samverkan för nordisk välfärd: Kartläggning av möjliga nordiska samarbetsområden anknutna till små och sällsynta diagnosgrupper2010Other (Other (popular science, discussion, etc.))
  • 15.
    Aalto, Mervi Anneli
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Vill kunder handla receptfria läkemedel i dagligvaruhandeln?: - En enkätundersökning2008Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpStudent thesis
    Abstract [sv]

    Sammanfattning

    I Sverige har det statliga apoteketsmonopolet ifrågasatts en längre tid och regeringen utreder nu möjligheten att konkurrensutsätta läkemedelsförsäljningen. Det har även föreslagits i den statliga utredningen (SOU 2008:4 del 2) att ett begränsat sortiment av OTC läkemedel (over the counter = receptfria läkemedel) ska få säljas i dagligvaruhandeln utan farmaceutiskt kompetenskrav. Vid korrekt användning och tillgång till rätt rådgivning kan OTC läkemedel vara till en stor hjälp för den enskilde individen vid egenvård och därigenom också bidra till avlastning på sjukvårdens resursers. Vid felanvändning av OTC läkemedel (över/underdosering, fel indikationsområde etc.), kan de istället få motsatt effekt. Syftet med denna enkätstudie var därför att utforska om konsumenter av OTC läkemedel i Sverige önskar få tillgång till dessa läkemedel i t ex livsmedelsbutiker, där de inte har tillgång till personlig farmaceutisk rådgivning, vidare var avsikten att undersöka hur de i dagligvaruhandeln önskade få läkemedelsinformation. I februari 2008 gjordes en enkätstudie i Västervik som inkluderade 48 deltagare varav 29 kvinnor och 19 män. Studien visade att 71 % av deltagarna hade en positiv inställning till att köpa OTC läkemedel i livsmedelsbutiker, 58 % skulle skaffa information genom läkemedelsförpackning och bipacksedel i kombination med att de tidigare använt läkemedlet. Önskan om tillgång till personlig rådgivning på inköpsstället var störst i åldern ≤ 35 år, där 38 % ansåg sig vilja det. Slutsats av studien är att majoriteten vill kunna handla OTC läkemedel i dagligvaruhandeln och information skulle de få främst från läkemedelsförpackning/bipacksedel i kombination med erfarenheter från tidigare användning.

    2008:F5

  • 16. Aaltonen, Kirsimari
    et al.
    Ahlin, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Salonen, Laura
    Fjällskog, Marie Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Heikkilä, Pävi
    Nevanlinna, Heli
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Reliability of cyclin A assessment on tissue microarrays in breast cancer compared to conventional histological slides2006In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 94, no 11, 1697-1702 p.Article in journal (Refereed)
    Abstract [en]

    Cyclin A has in some studies been associated with poor breast cancer survival, although all studies have not confirmed this. Its prognostic significance in breast cancer needs evaluation in larger studies. Tissue microarray (TMA) technique allows a simultaneous analysis of large amount of tumours on a single microscopic slide. This makes a rapid screening of molecular markers in large amount of tumours possible. Because only a small tissue sample of each tumour is punched on an array, the question has arisen about the representativeness of TMA when studying markers that are expressed in only a small proportion of cells. For this reason, we wanted to compare cyclin A expression on TMA and on traditional large sections. Two breast cancer TMAs were constructed of 200 breast tumours diagnosed between 1997-1998. TMA slides and traditional large section slides of these 200 tumours were stained with cyclin A antibody and analysed by two independent readers. The reproducibility of the two readers' results was good or even very good, with kappa values 0.71-0.87. The agreement of TMA and large section results was good with kappa value 0.62-0.75. Cyclin A overexpression was significantly (P<0.001) associated with oestrogen receptor and progesterone receptor negativity and high grade both on TMA and large sections. Cyclin A overexpression was significantly associated with poor metastasis-free survival both on TMA and large sections. The relative risks for metastasis were similar on TMA and large sections. This study suggests that TMA technique could be useful to study histological correlations and prognostic significance of cyclin A on breast cancer on a large scale.

  • 17. Aaltonen, Kirsimari
    et al.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Heikkilä, Päivi
    Aittomäki, Kristiina
    Tamminen, A.
    Nevanlinna, Heli
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    High cyclin B1 expression is associated with poor survival in breast cancer2009In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 100, no 7, 1055-60 p.Article in journal (Refereed)
    Abstract [en]

    Cyclin B1 regulates the G(2)-M transition of the cell cycle. Cyclin B1 expression is higher in premalignant and malignant than normal breast lesions. Correlation of cyclin B1 expression with other histopathological variables and prognostic role in breast cancer are not fully understood. Traditionally used prognostic criteria identify large subset of patients to receive adjuvant chemotherapy and to be exposed to adverse effects. A reliable and simple method helping prognostic evaluation in breast cancer is needed. We analysed cyclin B1 expression on 1348 invasive breast cancers and studied correlations with other histopathological variables and survival. High cyclin B1 correlated with high tumour grade, large tumour size and positive nodal status, oestrogen and progesterone receptor negativity, positive HER2 and p53 status, young age at diagnosis, and high cyclin E, cyclin A and Ki67 expression. Among patients not given adjuvant chemotherapy high cyclin B1 was a strong predictor of shorter overall and metastasis-free survival (RR 3.74, P<0.0005 and RR 3.51, P<0.0005, respectively), and remained as an independent prognostic factor also in multivariate analysis (RR 1.80, P=0.04 and RR 2.31, P=0.02, respectively). This study suggests high cyclin B1 associates with aggressive phenotype and is an independent prognostic factor in breast cancer.

  • 18. Aaltonen, Kirsimari
    et al.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Landberg, Göran
    Eerola, Hannaleena
    Aittomäki, Kristiina
    Heikkilä, Päivi
    Nevanlinna, Heli
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Cyclin D1 expression is associated with poor prognostic features in estrogen receptor positive breast cancer2009In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 113, no 1, 75-82 p.Article in journal (Refereed)
    Abstract [en]

    Cyclins D1 and E play an important role in breast carcinogenesis. High cyclin E expression is common in hormone receptor negative and high grade aggressive breast cancer, whereas cyclin D1 in hormone receptor positive and low grade breast cancer. Experimental data has suggested that cyclin D1 and E mediate cell proliferation by different mechanisms in estrogen receptor (ER) positive and negative breast cancer. To test this hypotheses in large breast cancer material and to clarify the histopathological correlations of cyclin E and D1, especially the association with proliferation, we analyzed cyclin E and D1 immunohistochemical expression on breast tumour microarrays consisting of 1348 invasive breast cancers. High cyclin D1 expression was associated with high grade (P<0.0005), high cyclin A (P<0.0005) and Ki67 (P<0.0005) expression among ER positive but with low grade (P=0.05) and low Ki67 (P=0.01) expression among ER negative breast cancers. Cyclin E and D1 expression correlated positively in ER positive (P<0.0005) but had a negative correlation in ER negative tumours (P=0.004). Cyclin E associated with high grade among all tumours (P<0.0005). In conclusion, the findings of this study show that cyclin D1 has separate roles, and proliferation is driven by different mechanisms in ER positive and negative breast cancers.

  • 19. Aaltonen, Kirsimari
    et al.
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Eerola, Hannaleena
    Aittomäki, Kristiina
    Heikkilä, Päivi
    Nevanlinna, Heli
    Familial breast cancers without mutations in BRCA1 or BRCA2 have low cyclin E and high cyclin D1 in contrast to cancers in BRCA mutation carriers2008In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 14, no 7, 1976-83 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We analyzed the expression of critical cell cycle regulators cyclin E and cyclin D1 in familial breast cancer, focusing on BRCA mutation-negative tumors. Cyclin E expression in tumors of BRCA1 or BRCA2 carriers is higher, and cyclin D1 expression lower, than in sporadic tumors. In familial non-BRCA1/2 tumors, cyclin E and cyclin D1 expression has not been studied. EXPERIMENTAL DESIGN: Cyclin E and cyclin D1 immunohistochemical expression was studied in tissue microarrays consisting of 53 BRCA1, 58 BRCA2, 798 familial non-BRCA1/2, and 439 sporadic breast tumors. RESULTS: In univariate analysis, BRCA1 tumors had significantly more frequently high cyclin E (88%) and low cyclin D1 (84%) expression than sporadic (54% and 49%, respectively) or familial non-BRCA1/2 (38% and 45%, respectively) tumors. BRCA2 tumors had significantly more frequently low cyclin D1 expression (68%) than sporadic or familial non-BRCA1/2 tumors and significantly more frequently high cyclin E expression than familial non-BRCA1/2 tumors. In a logistic regression model, cyclin expression, early age of onset, and estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER2) status were the independent factors most clearly distinguishing tumors of BRCA1 mutation carriers from other familial breast cancers. High cyclin E and low cyclin D1 expression were also independent predictors of BRCA2 mutation when compared with familial non-BRCA1/2 tumors. Most interestingly, lower frequency of high cyclin E expression independently distinguished familial non-BRCA1/2 tumors also from sporadic ones. CONCLUSIONS: Cyclin E and cyclin D1 expression distinguishes non-BRCA1/2 tumors from both sporadic and BRCA1- and BRCA2-associated tumors and may reflect different predisposition and pathogenesis in these groups.

  • 20.
    Aaltonen, Kristina E.
    et al.
    Lund University, Sweden.
    Rosendahl, Ann H.
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Malmstrom, Per
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Hartman, Linda
    Lund University, Sweden; Regional Cancer Centre South, Sweden.
    Ferno, Marten
    Lund University, Sweden.
    Association between insulin-like growth factor-1 receptor (IGF1R) negativity and poor prognosis in a cohort of women with primary breast cancer2014In: BMC Cancer, ISSN 1471-2407, Vol. 14, no 794Article in journal (Refereed)
    Abstract [en]

    Background: Resistance towards endocrine therapy is a great concern in breast cancer treatment and may partly be explained by the activation of compensatory signaling pathways. The aim of the present study was to investigate if the insulin-like growth factor-1 receptor (IGF1R) signaling pathway was activated or deregulated in breast cancer patients and to explore if any of the markers were prognostic, with or without adjuvant tamoxifen. This signaling pathway has been suggested to cause estrogen independent cell growth and thus contribute to resistance to endocrine treatment in estrogen receptor (ER) positive breast cancer. Methods: The protein expression of IGF1R, phosphorylated Mammalian Target of Rapamycin (p-mTOR) and phosphorylated S6 ribosomal protein (p-S6rp) were investigated by immunohistochemistry using tissue microarrays in two patient cohorts. Cohort I (N = 264) consisted of mainly postmenopausal women with stage II breast cancer treated with tamoxifen for 2 years irrespective of ER status. Cohort II (N = 206) consisted of mainly medically untreated, premenopausal patients with node-negative breast cancer. Distant disease-free survival (DDFS) at 5 years was used as end-point for survival analyses. Results: We found that lower IGF1R expression was associated with worse prognosis for tamoxifen treated, postmenopausal women (HR = 0.70, 95% CI = 0.52 - 0.94, p = 0.016). The effect was seen mainly in ER-negative patients where the prognostic effect was retained after adjustment for other prognostic markers (adjusted HR = 0.49, 95% CI = 0.29 - 0.82, p = 0.007). Expression of IGF1R was associated with ER positivity (p less than 0.001) in the same patient cohort. Conclusions: Our results support previous studies indicating that IGF1R positivity reflects a well differentiated tumor with low metastatic capacity. An association between lack of IGF1R expression and worse prognosis was mainly seen in the ER-negative part of Cohort I. The lack of co-activation of downstream markers (p-mTOR and p-S6rp) in the IGF1R pathway suggested that the prognostic effect was not due to complete activation of this pathway. Thus, no evidence could be found for a compensatory function of IGF1R signaling in the investigated cohorts.

  • 21. Aaltonen, Minna
    et al.
    Soukka, Hanna
    Halkola, Lauri
    Jalonen, Jarmo
    Kalimo, Hannu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Holopainen, Irma E
    Kääpä, Pekka O
    Inhaled nitric oxide treatment inhibits neuronal injury after meconium aspiration in piglets2007In: Early Human Development, ISSN 0378-3782, Vol. 83, no 2, 77-85 p.Article in journal (Refereed)
    Abstract [en]

    Background: Meconium aspiration-induced hypertensive lung injury is frequently associated with neuronal damage. Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension, but its effects on the brain are poorly known. Aims: The aim of this study was to determine the effects of iNO treatment on the neuronal tissue after meconium aspiration. Study design: 71 anesthetized, catheterized and ventilated newborn piglets were studied for 6 h. Thirty-five piglets were instilled with a bolus of human meconium intratracheally and 36 piglets with saline instillation served as controls. Nineteen meconium piglets and 17 control piglets were continuously treated with 20 ppm of iNO, started at 30 min after the insult. The extent of neuronal injury was analysed histologically, and the levels of brain tissue lipid peroxidation products, reduced glutathione (GSH), myeloperoxidase activity and oxidized DNA were analysed as indicators of oxidative stress. Results: iNO treatment diminished the pulmonary hypertensive response caused by meconium aspiration, but did not change systemic or carotid hemodynamics. NO administration was associated with reduced neuronal injury and diminished amount of oxidized DNA in the hippocampus of the meconium piglets. Further, iNO treatment was associated with decreased level of GSH in the cortex, but no change in lipid peroxidation production or myeloperoxidase activity was detected in any of the studied brain areas. Conclusions: Our results suggest that iNO treatment may inhibit DNA oxidation and neuronal injury in the hippocampus, associated with newborn meconium aspiration.

  • 22. Aalto-Setälä, Katriina
    et al.
    Palomäki, Heikki
    Miettinen, Helena
    Vuorio, Alpo
    Kuusi, Timo
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Salonen, Oili
    Kaste, Markku
    Kontula, Kimmo
    Genetic risk factors and ischemic cerebrovascular disease: role of common variation of the genes encoding apolipoproteins and angiotensin-converting enzyme1998In: Annals of Medicine, ISSN 0785-3890, Vol. 30, no 2, 224-33 p.Article in journal (Refereed)
    Abstract [en]

    DNA polymorphisms in genes encoding apolipoproteins (apo) A-I, C-III, B and E and angiotensin-converting enzyme (ACE) have been proposed to be associated with the risk of coronary artery disease (CAD). We studied whether the same genetic markers would also be associated with the occurrence and extent of atherosclerosis in cervical arteries. DNA samples from 234 survivors of stroke or a transient ischaemic attack aged 60 years or less were examined. The presence of atherosclerosis was assessed using aortic arch angiograms. The SstI polymorphism of apoA-I/C-III gene locus, the XbaI polymorphism of apoB gene, common apoE phenotypes and the insertion/deletion polymorphism of the ACE gene were analysed. The allele frequencies of the apoA-I/C-III, apoB, apoE or ACE gene did not differ between the groups with (n = 148) or without (n = 85) cervical atherosclerosis. However, when patients with at least one apoE4 allele and one X2 allele of apoB were combined and compared with those without either of them (E2E3 or E3E3 and X1X1), a significant association with the presence of cervical atherosclerosis was found (P = 0.03). The patients having the E2E3 phenotype had a significantly elevated serum triglyceride level compared with those with the E3E3 phenotype (P = 0.03). Serum high-density lipoprotein (HDL) cholesterol was lower in the patients with the E2E3 phenotype than in those with the E3E3 and E3E4 (P = 0.01 and P = 0.06, respectively). The apoB or ACE genotypes were not significantly associated with serum lipid or lipoprotein levels. There was no association between the ACE gene polymorphism and the occurrence of hypertension. In conclusion, the interaction of common apoB and apoE alleles may increase the risk of atherosclerosis in cervical arteries.

  • 23.
    Aamand Grabau, Dorthe
    et al.
    Skåne University Hospital, Sweden .
    Bendahl, Par-Ola
    Lund University, Sweden .
    Ryden, Lisa
    Lund University, Sweden .
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Ferno, Marten
    Lund University, Sweden .
    The prevalence of immunohistochemically determined oestrogen receptor positivity in primary breast cancer is dependent on the choice of antibody and method of heat-induced epitope retrieval - prognostic implications?2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 8, 1657-1666 p.Article in journal (Refereed)
    Abstract [en]

    Background. Oestrogen receptor (ER) status is important for the choice of systemic treatment of breast cancer patients. However, most data from randomised trials on the effect of adjuvant endocrine therapy according to ER status are based on the cytosol methods. Comparisons with immunohistochemical methods have given similar results. The aim of the present study was to examine whether different ER antibodies and heat-induced epitope retrieval (HIER) methods influence the prevalence of ER-positivity in primary breast cancer. Material and methods. This study is based on patients included in a clinical trial designed to compare the effect of two years of adjuvant tamoxifen versus no adjuvant systemic treatment in premenopausal women. From 1986 to 1991, 564 patients from two study centres in Sweden were enrolled and randomised. Patients were randomised independently of ER status. In the present study, ER status was assessed on tissue microarrays with the three different ER antibody/HIER combinations: 1D5 in citrate pH 6 (n = 390), SP1 in Tris pH 9 (n = 390) and PharmDx in citrate pH 6 (n = 361). Results. At cut-offs of 1% and 10%, respectively, the prevalence of ER-positivity was higher with SP1 (75% and 72%) compared with 1D5 (68% and 66%) and PharmDx (66% and 62%). At these cut-offs, patients in the discordant groups (SP1-positive and 1D5-negative) seem to have a prognosis intermediate between those of the double-positive and double-negative groups. Comparison with the ER status determined by the cytosol-based methods in the discordant group also showed an intermediate pattern. The repeatability was good for all antibodies and cut-offs, with overall agreement andgt;= 93%. Conclusion. The present study shows that the choice of antibody and HIER method influences the prevalence of ER-positivity. We suggest that this be taken into consideration when choosing a cut-off for clinical decision making.

  • 24.
    Aanaes, K
    et al.
    Rigshosp, Denmark .
    Rasmussen, N
    Rigshosp, Denmark Statens Serum Institute, Denmark .
    Pressler, T
    Rigshosp, Denmark Rigshosp, Denmark .
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Nephrology UHL.
    Johansen, H K
    Rigshosp, Denmark .
    Lindberg, U
    Lund University, Sweden .
    Hoiby, N
    Rigshosp, Denmark .
    Carlsson, M
    Lund University, Sweden .
    Wieslander, J
    EuroDiagnostica AB, Sweden .
    Buchwald, C
    Rigshosp, Denmark .
    Extensive Endoscopic Image-Guided Sinus Surgery Decreases BPI-ANCA in Patients with Cystic Fibrosis2012In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 76, no 6, 573-579 p.Article in journal (Refereed)
    Abstract [en]

    Antineutrophil cytoplasm autoantibodies (ANCA) directed against bactericidal/permeability-increasing protein (BPI) are common in patients with cystic fibrosis (CF), and serum levels are correlated with lung colonization by Pseudomonas aeruginosa and the severity of lung damage. The production of BPI-ANCA may be due to the costimulation of BPI when mounting an immune response against P. aeruginosa. The effect of surgery aiming to eradicate bacteria and infected tissue on BPI-ANCA levels is sparsely described. A cohort of patients with CF were included: 53 patients having extensive image-guided sinus surgery (EIGSS) with topical postoperative antibiotic treatment, 131 non-operated controls and 36 who had double lung transplantation (LTX). In all 219 patients, serum samples before and after surgery or at similar intervals were analysed for IgG and IgA BPI-ANCA. The EIGSS group showed a highly significant decrease in both IgA and IgG BPI-ANCA levels compared with their own preoperative values and control group values (P andlt; 0.0010.02). The LTX patients also showed a highly significant decrease in both IgA and IgG BPI-ANCA levels (P andlt; 0.001). EIGSS and LTX decrease IgA and IgG BPI-ANCA levels in patients with CF, indicating that extensive removal of infected tissue influences the pathogenic process of autoantibody production. The results shown herein are in favour of applying EIGSS in selected patients with CF and for using BPI-ANCA as a surrogate marker for guiding further therapeutic interventions.

  • 25. Aanesen, Arthur
    et al.
    Westerbotn, Margareta
    Sophiahemmet University.
    Prospective study of a Swedish infertile cohort 2005-08: population characteristics, treatments and pregnancy rates2014In: Family Practice, ISSN 0263-2136, E-ISSN 1460-2229, Vol. 31, no 3, 290-7 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We here report on results from a prospective study comprising 380 infertile couples undergoing infertility work-up and various treatments for infertility in our clinic. The aim was to investigate the overall birth rate as a result of different treatments, as well as spontaneous pregnancies.

    METHODS: Three hundred and eighty couples were consecutively included between December 2005 and May 2008. All couples underwent a fertility work-up, including hysterosalpingogram, hormonal characterization, clinical examination, screening for infectious diseases and semen analysis. The mean age of the women at the time of inclusion was 33.2 years. The mean duration of infertility prior to inclusion was 1.8 years. And 46.6% (n = 177) of the women had been pregnant prior to their first visit to the clinic and 30.0% (n = 114) had been pregnant earlier in their present relationship.

    RESULTS: As of November 2010, 57.3% (n = 218) of the women had given birth to a child when they were lost to follow up by the study. Spontaneous conception was observed in 11.3% (n = 43) of the women, 14.5% (n = 64) conceived after intrauterine insemination (IUI), 4.2% (n = 16) conceived after ovarian hyperstimulation and ovulation induction (OH/OI) and 28.4% (n = 113) after in vitro fertilization. There were 280 pregnancies and 58 spontaneous abortions (22.3%) in the group. Mean anti-mullerian hormone significantly correlated with antral follicle count and age and was significantly higher in the subgroup that became pregnant after IUI.

    CONCLUSIONS: Spontaneous pregnancies and IUI + OH/OI contributed significantly to the pregnancies observed in the total population. Predictive factors for pregnancy were anti-mullerian hormone in the group undergoing IUI treatment and in the age group ≥38-duration of infertility. Previous pregnancies, body mass index, estradiol, follicle stimulating hormone or having given birth prior to the infertility period were not predictive of pregnancy for the infertile couples in this study.

  • 26.
    Aanestad, Øystein
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Quantitative electromyographic studies of the perineal muscles in normal subjects and patients suffering from anal or urinary incontinence1998Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aims of the study were to characterize the interference pattern in perineal muscles in healthy subjects with the use of quantitative EMG techniques, to evaluate if prostatic surgery had any effect on the interference pattern and furthermore to examine the interference pattern in the perineal muscles in patients suffering from urinary or anal incontinence.

    The interference pattern in the perineal muscles was examined with a computerized analysis, the Turns and Amplitude (T/A) analysis, and the innervation pattern of the muscles was examined with single fiber electromyography measuring the fiber density. Reference values were collected from 30 normal subjects. The patient material consisted of 20 males subjected to transurethral prostatectomy (TUR-P), 10 males who underwent radical retropubic prostatectomy (RRP), 20 patients suffering from anal incontinence and 24 women withurinary incontinence.

    T/A analysis of the interference pattern in the perineal muscles in normal subjects showed a significant increase in number of turns/sec and mean amplitude correlating to increasing force but no age-related changes.

    TUR-P and RRP did effect the innervation of the distal urethral sphincter muscle as shown by increased fiber density indicating a peripheral nerve lesion. T/A analysis did not shown any increased activation of the distal urethral sphincter as a compensation for the loss in bladder neck sphincter function but rather signs of decreasedcentral activation.

    Patients with idiopathic faecal incontinence showed signs of impaired innervation of the external anal sphincter muscle. A decreased interference pattern at maximal contraction indicated a reduced central activation of perineal muscles, in particular for patients with partial rupture of the external anal sphincter muscle. The reduced central activation could play a role for the aetiology of faecal incontinence.

    Patients with urinary stress incontinence also showed signs of impaired innervation of the external anal sphincter muscle as well as reduced interference pattern at maximal contraction and during continuous recording of the EMG activity during cystometry. A reduced central activation of the motor units was predicted as one factor involved in the aetiology.

  • 27. Aapro, Matti
    et al.
    Beguin, Yves
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gascon, Pere
    Hedenus, Michael
    Österborg, Anders
    Too-Low Iron Doses and Too Many Dropouts in Negative Iron Trial?2011In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 29, no 17, E525-E526 p.Article in journal (Refereed)
  • 28. Aapro, Matti S.
    et al.
    Birgegård, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bokemeyer, Carsten
    Cornes, Paul
    Foubert, Jan
    Gascon, Pere
    Glaspy, John
    Hellström-Lindberg, Eva
    Link, Hartmut
    Ludwig, Heinz
    Österborg, Anders
    Repetto, Lazzaro
    Soubeyran, Pierre
    Erythropoietins should be used according to guidelines2008In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 9, no 5, 412-3 p.Article in journal (Refereed)
  • 29.
    Aarao, J
    et al.
    University of S Australia, Australia .
    Miklavcic, Stan J.
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    Ward, D A.
    University of S Australia, Australia .
    Extended-domain-eigenfunction method (EDEM): a study of ill posedness and regularization2013In: Journal of Physics A: Mathematical and Theoretical, ISSN 1751-8113, Vol. 46, no 8Article in journal (Refereed)
    Abstract [en]

    The extended-domain-eigenfunction method (EDEM) proposed for solving elliptic boundary value problems on annular-like domains requires an inversion process. The procedure thus represents an ill-posed problem, whose numerical solution involves an ill-conditioned system of equations. In this paper, the ill-posed nature of EDEM is studied and numerical solutions based on regularization schemes are considered. It is shown that the EDEM solution methodology lends itself naturally to a formulation in terms of the well-known iterative Landweber method and the more general and faster converging semi-iterative regularization schemes. Theoretical details and numerical results of the regularization schemes are presented for the case of the two-dimensional Laplace operator on annular domains.

  • 30.
    Aardal, Elisabeth
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Ann-Charlotté, Holm
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Cortisol in Saliva: Reference Ranges and Relation to Cortisol in Serum1995In: European Journal of Clinical Chemistry and Clinical Biochemistry, ISSN 0939-4974, Vol. 33, 927-932 p.Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to establish morning and evening reference ranges for cortisol in saliva. Another objective was to compare the concentrations of the mainly free cortisol in saliva to those of total cortisol in serum as determined with a commercial radioimmunoassay. The concentrations were determined in matched samples of saliva and serum collected at 8am and 10pm from 197 healthy volunteers. The saliva samples were stable for at least 7 days at room temperature and for 9 months at —20 °C. Reference ranges, the central 95%, were estimated to 3.5—27.0 nmol/1 at 8 am and < 6.0 nmol/1 at 10 pm. The intra-assay coefficient of variation (CV) was below 5% and total CV below 10%. The relation between the cortisol concentrations in serum and saliva was nonlinear with r = 0.86 for serum concentrations < 450 nmol/1 and r = 0.44 for serum concentrations ^ 450 nmol/1. In conclusion, the satisfactory precision of the analysis and the simple non-invasive sampling procedure suggest that saliva may be used for cortisol measurements in situations where blood sampling is difficult to perform.

  • 31.
    Aardal-Eriksson, Elisabeth
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Salivary cortisol and posttraumatic stress reactions: methodological and applied studies before and after trauma2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The field of psychotraumatology has its roots in ancient history. During the past decades, the surveillance of the psychobiological background of reactions to and consequences of traumatic stress has made great progress and the complexity of the human stress response system stands out. The hypothalamic-pituitary-adrenocortical axis activity, modulated by various neuroimmunological substances, seems to play a major role in the stress response. However, there are still inconsistencies in explanations of relationships between biological and psychological changes following traumatic stress. Moreover, the matter of predictive factors for the development of posttraumatic morbidity is still in a speculative phase.

    The aims of the present thesis were to further develop a commercial serum cortisol radioimmunoassay (RIA) for determination of cortisol in saliva and to test its reliability, specificity and sensitivity as a biochemical assay. The saliva sampling procedures and sample storage stability were also to be tested. Further issues were to investigate determinations of salivary cortisol and serum prolactin in relation to selfratings of posttraumatic psychological distress and general psychological health. Possible predictive and concurrent validity of salivary cortisol as a biochemical marker for posttraumatic psychological distress were to be tested.

    Cortisol is present in saliva mainly in non-protein form, representing the free, biologically active fraction of the total plasma cortisol concentration. In a first phase of the present thesis, the commercial serum cortisol RIA was modified for determination of cortisol in saliva. The relation between salivary and serum cortisol concentrations was tested. Reference ranges at 8 AM and 10 PM for the salivary cortisol assay were established from 195 healthy subjects. Salivary cortisol concentrations were tested in relation to serum cortisol in estimating adrenocortical function during endocrine dynamic function tests in 37 patients and 13 healthy controls. In testing salivary cortisol as a marker for stress for fieldwork use, a screening study was performed on 66 male rescue workers. Salivary cortisol at 8 AM and 10 PM and serum prolactin were determined and general psychological health and posttraumatic psychological distress were estimated with the self-rating scales General Health Questionnaire, Impact of Event Scale and Posttraumatic Symptom Scale. These scales were used in the second phase of the thesis. Three applied follow-up studies were performed with sampling of salivary cortisol and self-ratings: (a) a study of 31 UN-soldiers five days, two and nine months after a mine accident; (b) a study of 145 UN-soldiers before, at return, and two and six month after a six month mission. (c) a study of 101 UN-soldiers six and twelve months after a six month mission with severe combat exposure.

    The results from the present thesis indicate that the modified method of salivary cortisol determination possesses sufficient precision, accuracy, sample storage stability and procedural advantages for laboratory, clinical and field application. Moreover, it possesses moderate predictive information and moderate to high concurrent validity as a biochemical marker for posttraumatic psychological distress.

  • 32.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Eriksson, Thomas E.
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Thorell, Lars-Håkan
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Salivary cortisol, posttraumatic stress symptoms, and general health in the acute phase and during 9-month follow-up2001In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 50, no 12, 986-993 p.Article in journal (Refereed)
    Abstract [en]

    Background: Because traumatic events are unpredictable, there are few studies of psychobiological states immediately following such events. Our study aimed to determine the relation of salivary cortisol to psychologic distress immediately after a traumatic event and then during follow-up.

    Methods: Measurement of morning and evening salivary cortisol and ratings of psychologic distress (using the Impact of Events Scale [IES], the Post Traumatic Symptom Scale, and the General Health Questionnaire) were performed with 31 United Nations soldiers at three time points—5 days and 2 and 9 months—following a mine accident in Lebanon.

    Results: Five days after the accident, 15 subjects reported substantial posttraumatic distress according to the IES, as well as significantly lower morning and higher evening cortisol levels compared with the low-impact group. Within 9 months, the posttraumatic distress of the high-impact group was reduced, accompanied by an increase in morning and a decrease in evening cortisol levels. There were significant relationships between evening cortisol and all rating scales at the first and third time points.

    Conclusions: Subclinical posttraumatic stress following an adverse event can be measured biologically via salivary cortisol levels soon after the event.

  • 33.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Eriksson, Thomas E.
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Thorell, Lars-Håkan
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Twelve Months Follow-up of Salivary Cortisol in Relation to Psychological Distress and General Health in Swedish UN-personnel after Severe Combat Exposure during Six Months Mission in BosniaManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Our group has presented evidence of relationships between salivary cortisol levels and psychological distress before, during and after trauma-related stress. The aim of the present study was to confirm the part of evidence of relationships between salivary cortisol and posttraumatic distress and their change over time.

    Methods: Salivary cortisol levels at 8 AM and 10 PM and self-ratings were collected from 106 subjects six and twelve months after a six months UNmission in Bosnia. The rating instruments were the "Impact of Event Scale" (IES), the "Post Traumatic Symptom Scale" and the "General Health Questionnaire".

    Results: Significant statistical interactions were found between changes in mean cortisol levels and IES scores over time. Decreasing evening cortisol levels over time were significantly related to decreasing IES scores and vice versa. Morning cortisol levels showed negative, and evening cortisol positive correlations with all rating scores.

    Conclusions: The evidence from previous studies on trauma related stress, that salivary cortisol is related to the development of posttraumatic stress reactions, the morning cortisol in reverse (negative) direction to that (positive) of evening cortisol, were confirmed.

  • 34.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Eriksson, Thomas E.
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Thorell, Lars-Håkan
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Pre-trauma Salivary Cortisol Levels and General Health Ratings in Relation to Post-trauma Changes in Cortisol and Psychological Distress after UN-service in BosniaManuscript (preprint) (Other academic)
    Abstract [en]

    Background: The psychobiology of post-traumatic distress is known to some extent, however the pre-trauma psychobiology is not. The aims of the present study were to relate pre- and post-trauma salivary cortisol levels and general health to post-traumatic distress in a Swedish UN-battalion in Bosnia.

    Methods: Salivary 8 AM and I 0 PM cortisol levels and "General Health Questionnaire" ratings were collected from 145 subjects before the six months' mission, at return and two and six months after mission. During follow-up, the ratings were extended by the "Impact of Events Scale" (IES) and "Post Traumatic Symptom Scale".

    Results: Low pre-trauma morning and evening salivary cortisol levels were statistically significantly related to high scores in all rating scales six months after mission and to increasing IES scores during follow-up. Low morning and high evening post-trauma salivary cortisol levels were related to high ratings of psychological distress six months after mission

    Conclusions: Pre-trauma salivary cortisol levels seem to be related to posttrauma psychological distress, however not to the extent that salivary cortisol levels in a simple way could be used for predictive screening.

  • 35.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Eriksson, Thomas
    Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
    Holm, Ann-Charlotte
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Lundin, Tom
    Department of Psychiatry, Uppsala Academic Hospital, Uppsala University, Uppsala (TL), Sweden.
    Salivary cortisol and serum prolactin in relation to stress rating scales in a group of rescue workers1999In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 46, no 6, 850-855 p.Article in journal (Refereed)
    Abstract [en]

    Background: Rescue service personnel are often exposed to traumatic events as part of their occupation, and higher prevalence rates of psychiatric illness have been found among this group.

    Methods: In 65 rescue workers, salivary cortisol at 8 am and 10 pm and serum prolactin at 8 am were related to the psychiatric self-rating scale General Health Questionnaire (GHQ-28) measuring psychiatric health, and the Impact of Events Scale (IES) and Post Traumatic Symptom Scale (PTSS) measuring posttraumatic symptoms.

    Results: Seventeen percent of the study population scored above the GHQ-28 cut-off limit but none scored beyond the cut-off limit in the IES and PTSS questionnaires. Salivary cortisol concentration at 10 pm correlated with statistical significance to anxiety (p < .005) and depressive symptoms (p < .01) measured with GHQ-28, as well as to posttraumatic symptoms, with avoidance behavior measured with IES (p < .01) and PTSS (p < .005). Two of the rescue workers were followed over time with the same sampling procedure after a major rescue commission.

    Conclusions: The correlation between evening salivary cortisol and anxiety, depressiveness, and posttraumatic avoidance symptoms indicates that these parameters can be used in screening and follow-up after traumatic stress events.

  • 36.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion.
    Holm, AC
    Eriksson, TE
    Lundin, T
    Linkoping Univ, Fac Hlth Sci, Dept Biomed & Surg, Ctr Clin Chem, S-58185 Linkoping, Sweden.
    Thorell, Lars-Håkan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Psychiatry . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Salivary cortisol and posttraumatic stress reactions methodological and applied studies before and after trauma2002In: International Journal of Psychophysiology, ISSN 0167-8760, Vol. 45, no 1-2, 89-89 p.Conference paper (Other academic)
  • 37.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Karlberg, Bengt E.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Holm, Ann-Charlotte
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Salivary cortisol: an alternative to serum cortisol determinations in dynamic function tests1998In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, Vol. 36, no 4, 215-222 p.Article in journal (Refereed)
    Abstract [en]

    Salivary cortisol was measured as an alternative to serum cortisol as a marker for adrenocortical function following insulin tolerance test, corticotropin-releasing-hormone stimulation and adreno-corticotrophic hormone stimulation. During insulin tolerance test and corticotropin-releasing-hormone stimulation adreno-corticotrophic hormone was also measured. The tests were performed on healthy control subjects as well as on patients under investigation for various disturbances in the hypothalamic-pituitary-adrenocortical axis (insulin tolerance test: 3 controls on two occasions and 14 patients; corticotropin-releasing-hormone stimulation: 4 controls and 18 patients; adreno-corticotrophic hormone stimulation: 6 controls and 10 patients). Five patients underwent both insulin tolerance test and corticotropin-releasing-hormone stimulation. Using criteria for adequate cortisol response in serum, the patients were classified as good or poor responders. In 42 of the 45 tests performed the same conclusion as to cortisol status was drawn when based on serum and salivary cortisol responses. In healthy subjects and good responders the mean cortisol relative increase was greater in saliva than in serum in all three tests (p < 0.05). Characteristic of the results for the insulin tolerance test was a significant initial mean decrease (p < 0.05), not found in serum, and the highest observed salivary cortisol value was delayed for at least 30 minutes compared to that in serum. Plasma adreno-corticotrophic hormone correlated significantly with the cortisol concentrations determined 15 minutes later in serum (r = 0.54–0.64) and in saliva (r = 0.76–0.85). The more pronounced cortisol response in saliva than in serum and its closer correlation with adreno-corticotrophic hormone offer advantages over serum cortisol, suggesting salivary cortisol measurement may be used as an alternative parameter in dynamic endocrine tets.

  • 38.
    Aardal-Eriksson, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Mobäck, Caroline
    Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Jakobsson, Sandra
    Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Germany.
    Hoffmann, Johannes J. M. L.
    Abbott GmbH and Co KG, Germany.
    Iron depletion in blood donors - Have extended erythrocyte and reticulocyte parameters diagnostic utility?2015In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 53, no 1, 76-81 p.Article in journal (Refereed)
    Abstract [en]

    Background: Blood donation is associated with iron depletion, but donor iron status is not usually investigated, as such tests are cumbersome and costly. It would therefore be desirable to have simple, fast and inexpensive tests that give information on a donors risk of developing iron depletion. In a pilot study we investigated whether novel erythrocyte and reticulocyte parameters can serve this goal. Methods: In regular blood donors extended red cell parameters were measured using the Abbott CELL-DYN Sapphire hematology analyzer and conventional biochemical tests of iron status. Donors were compared with a regionally matched group of non-donating controls. Results: In the controls, the reference ranges of extended RBC parameters were well comparable to published data. Donors had significantly more microcytic RBC than controls (median 0.9 vs 0.6%), lower serum ferritin concentration (median 43 vs 91 mg/L) and higher soluble transferrin receptor/ferritin index (median 1.60 vs 1.27). Overall 18-28% of the donors were iron depleted. Moreover, 3.3% of donors had iron-restricted erythropoiesis. Microcytic RBC and reticulocyte mean cell hemoglobin content predicted iron depletion with 70% and 64% sensitivities and specificities of 72% and 78%, respectively. When combined these two parameters increased the sensitivity to 82%. Conclusions: Our results in Swedish blood donors confirm a high prevalence of iron depletion, despite iron supplementation used by about half of the donors. Microcytic RBC and MCHr appeared to be helpful in identifying iron-depleted donors, who might benefit from iron supplementation. We recommend larger prospective investigations in order to confirm and extend the findings of this pilot study. (C) 2015 Elsevier Ltd. All rights reserved.

  • 39. Aare, Magnus
    et al.
    von Holst, Hans
    KTH, School of Technology and Health (STH), Neuronic Engineering.
    Injuries from motorcycle- and moped crashes in Sweden from 1987 to 1999.2003In: Injury control and safety promotion, ISSN 1566-0974, Vol. 10, no 3, 131-8 p.Article in journal (Refereed)
    Abstract [en]

    The objective of this paper is to study injuries from motorcycle and moped crashes in Sweden from 1987 to 1999. Databases at the National Board for Health and Welfare and codes from both ICD9 and ICD10 systems were used, including patterns of age, gender, E-code and type of injury. Length of hospital stay, type of injuries and trends over time was evaluated. To get a more detailed picture of the age distribution, type of vehicle used and number of killed, data from the Swedish National Road Administration were also used. In Sweden, 27,122 individuals received in-patient care due to motorcycle and moped injuries between 1987 and 1999. The motorcycle and moped injury rate was reduced in the second half of the studied period and so were the total days of treatment per year. Males had eight times the incidence of injuries compared to females. Riders under the age of 26 and in particular those at an age of 15 had the highest incidence rate. Head injuries were the most frequent diagnosis, followed by fractures to the lower limbs. Concussion was the most frequent head injury. Focal and diffuse brain injuries combined showed the same frequency as concussion. It is concluded that more preventative strategies must be presented before the injury rate can be reduced.

  • 40.
    Aare, Sudhakar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Ochala, Julien
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Norman, Holly S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Radell, Peter
    Eriksson, Lars I
    Göransson, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Chen, Yi-Wen
    Hoffman, Eric P
    Larsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model2011In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 43, no 24, 1334-1350 p.Article in journal (Refereed)
    Abstract [en]

    Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients which is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents (NMBA), corticosteroids (CS) and sepsis for five days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after five days exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to five days exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements and sarcomeric proteins underlying the relative sparing of cranial versus spinal nerve innervated muscles during exposure to the ICU intervention.

  • 41.
    Aare, Sudhakar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Radell, Peter
    Department of anesthesiology, Karolinska Inistitute.
    Eriksson, Lars
    Department of anesthesiology, Karolinska Inistitute.
    Akkad, Hazem
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Chen, Yi-Wen
    Research center for genetic medicine.
    Hoffman, Eric
    Research center for genetic medicine.
    Lars, Larsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Effects of corticosteroids in the development of limb muscle weakness in a porcine intensive care unit model2013In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 45, no 8, 312-320 p.Article in journal (Refereed)
    Abstract [en]

    Severe muscle wasting is a debilitating condition in critically ill intensive care unit (ICU) patients, characterized by general muscle weakness and dysfunction, resulting in a prolonged mobilization, delayed weaning from the ventilator and a decreased quality of life post-ICU. The mechanisms underlying limbmuscle weakness in ICU patients are complex and involve the impact of primary disease, but also factors common to critically ill ICU patients such as sepsis, mechanical ventilation (MV), immobilization and systemic administration of corticosteroids (CS).  These factors may have additive negative effects on skeletal muscle structure and function, but their respective role alone remain unknown. The primary aim of this study was to examine how CS administration potentiates ventilator and immobilization-related limb muscle dysfunction at the gene level. Comparing biceps femoris gene expression in pigs exposed to MV and CS for five days with only MV pigs for the same duration of time showed a distinct deregulation of 186 genes using microarray. Surprisingly, the decreased force-generation capacity at the single muscle fiber reported in response to the addition of CS administration in mechanically ventilated and immobilized pigs was not associated with an additional up-regulation of proteolytic pathways. On the other hand, an altered expression of genes regulating kinase activity, cell cycle, transcription, channel regulation, oxidative stress response , cytoskeletal, sarcomeric and heat shock protein as well as protein synthesis at the translational level appear to play an additive deleterious role for the  limb muscle weakness in immobilized ICU patients.

     

  • 42.
    Aare, Sudhakar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Radell, Peter
    Department of anesthesiology, Karolinska Inistitute.
    Eriksson, Lars
    Department of anesthesiology, Karolinska Inistitute.
    Chen, Yi-Wen
    Research center for genetic medicine.
    Hoffman, Eric P
    Research center for genetic medicine.
    Larsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    The role of sepsis in the development of limb muscle weakness in a porcine intensive care unit model2012In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 44, no 18, 865-877 p.Article in journal (Refereed)
    Abstract [en]

    Severe muscle wasting and loss of muscle function in critically ill mechanically ventilated intensive care unit (ICU) patients have significant negative consequences on their recovery and rehabilitation that persist long after their hospital discharge; moreover the underlying mechanisms are unclear. Mechanical ventilation (MV) and immobilization-induced modifications play an important role in these consequences, including endotoxin induced sepsis. The present study aims to investigate how sepsis aggravates ventilator and immobilization-related limb muscle dysfunction. Hence, biceps femoris muscle gene expression was investigated in pigs exposed to ICU intervention, i.e., immobilization, sedation, and MV, alone or in combination with sepsis for five days. In previous studies, we have shown that ICU intervention alone or in combination with sepsis did not affect muscle fiber size on day 5, but a significant decrease was observed in single fiber maximal force normalized to cross-sectional area (specific force) when sepsis was added to the ICU intervention. According to microarray data, the addition of sepsis to the ICU intervention induced a deregulation of more than 500 genes, such as an increased expression of genes involved in chemokine activity, kinase activity and transcriptional regulation. Genes involved in the regulation of the oxidative stress response, cytoskeletal/sarcomeric and heat shock proteins were on the other hand down-regulated when sepsis was added to the ICU intervention. Thus, sepsis has a significant negative effect on muscle function in critically ill ICU patients and chemokine activity and heat shock protein genes are forwarded to play an instrumental role in this specific muscle wasting condition.

  • 43.
    Aare, Sudhakar Reddy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Intensive Care Unit Muscle Wasting: Skeletal Muscle Phenotype and Underlying Molecular Mechanisms2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Acute quadriplegic myopathy (AQM), or critical illness myopathy, is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients characterized by generalized muscle wasting and weakness of limb and trunk muscles. A preferential loss of the thick filament protein myosin is considered pathognomonic of this disorder, but the myosin loss is observed relatively late during the disease progression. In attempt to explore the potential role of factors considered triggering AQM in sedated mechanically ventilated (MV) ICU patients, we have studied the early effects, prior to the myosin loss, of neuromuscular blockade (NMB), corticosteroids (CS) and sepsis separate or in combination in a porcine experimental ICU model. Specific interest has been focused on skeletal muscle gene/protein expression and regulation of muscle contraction at the muscle fiber level. This project aims at improving our understanding of the molecular mechanisms underlying muscle specific differences in response to the ICU intervention and the role played by the different triggering factors.

    The sparing of masticatory muscle fiber function was coupled to an up-regulation of heat shock protein genes and down-regulation of myostatin are suggested to be key factors in the relative sparing of masticatory muscles. Up-regulation of chemokine activity genes and down-regulation of heat shock protein genes play a significant role in the limb muscle dysfunction associated with sepsis. The effects of corticosteroids in the development of limb muscle weakness reveals up-regulation of kinase activity and transcriptional regulation genes and the down-regulation of heat shock protein, sarcomeric, cytoskeletal and oxidative stress responsive genes. In contrast to limb and craniofacial muscles, the respiratory diaphragm muscle responded differently to the different triggering factors. MV itself appears to play a major role for the diaphragm muscle dysfunction. By targeting these genes, future experiments can give an insight into the development of innovative treatments expected at protecting muscle mass and function in critically ill ICU patients.

  • 44. Aareleid, Tiiu
    et al.
    Leinsalu, Mall
    Rahu, Mati
    Baburin, Aleksei
    Lung cancer in Estonia in 1968-87: time trends and public health implications.1994In: European Journal of Cancer Prevention, ISSN 0959-8278, E-ISSN 1473-5709, Vol. 3, no 5, 419-425 p.Article in journal (Refereed)
    Abstract [en]

    Changes in lung cancer incidence and mortality in Estonia were studied for 20 years (1968-87). A steady upward trend was observed for men and women. The 1983-87/1968-72 age-standardized incidence rate ratio was 1.22 (95% confidence interval (CI) 1.15-1.29) in men and 1.34 (95% CI 1.16-1.54) in women. The corresponding mortality rate ratio was 1.26 (95% CI 1.18-1.34) in men and 1.35 (95% CI 1.16-1.57) in women. The age-specific incidence and mortality rates increased clearly towards the younger birth cohorts. For men and women, the increase was most evident for the age group 45-64 years. In women there was a more rapid increase in incidence and mortality than in men. It may be a result of a substantial increase of tobacco smoking, particularly among women, after the World War II. The high and still rising occurrence of lung cancer is closely related to the high prevalence of smoking; in addition, high tar yields in domestic cigarettes could have been responsible for an elevated lung cancer risk during the past decades. There is not tobacco control programme in Estonia, and existing legislation and regulations do not defend the non-smoking population.

  • 45.
    Aarenstrup, Sophie
    et al.
    Kristianstad University, School of Education and Environment.
    Ekberg, Oscar
    Kristianstad University, School of Education and Environment.
    Matglädje: Möjliga metoder till att finna matglädjen vid ätstörningar2012Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Eating disorders are a growing public health concern which requires more attention and research to increase the understanding and prevention of eating disorders. This paper focuses on eating disorders and its relation to the joy of food. It is very important to find joy for food when suffering from an eating disorder to achieve a healthier life and healthier thinking around food and the body. This paper has examined possible methods that can be used for treating people with eating disorders to enjoy food. The study was conducted at Capio Anorexia Center in Malmö, a daycare clinic for eating disorders, and the study was focused on how the staff works to help patients find joy for food during treatment, and how they work to express food in a positive way to their patients.

    Methods: Literature studies were carried out before and after the study at Capio Anorexia Center. Qualitative half structured interviews were also carried out with two of the staff at Capio Anorexia Center, and with a dietitian and an anonymous person who has suffered from an eating disorder and received treatment. Three of the interviews were conducted with sound recording and the other one was conducted via email. Each interview lasted about 45 minutes. The interviews were compiled by first writing of the recorded interviews and then the answers for each interview were categorized to relevant fields. An analysis and comparison of these interviews to various literatures like books, reports, scientific papers and internet sources related to enjoying food and eating disorders were also carried out.

    Results: Eleven methods were found that may be useful to find joy for food both in treatment and outside of treatment for those who need support: daring, educational meals, eating regularly, varied and plan meals, cook and serve appealing meals, mindfulness and mindfulness eating, eating environment and social importance when eating, nutritional therapy, the “sapere-method”, eating slow and relaxed, the use of vodcast during meals and to keep out myths, dieting and beauty ideals.

    Conclusions: Eleven possible methods that may be useful to find joy for food have been found. This by preliminary studies with literature, a study at Capio Anorexia Center and interviews, and also by analyzing and comparing the interviews with literature related to eating disorders and enjoying food. The eleven methods described may be useful when regaining joy for food and a healthier thinking when it comes to food and meal situations. An important step in recovering from an eating disorder is to find pleasure when eating; therefore these methods can be possible tools to help people with eating disorders to find the joy for food. However, to reach a healthy life free from an eating disorder these methods described in this paper has to be combined with a variety of other therapies, because it is also important to work with self-esteem, self-confidence, and other symptoms and problems of the eating disorder.

  • 46.
    Aarnio, Pauliina
    et al.
    Dept for International Health, Medical School, University of Tampere, Finland.
    Olsson, Pia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Chimbiri, Agnes
    Kulmala, Teija
    Male involvement in antenatal HIV counseling and testing: exploring men's perceptions in rural Malawi2009In: AIDS Care, ISSN 0954-0121, E-ISSN 1360-0451, Vol. 21, no 12, 1537-1546 p.Article in journal (Refereed)
    Abstract [en]

    Antenatal care can act as an excellent tool to improve access to HIV counseling and testing services. This paper investigates an issue that may weaken its potential, namely lack of male involvement. We explored married men's perceptions of HIV in pregnancy and male involvement in antenatal HIV testing and counseling in Southern Malawi through 11 focus group discussions and a cross-sectional survey (n=388). The main findings were that men were largely unaware of available antenatal HIV testing and counseling services, and perceived it overall problematic to attend female-oriented health care. Most men supported provision of antenatal HIV testing. They perceived husbands to participate in the process indirectly through spousal communication, being faithful during pregnancy, and supporting the wife if found HIV-positive. Involvement of husbands was compromised by men's reluctance to learn their HIV status and the threat that HIV poses on marriage. Men stressed the importance of prior spousal agreement of antenatal HIV testing and considered HIV testing without their consent a valid reason for divorce. We suggest that male involvement in antenatal HIV testing requires refocusing of information and health services to include men. To avoid negative social outcomes for women, comprehensive and early involvement of men is essential.

  • 47.
    Aaro, Martina
    Örebro University, School of Medicine, Örebro University, Sweden.
    Antibiotic Prophylaxis in Head and Neck Oncologic Surgeryat Örebro University Hospital (USÖ)2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 48.
    Aaro, Martina
    Örebro University, School of Medical Sciences.
    Polypharmacy and Inappropriate Drug Use among Elderly Patients admitted to a Short-Term Nursing Home in Örebro2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 49.
    Aarts, B.
    et al.
    Netherlands Forensic Institute, Biological Traces and DNA, The Hague, Netherlands.
    Kokshoorn, B.
    Netherlands Forensic Institute, Biological Traces and DNA, The Hague, Netherlands.
    Mc Kenna, L.G.
    Forensic Science Ireland, DNA department, Dublin, Ireland.
    Drotz, W.
    Swedish National Forensic Centre, DNA department, Linköping, Sweden.
    Ansell, Ricky
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Swedish National Forensic Centre, DNA department, Linköping, Sweden.
    van Oorschot, R.A.
    Office of the Chief Forensic Scientist, Victoria Police Forensic Services Department, Macleod- Victoria, Australia.
    Kloosterman, A.D.
    Netherlands Forensic Institute, Biological Traces and DNA, The Hague, Netherlands.
    DNActivity: International cooperation in activity level interpretation of forensic DNA evidence.2015In: Abstract book, 7th European Academy of Forensic Science, EAFS, Prag, Tjeckien, 2015., 2015, 555- p.Conference paper (Other academic)
    Abstract [en]

    Questions posed to expert witnesses by the legal community and the courts are expanding to include not just those relating to source level (i.e. ‘who is the donor of the trace?’) but also those relating to activitity level (i.e. ‘how did the DNA get there?’). The answers to these questions are usually formulated as the probability of the evidence under alternative scenarios. As activity level questions are part of investigative and legal considerations it is of paramount importance that expert witnesses are provided with knowledge and tools to address these questions.

    To answer such questions within a probabilistic framework, empirical data is needed to estimate probabilities of transfer, persistence and recovery of DNA as well as background levels of DNA on everyday objects. There is a paucity of empirical data on these topics, but the number of studies is increasing both through in-house experiments and experimental data published in international scientific journals.

    Laboratories that conduct such studies all use different experimental setups, trace recovery strategies and techniques and DNA analysis systems and equipment. It is essential for the forensic genetics community in general to establish whether the data generated by different labs are in concordance, and can therefore be readily used by the forensic community.

    Moreover, if existing data and data generated from future experiments are made available to the (forensic) community, knowledge is needed on the key factors that underlie potential interlaboratory variation.

    The aims and objectives of this ENFSI Monopoly 2013 project are to conduct a study of methodologies and data from different laboratories and to assess the comparability of the scientific data on transfer, persistence and recovery of DNA. This comparison will allow us to identify key factors that underlie potential variation. This information will be used to setup guidelines to enable sharing and database-storage of relevant scientific

    data. This will improve the ability of forensic scientists and other professionals of the Criminal Justice System to give evidence-based answers to questions that relate to the activity level of the crime under investigation.

  • 50.
    Aarts, Clara
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Exclusive breastfeeding-Does it make a difference?: A longitudinal, prospective study of daily feeding practices, health and growth in a sample of Swedish infants2001Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The concept of exclusive breastfeeding in relation to daily feeding practices and to health and growth of infants in an affluent society was examined. In a descriptive longitudinal prospective study 506 mother-infant pairs were followed from birth through the greater part of the first year. Feeding was recorded daily, and health and growth were recorded fortnightly.

    Large individual variations were seen in breastfeeding patterns. A wide discrepancy between the exclusive breastfeeding rates obtained from "current status" data and data "since birth" was found.

    Using a strict definition of exclusive breastfeeding from birth and taking into account the reasons for giving complementary feeding, the study showed that many exclusively breastfed infants had infections early in life, the incidence of which increased with age, despite continuation of exclusive breastfeeding. However, truly exclusively breastfed infants seem less likely to suffer infections than infants who receive formula in addition to breast milk. Increasing formula use was associated with an increasing likelihood of suffering respiratory illnesses. The growth of exclusively breastfed infants was similar to that of infants who were not exclusively breastfed.

    The health of newborn infants during the first year of life was associated with factors other than feeding practices alone. Some of these factors may be prenatal, since increasing birth weight was associated with an increasing likelihood of having respiratory symptoms, even in exclusively breastfed infants. However, exclusive breastfeeding was shown to be beneficial for the health of the infant even in an affluent society.

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