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  • 51.
    Midhagen, Gunnar
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology.
    Adult Coeliac Disease in Clinical Practice2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Coeliac disease (CD) is considered to be the result of a complex interplay of intrinsic (genetic) factors and variable extrinsic (environmental) factors. The complex background of CD explains its wide spectrum of clinical manifestations. For a very long time CD was considered more or less a disease of childhood, which was extremely rare in adults. Nowadays we know that CD is one of the most common food intolerance disorders.

    An epidemiological study of CD in a geographically defined area of Sweden (Paper1) showed a prevalence of 95.5/ 100 000 inhabitants. Among the associated diseases an especially high incidence of associated thyroid disease, 10.8% was observed.

    In a fifteen-year cohort follow up study of all CD-patients residing in the counties of Örebro and Linköping (Paper 2) the total mortality was increased with 38% (SMR 1.38 95% C.I. 0.31-0.83). This was mainly explained by a 48% increased death rate in ischemic heart disease, significant in patients over 65 years (SMR 1.58 95% C.I. 1.00-2.06). However, there was a 47 % lower risk of all malignancies (SIR 0.53 95% C.I. 0.31-0.83).

    A cohort of 22 consecutively biopsy-proven adult CD patients (Paper 3), were followed in respect of antibody titres from diagnosis and after 1, 3, 6, and 12 months on a gluten free diet (GFD). All antibody titres fell sharply within one month. Thus excluding a CD diagnosis serologically on a patient who has initiated a GFD by herself is not to recommend.

    In another cohort with CD patients (Paper IV) who were diagnosed 8-12 years earlier recommended and who were recommended, the reliability of diet history, serological and biochemical markers to predict the appearance of the small intestinal mucosa were analysed (Paper IV). The history of a strict GFD gave a predictive value of 88% of a mucosa in remission. The values of serological tests (AGA, EmA and tTG) to predict a mucosa in remission were 93% for all.

    In CD patients in remission gastro-intestinal symptoms were evaluated with the GSRS questionnaire. Subjects with CD reported significantly more GI-symptoms than a general population sample (p<0.01). This was particularly true for women with CD who scored worse than female controls .By contrast men with CD reported no more symptoms than male controls.

  • 52.
    Moore, Jason W.
    Umeå University, Faculty of Arts, Department of historical, philosophical and religious studies.
    Environmental crises and the metabolic rift in world-historical perspective2000In: Organization & environment, ISSN 1086-0266, E-ISSN 1552-7417, Vol. 13, no 2, 123-157 p.Article in journal (Refereed)
    Abstract [en]

    This article proposes a new theoretical framework to study the dialectic of capital and nature over the longue durée of world capitalism. The author proposes that today’s global ecological crisis has its roots in the transition to capitalism during the long sixteenth century. The emergence of capitalism marked not only a decisive shift in the arenas of politics, economy, and society, but a fundamental reorganization of world ecology, characterized by a “metabolic rift,” a progressively deepening rupture in the nutrient cycling between the country and the city. Building upon the historical political economy of Marx, Foster, Arrighi, and Wallerstein, the author proposes a new research agenda organized around the concept of systemic cycles of agro-ecological transformation. This agenda aims at discerning the ways in which capitalism’s relationship to nature developed discontinuously over time as recurrent ecological crises have formed a decisive moment of world capitalist crisis, forcing successive waves of restructuring over long historical time.

  • 53.
    Mustafa, Mudassir Imran
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media.
    Design Principles for Data Export: Action Design Research in U-CARE2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In this thesis, we report the findings of designing data export functionality in Uppsala University Psychosocial Care Program (U-CARE) at Uppsala University. The aim of this thesis was to explore the design space for generic data export functionality in data centric clinical research applications for data analysis. This was attained by the construction and evaluation of a prototype for a data-centric clinical research application. For this purpose Action Design Research (ADR) was conducted, situated in the domain of clinical research. The results consist of a set of design principles expressing key aspects needed to address when designing data export functionality. The artifacts derived from the development and evaluation process each one constitutes an example of how to design for data export functionality of this kind.

  • 54.
    Nilsson, Andreas
    Örebro University, School of Health and Medical Sciences.
    Physical activity assessed by accelerometry in children2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Physical activity (PA) is likely to constitute an important aspect of health-related behaviour in growing children. However, the knowledge on levels and patterns of PA in children is limited, due to the difficulty of precisely measuring this complex behaviour in normal daily living. Information on variables that significantly contributes to the variability in PA patterns is warranted as it may inform strategies for promoting physically active lifestyles in school-age youth. The overall purpose of the present studies was to increase the knowledge about the use of accelerometry when assessing PA in children, and examine sources of variability in objectively assessed PA behaviour in children. The study samples included 1954 nine- and 15-year-old children from four geographical locations in Europe (Norway, Denmark, Estonia and Portugal), and additionally 16 Swedish seven-year-old boys and girls. PA was assessed by the MTI accelerometer during free-living conditions, including both weekdays and weekend days. A part of the PA assessment was conducted using different time sampling intervals (epochs). Predictions of estimates of daily energy expenditure from accelerometer output were calculated using previously published equations. Potential correlates of PA behaviour were assessed by self-report. The main findings were; a) the epoch setting had a significant effect when interpreting time spent at higher intensities of PA in young children, b) predicted energy expenditure differed substantially between equations, c) between- and within-day differences in overall levels of PA, time spent at moderate-to-vigorous intensity physical activity and time spent sedentary differed between age, gender and geographical location, d) outdoor play and sports participation were differentially associated with objectively measured PA in 9- and 15-year-old children. It is concluded that the sporadic nature of children’s physical activity require very short epoch settings for detecting high intensity PA, and that different published equations for estimations of daily energy expenditure cannot be used interchangeably. The interpretations of average energy expenditure from available equations should be made with caution. Based on a large sample of children of different ages, weekend days and leisure time during weekdays seem appropriate targets when promoting PA in order to increase the proportion of children achieving current recommendations on health enhancing PA. Further, significant correlates of PA behaviour dependent on age group are presented, which should be considered when planning interventions for promoting PA in school-age youth.

  • 55.
    Nilsson, Staffan
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, East County Primary Health Care.
    Chest pain and ischemic heart disease: Diagnosis and management in primary health care2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background and aims. In patients consulting for chest pain, it is of great importance to evaluate the possibility of ischemic heart disease (IHD). The aims in this thesis were to investigate the accuracy of the general practitioners’ clinical assessments and the applicability of exercise testing and myocardial perfusion scintigraphy (MPS) in patients consulting for chest pain in primary care.

    Statins are known to prevent IHD. A further aim was therefore to investigate if a relation could be detected on a population basis between the use of statins and the morbidity of acute myocardial infarction (AMI).

    Methods. All patients from 20 to 79 years, consulting for a new episode of chest pain in three primary health care centres, were included during almost two years from 1998 to 2000. The patients were managed according to the clinical evaluation. The presence of IHD was excluded either by clinical examination only, or if stable IHD was in question, by exercise testing and if the exercise test was inconclusive by an additional MPS. If unstable IHD or myocardial infarction was suspected, referral for emergency hospital examination was made.

    Correlations between statin sales and the morbidity of AMI in Sweden’s municipalities were analysed in an ecological, register based study. Adjustment was made for sales of antidiabetics, socio-economic deprivation indexes and geographic coordinates.

    Results. Consultations for chest pain represented 1.5% of all consultations in the ages 20 to 79 and were made by 554 patients. In 281 patients IHD was excluded by clinical examination only. In 208 patients stable IHD and in 65 unstable IHD was in question. Four patients (1.4%) evaluated as not having IHD, were diagnosed with angina pectoris or AMI within three months. Exercise testing was performed in 191 patients and revealed no IHD in 134 and IHD in 14 patients. In 43 patients the exercise test results were equivocal. Thirty-nine of these patients underwent MPS, which showed no IHD in 20 and IHD in 19 of the patients.

    In a follow up almost six years later, neither mortality rate nor prevalence of IHD differed significantly between the 384 study patients evaluated not to have IHD and the population controls.

    Statin sales and AMI-incidence or mortality showed no strong associations from 1998 to 2002.

    Conclusions.

    ·Primary care is an appropriate level of care for ruling out IHD as the cause of chest pain, with sufficient safety and for diagnostics of stable IHD.

    ·Exercise testing and myocardial perfusion scintigraphy are useful procedures when investigating chest pain patients in primary care.

    ·The results indicate that preventive measures other than increased statin treatment should be considered to further decrease AMI-morbidity.

  • 56.
    Norén, Torbjörn
    Örebro University, Department of Clinical Medicine.
    Clostridium difficile: epidemiology and antibiotic resistance2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Clostridium difficile is a spore-forming toxin-producing intestinal bacterium abundant in soils and waters. This pathogen relies on increased growth by a disturbed intestinal microflora and the production of two cytotoxins, toxin A and toxin B, which may cause anything from mild self-limiting C. difficile associated diarrhea (CDAD) to severe and fatal pseudomembranous colitis (PMC). Typically CDAD following antibiotic therapy is due either to overgrowth of endogenous C. difficile or through spores transmitted from the environment. The hospital setting provides frequent antibiotic use and the source of numerous infective spores from CDAD patients, the environment or nursing staff. Today we experience a 10-fold increase of incidence in the US and Canada (1991-2003) apparently due to a current epidemic C. difficile strain (NAP1/027). Current incidence from Canada is estimated to 156/100 000 compared to 50/100 000 in Sweden 1995.

    In the following thesis, investigations of CDAD in Örebro County in central Sweden resulted in the discovery an epidemic nosocomial C. difficile strain (SE17, serogroup C), found to be clindamycin-resistant. The majority of the isolates carried a gene (ermB) related to this resitance. We found an overall incidence during 1999-2000 of 97/100 000 or, if including recurrent episodes, 135/100 000 i.e. more than 100% increase since 1995. The incidence among hospitalized individuals was 1300-fold that in the community and 78% of episodes were classified as hospital-associated. This reflects a 37-fold difference in antibiotic consumption, as well as the predominance of the resistant SE17 hospital-associated strain (22% of hospital isolates compared to 6% of community isolates, p=0.008). Only 10% of the recurrent cases were found to be reinfections indicating that CDAD is mainly caused by endogenous strains and not by hospital transmission.

    Recent reports on failure of standard metronidazole therapy urge for alternative treatment agents and fusidic acid has been proven as effective in the treatment of CDAD. We could verify this, but in both treatment groups we found that persistence of C. difficile isolates post-treatment related to an increased risk of recurrent CDAD compared to the patients who were culture negative at follow-up (p=0.03). Most importantly, 55% of patients with follow-up isolates and who had been treated with fusidic acid, the strains had developed fusidic acid resistance. The corresponding pre-treatment identity of isolate genotype indicated selection of mutants. Relating to the known fusA resistance mechanism in Staphylococcus aureus we used the published sequence for this gene in Clostridium perfringens and found homologous fusA in the sequence of the referent strain C. difficile 630. Comparing fusA of the resistant mutants with the initial wild-type isolates, we identified novel mutations in fusA as the genetic key to fusidic acid resistance in C. difficile.

  • 57.
    Näsberg, Anna
    Mid Sweden University, Faculty of Human Sciences, Department of Health Sciences.
    Kvinnors upplevelser och behov av stöd vid hysterektomi: en litteraturstudie2008Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpStudent thesis
    Abstract [sv]

    Hysterektomi är ett kirurgiskt ingrepp där man opererar bort livmodern på kvinnor där en genital rubbning uppkommit. Syftet med detta arbete var att ge en klarare bild om hur kvinnor upplever detta ingrepp samt hur vårdpersonalen skall bemöta och kunna ge kvinnan stöd om så skulle behövas. Syftet med studien var att genom en litteraturstudie belysa kvinnors upplevelser av hysterektomi samt behov av stöd. En systematisk litteraturstudie gjordes där tretton vetenskapliga studier har inkluderats. Resultatet presenteras i två huvudkategorier, kvinnors upplevelser vid hysterektomi samt kvinnors behov av stöd. Båda kategorierna innefattade underkategorier vilka var livskvalitet, sexualitet, stöd samt information. Resultatet visade på att större delen av kvinnorna som genomgått hysterektomi var nöjda med ingreppet, då ett stort handikapp de dragits med en lång tid lättade eller försvann helt. Kvinnorna saknade information om tiden efter operationen. Information har en stor betydelse av hur kvinnorna upplever hysterektomi. Sammanfattningsvis är det viktigt att sjukvårdspersonal har den kunskapen att ge rätt information vid rätt tillfälle. För att hjälpa de kvinnor som skall genomgå hysterektomi bör vårdpersonalen även kunna vara ett stöd, så att sjukhusvistelsen blir en god upplevelse för dessa kvinnor.

  • 58.
    Oscarsson, Marie
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Healthy women or risk patients?: Non-attendance in a cervical cancer screening program2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Women afflicted with cervical cancer who have the highest morbidity and mortality rates have been the least likely to be screened. The overall aim of this research project was to investigate non-attendance in a cervical cancer screening (CCS) program among women with no registered cervical smear during the previous five years. Both quantitative (I,III) and qualitative methods (II) as well as costeffectiveness analysis (IV) were used in this research project. In Kalmar County women (aged 23-65 years) are invited to CCS every third year. All cervical smears taken both in opportunistic and organised CCS are coordinated in a register called Sympathy. The coverage is 88.4 %. From Sympathy, a random sample of 400 women served as a study group and another 400 women as a control group (III,IV). From the study group, 133 women participated in study I and 14 women in study II. Data was collected by telephone interviews based on a questionnaire (I), qualitative face-to-face interviews (II), questionnaire, promotive efforts and outcome (III), costs and effectiveness (IV). Quantitative data was analysed by descriptive and analytic statistics (I,III), qualitative data was analysed by content analysis. In study IV, cost-effectiveness analysis was used.

    The women believed that CCS was a good idea for all other women, but tended to refer to various circumstances resulting in their own non-attendance. One of the most common reasons for non-attendance was the feeling of being healthy. The women prioritized family and work commitments, and the invitation to attend CCS was sometimes experienced as a stressful disturbance. The feeling of discomfort was related to the gynaecologic examination, or to health care visits in general (I,II). Of 133 women, 120 could consider having a cervical smear taken and their two most common requirements for doing so were to be assured they would be treated in a friendly way (19%) and to find a suitable time (18%) for having the cervical smear. Fifty women wanted to be helped to have a cervical smear taken. Promotive efforts ranged from making a simple telephone call to arranging an appointment time to a combination of promotive efforts including repeated encounters in order to create a trusting relationship with respect to taking the smear. In the study group, 29.5% (n=118) had a registered cervical smear at follow-up compared to 18.5% (n=74) in the control group, (p<0.001) (III). In the study group, the cost per cervical smear taken was 66.87 €, and in the control group it was 16.62 €. The incremental cost per additional cervical smear taken was 151.36 € (IV). In conclusion, women’s reasons for not attending CCS are complex and are influenced by both present and earlier circumstances. In settings with high coverage, further contact in order to promote women’s attendance at CCS seems to be associated with high costs in relation to the number of additional cervical smears taken.

  • 59.
    Peterson, Gunnel
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Neck muscle function in individuals with persistent pain and disability after whiplash injury2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Neck pain and disability are common after whiplash injury. One year after the accident up to 50 % still have symptoms called whiplash associated disorders (WAD). Despite decades of research the cause of persistent pain and disability are largely unknown and effective treatment and diagnostic tools are lacking. Altered neck muscle function may cause pain and disability, and real-time non-invasive methods that investigate both superficial and deep neck muscle function need to be evaluated.

    Aim: The general aim of the work presented in this thesis was to investigate mechanical neck muscle function and evaluate effects of three different exercise interventions related to neck muscle function in individuals with persistent pain and disability after whiplash injury.

    Method: The thesis comprised two studies, reported in four papers. Study A was a prospective randomized controlled trail with 216 participants. The effects of three exercise interventions; neck-specific exercises, neck-specific exercises with behavioral approach and prescription of physical activity were evaluated. Neck muscle endurance, perceived pain following testing, kinesiophobia and satisfaction with treatment were compared between the three groups (paper I). Study B was an experimental case-control study with participants consecutively recruited from the randomized controlled trial. Deformation and deformation rates in the neck muscles were investigated with real-time ultrasound imaging during ten repetitive arm elevations (paper II-IV). To investigate ventral neck muscles, 26 individuals with WAD were compared with 26 healthy controls (paper II). The dorsal neck muscles were investigated in paper III, including 40 individuals with WAD and 40 controls. In total 46 individuals, 23 with WAD and 23 healthy controls were included in paper IV to develop ventral neck muscle interaction models.

    Results: Paper I: Participants in the two neck-specific exercise groups (with and without behavioral approach) showed increased dorsal neck muscle endurance (p = 0.003), decreased pain intensity following testing (p = 0.04) and were more satisfied with treatment (p < 0.001) than participants in the prescribed physical activity group. Kinesiophobia did not significantly differ between groups (p > 0.12).

    Paper II: Deformation and deformation rate showed linear positive relationship between ventral muscle pairs in healthy controls, especially between superficial and deep neck muscles. This relationship was weaker or absent in the WAD group.

    Paper III: The WAD group had higher deformation rates in the deepest dorsal neck muscles during the first and tenth (only women) arm elevations compared to the control group (p < 0.04). Women in the WAD group showed a weaker linear relationship between the two deepest dorsal neck muscles compared to women in the control group.

    Paper IV: The results revealed two different ventral neck muscle models in individuals with WAD and healthy controls (R2Y = 0.72, Q2Y = 0.59). The models were capable to detect different neck muscle interplay in people with WAD.

    Conclusion: Neck-specific exercise intervention with or without a behavioral approach appears to improve neck muscle endurance in individuals with persistent WAD. Decreased pain after the neck muscle endurance test also suggests improved tolerance of load in these two groups. Altered mechanical neck muscle function was revealed in individuals with WAD indicating decreased muscular support for maintain a stable cervical spine during repetitive arm elevations. The results show great promise for improved diagnosis of neck muscle function in WAD.

  • 60.
    Rahman, Mozibur
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Effects of neuroactive steroids on the recombinant GABAA receptor in Xenopus oocyte2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: Neuroactive steroids represent a class of both synthetic and naturally occurring steroids that have an effect on neural function. In addition to classical genomic mechanism by the hormones progesterone, deoxycorticosterone and testosterone 3α-OH metabolites of these hormones enhance GABAA receptor through rapid non-genomic mechanism. The site(s) of action of these neuroactive steroids namely 3α-OH-5α-pregnan-20 one, (3α,5α)-3,21-deoxycorticosterone(3α5α-THDOC) and 5α androstane-3α,17β-diol on GABAA receptor are distinct from that of benzodiazepines and barbiturate binding sites. The modulation site(s) has a well-defined structure activity relationship with a 3α-hydroxy and a 20-ketone configuration in the pregnane molecule required for agonistic action. Pregnenolone sulfate is a noncompetitive GABAA receptor antagonist and inhibit GABA activated Cl- current in an activation dependant manner. 3β-hydroxy A-ring reduced pregnane steroids are also GABAA receptor antagonist and inhibit GABAA receptor function and its potentiation induced by their 3α-diesteromers in a noncompetitive manner.

    Aim: The aim was to investigate if the effect of GABA, pentobarbital antagonism by bicuculline and if the effect of GABA-agonist and antagonist neuroactive steroids including pregnenolone sulfate is dependant on the α-subunits of GABAA receptor. Furthermore, the studies aimed at investigating the binding site of pregnenolone sulfate and if its effect is dependent on γ-subunit. In addition, the inhibitory effect of pregnenolone sulfate and 3β-hydroxy steroids has been characterized. We also wanted to investigate if the neuroactive steroids effect vary between the human and rat recombinant α1β2γ2L receptors and between the long (L) and short (S) variants of γ2-subunit.

    Method: Experiments were performed by the two electrodes voltage-clamp technique using oocytes of Xenopus laevis expressed with recombinant GABAA receptors containing α1, α4 or α5, β2, γ2L and γ2S-subunits.

    Results: There was no difference between the α1, α4 and α5-containing subunits regarding GABA and pentobarbital inhibition by bicuculline. GABA-activated current in the binary αβ was potent than that of ternary αβγ receptor. Unlike Zn2+ effect, inhibition by pregnenolone sulfate on the GABAA receptor is not dependant on the γ-subunit. It is likely that the 2’ residue closest to the N-terminus of the protein at M2 helix on both α1 and β2 subunit are critical to the inhibitory actions of PS and the function of Cl- channels. Point mutation at M2 helix of the β2-subunit (b2A252S) can dramatically reduce the inhibitory effect of PS on the GABAA receptors without affecting the inhibitory properties of 3β-hydroxysteroids. Agonist and antagonist steroids also varied in their efficacy between the human and rat α1β2γ2L receptor. Neuroactive steroids also showed difference between human γ2L and γ2S-containing receptor.

    Conclusions: GABA and pentobarbital antagonism by bicuculline is not dependant on α-subunit. Pregnenolone sulfate binding site is different from that of Zn2+. 3β-hydroxysteroids and pregnenolone sulfate inhibit GABAA receptor through different mechanisms. Neuroactive steroids also differ between species and between the long and short variant of γ- subunit.

  • 61.
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Fat cell insulin resistance: an experimental study focusing on molecular mechanisms in type 2 diabetes2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of the present thesis was to further increase our understanding of mechanisms contributing to and maintaining cellular insulin resistance in type 2 diabetes (T2D). For this reason, the effects of high glucose and insulin levels on glucose transport capacity and insulin signaling, with emphasis on insulin receptor substrate 1 (IRS-1) were assessed in fat cells. Altered levels of IRS-1 have previously been observed in adipose tissue from insulin-resistant and T2D subjects.

    A high glucose level (≥15 mM) for 24 h exerted only a minor impairment on glucose transport capacity in human adipocytes, as opposed to rat adipocytes. However, when combined with a high insulin level (104 µU/ml), basal and insulin-stimulated glucose transport was significantly impaired in both human and rat adipocytes. This was associated with a depletion of IRS-1 and IRS-2 protein levels in rat adipocytes, as a result of post-translational changes and altered gene transcription, respectively. In human adipocytes was only IRS-1 protein levels reduced. The high glucose/high insulin setting achieved maximal impairment of glucose transport within 6 h. Subsequent incubations of rat adipocytes under physiological conditions could partially restore insulin sensitivity. Interestingly, in both human and rat fat cells, decreased levels of IRSs occurred after the establishment of impaired glucose transport, suggesting that the observed depletion of IRSs is a consequence rather than a cause of insulin resistance. Nonetheless, IRS depletion is likely to further aggravate insulin resistance.

    Tyrosine phosphorylation of IRS-1 upon insulin stimulation activates the signaling pathway that mediates glucose transport. Pre-treatment of human adipocytes with high glucose and insulin levels was not associated with any alterations in the total IRS-1 Tyr612 phosphorylation following 10 min insulin stimulation. However, a significant increase in basal Tyr612 phosphorylation was observed. Furthermore, a rise in basal IRS-1 Ser312 phosphorylation was found. This is associated with reduced IRS-1 function and is considered to target IRS-1 to degradation pathways, and thus could potentially explain the observed decrease in IRS-1 protein levels. Our results imply an enhanced activation of insulin’s negative-feedback control mechanism that inhibit IRS-1 function. This could potentially have contributed to the observed impairment of insulin action on glucose transport in these cells. Accordingly, we have also shown that the downstream activation of protein kinase B upon insulin-stimulation is significantly impaired in human adipocytes exposed to the high glucose/high insulin setting, indicating a defect in the signaling pathway mediating glucose transport.

    We also investigated whether there are humoral factors in the circulation of T2D patients that contribute to peripheral insulin resistance. Human adipocytes cultured for 24 h in medium supplemented with 25% serum from T2D subjects, as compared to serum from non-diabetic subjects, displayed significantly reduced insulin-stimulated glucose uptake capacity. The effect could neither be attributed to glucose, insulin, FFA, TNF-α or IL-6 levels in the serum, but other circulating factor(s) seem to be of importance.

    In conclusion, chronic conditions of elevated glucose and/or insulin levels all impair insulin action on glucose turnover, but to different extents. A clear distinction between rat and human fat cells in the response to these different milieus was also observed. Alterations in the function of the key insulin signaling protein IRS-1 might be involved in the mechanisms underlying the impaired glucose uptake capacity. IRS-1 reduction however, occurs after but probably aggravates the existing insulin resistance. The effects of high glucose and/or insulin levels may be of importance in T2D, but additional novel factors present in the circulation of T2D patients seem to contribute to cellular insulin resistance.

  • 62.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Developmental Biology. Linköping University, Faculty of Health Sciences.
    Livestock semen biotechnology and management2012In: Encyclopedia of Life Support Systems (EOLSS): Animal Reproduction in Livestock / [ed] S Astiz Blanco & A Gonzalez Bulnes, Oxford, UK: Eolss Publishers, UNESCO , 2012, 1:a, 1-14 p.Chapter in book (Other academic)
    Abstract [en]

    Modern livestock breeding is basically dependent on the proper use of semen for artificial insemination of females and of other reproductive biotechnologies such as the production of embryos in vitro for embryo transfer. Both these techniques have made possible not only the wide dissemination of genetic material onto breeding populations but also enhanced the selection of best sires, owing to the development of better diagnostic techniques for sperm function and of preservation of seminal material over time. Although use of liquid semen cooled to room temperature, to intermediate temperatures (+16-20°C) or chilled (+5°C) dominates in some livestock species (swine respectively small ruminants), cryopreservation is rule in bovine and it is advancing in other species by the design of new containers, freezing methods and the use of better insemination strategies. Reliable semen diagnostics is absolutely essential to disclose which semen is to be processed/cryopreserved but also to aim determination  of a potential fertilizing capacity in the laboratory, thus saving costs prior to artificial insemination. However, there is a yet no single laboratory method that accurately prognoses fertility in livestock, requiring use of a battery of diagnostic methods. Novel techniques for optimal use of ejaculates (low-dose) and intrauterine deposition of semen throughout species are those management techniques that shall increase our capabilities for better diagnostics/selection of semen/male potential fertility, of cryopreservation techniques and a more rational dissemination of genetics.

  • 63.
    Sanchez Crespo, Alejandro
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Novel computational methods for image analysis and quantification using position sensitive radiation detectors2005Doctoral thesis, monograph (Other academic)
    Abstract [en]

    The major advantage of position sensitive radiation detector systems lies in their ability to non invasively map the regional distribution of the emitted radiation in real-time. Three of such detector systems were studied in this thesis, gamma-cameras, positron cameras and CMOS image sensors. A number of physical factors associated to these detectors degrade the qualitative and quantitative properties of the obtained images. These blurring factors could be divided into two groups. The first group consists of the general degrading factors inherent to the physical interaction processes of radiation with matter, such as scatter and attenuation processes which are common to all three detectors The second group consists of specific factors inherent to the particular radiation detection properties of the used detector which have to be separately studied for each detector system. Therefore, the aim of this thesis was devoted to the development of computational methods to enable quantitative molecular imaging in PET, SPET and in vivo patient dosimetry with CMOS image sensors.

    The first task was to develop a novel quantitative dual isotope method for simultaneous assessments of regional lung ventilation and perfusion using a SPET technique. This method included correction routines for photon scattering, non uniform attenuation at two different photon energies (140 and 392 keV) and organ outline. This quantitative method was validated both with phantom experiments and physiological studies on healthy subjects.

    The second task was to develop and clinically apply a quantitative method for tumour to background activity uptake measurements using planar mammo-scintigraphy, with partial volume compensation.

    The third stage was to produce several computational models to assess the spatial resolution limitations in PET from the positron range, the annihilation photon non-collineairy and the photon depth of interaction.

    Finally, a quantitative image processing method for a CMOS image sensor for applications in ion beam therapy dosimetry was developed.

    From the obtained phantom and physiological results it was concluded that the methodologies developed for the simultaneous measurement of the lung ventilation and perfusion and for the quantification of the tumour malignancy grade in breast carcinoma were both accurate. Further, the obtained models for the influence that the positron range in various human tissues, and the photon emission non-collinearity and depth of interaction have on PET image spatial resolution, could be used both to optimise future PET camera designs and spatial resolution recovery algorithms. Finally, it was shown that the proton fluence rate in a proton therapy beam could be monitored and visualised by using a simple and inexpensive CMOS image sensor.

  • 64.
    Segerdahl, M.
    et al.
    Karolinska Inst, Unit Anesthesia, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Warrén-Stomberg, Margareta
    University of Skövde, School of Life Sciences.
    Rawal, N.
    Örebro Univ Hosp, Dept Anesthesia & Intens Care, Örebro, Sweden .
    Brattwall, M.
    Sahlgrenska Univ Hosp Molndal, Unit Day Care Surg, Gothenburg, Sweden.
    Jakobsson, J.
    Karolinska Inst, Unit Anesthesia, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Clinical practice and routines for day surgery in Sweden2008In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 52, no 1, 117-124 p.Article in journal (Refereed)
    Abstract [en]

    Background: Day surgery is common in paediatric surgical practice. Safe routines including parental and child information in order to optimise care and reduce anxiety are important. Most day surgery units are not specialised in paediatric care, which is why specific paediatric expertise is often lacking.

    Methods: We studied the practice of paediatric day surgery in Sweden by a questionnaire survey sent to all hospitals, obtaining an 88% response rate. Three specific paediatric cases were enquired for in more detail.

    Results: The proportion of paediatric day surgery vs. in-hospital procedures was 46%. Seventy-one out of 88 responding units performed paediatric day surgery. All units had anxiolytic pre-medication as a routine in 1–6-year-olds, and in 7–16-year-olds at 60% of the units. Most units performed circumcision and adenoidectomy, while 33% performed tonsillectomy. Anaesthesia induction was intravenous in older children, and also in 1–6-year-olds at 50% of the units. Parental presence at induction was mandatory. Post-operatively, 93% of units routinely assessed pain. Paracetamol and NSAIDs were the most common analgesics, as monotherapy or combined with rescue medication in the recovery as IV morphine. At 42% of units, take-home bags of analgesics were provided, covering 1–3 days of treatment. Pain was the most frequent complaint on follow-up. Micturition difficulties were common after circumcision, nausea after adenoidectomy and nutrition difficulties after tonsillectomy.

    Conclusions: In Sweden, most day surgery units perform paediatric surgery, most children receive pre-medication, anaesthesia is induced IV and take-home analgesics paracetamol and or NSAIDs are often provided. Still, pain is a common complaint after discharge.

  • 65.
    Sepa, Anneli
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    The Stress Hypothesis: Implications for the induction of diabetes-related autoimmunity in children?2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Second to Finland, Sweden has the world’s highest incidence of type 1 diabetes. Experiences of serious life events have retrospectively been shown to constitute a risk factor for the development of this disease, probably via the biological stress response. Parenting stress and maternal attachment insecurity are other important sources of stress in early childhood.

    Psychological stress increases the need for insulin and may induce insulin resistance, which might add extra pressure on the insulin-producing beta cells in the pancreas (beta-cell stress).

    The aim of the current thesis was to propose and start investigating a stress hypothesis – namely that psychological stress may induce insulin resistance leading to beta-cell stress, which could trigger an autoimmune reaction towards beta-cells in genetically predisposed children. When all the beta cells have been destroyed, insulin can no longer be produced in the body and type 1 diabetes becomes manifest.

    Methods: Families from the prospective population-based ABIS-project, which follows approximately 17 000 children, participated in the empirical studies of the current thesis. The mothers completed questionnaires, including various measures of psychological stress (e.g. parenting stress and experiences of serious life events) and socio-demographic background, at the birth of the child and when the child was 1 as well as 2.5 years of age. Maternal attachment insecurity was assessed with the Adult Attachment Interview. Blood samples drawn from the children at 1 and 2.5 years of age were analyzed for type 1 diabetes-related autoantibodies towards Tyrosine phosphatase (IA-2) and Glutamic Acid Decarboxylase (GAD).

    Findings and Conclusions: Parenting stress and experiences of serious life events like divorce and maternal exposure to violence were associated with the induction of diabetes-related autoimmunity in early childhood, possibly via insulin resistance and beta-cell stress. The risk of developing diabetesrelated autoimmunity after parental divorce or mothers’ exposure to violence was about threefold. None of the results were explained by any of the potential confounding factors analyzed. These results support and strengthen the stress hypothesis, which warrants further investigation.

    Mothers’ attachment insecurity was not associated with the induction of diabetes-related autoimmunity in their infants. However, this lack of association was perhaps due to methodological constraints.

    The vast majority of the parents were calmed or unaffected concerning their participation in the ABIS-project, suggesting that large-scale medical screening-projects in the general population are not in themselves a cause for worry and can be performed without causing increased anxiety.

  • 66.
    Slinde, Frode
    University of Skövde, School of Life Sciences.
    Vad behöver du för information för att göra ett bra arbete som dietist2007In: Dietistaktuellt, ISSN 1102-9285, Vol. 18, no 5, 28-28 p.Article in journal (Other (popular science, discussion, etc.))
  • 67. Srithunyarat, Thanikul
    et al.
    Hagman, Ragnvi
    Höglund, Odd V
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Olsson, Ulf
    Hanson, Jeanette
    Nonthakotr, Chalermkwan
    Lagerstedt, Anne-Sofie
    Pettersson, Ann
    Catestatin, vasostatin, cortisol, and pain assessments in dogs suffering from traumatic bone fractures.2017In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 10, no 1, 129Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Traumatic bone fractures cause moderate to severe pain, which needs to be minimized for optimal recovery and animal welfare, illustrating the need for reliable objective pain biomarkers for use in a clinical setting. The objectives of this study were to investigate catestatin (CST) and vasostatin (VS) concentrations as two new potential biomarkers, and cortisol concentrations, scores of the short form of the Glasgow composite measure pain scale (CMPS-SF), and visual analog scale (VAS) in dogs suffering from traumatic bone fractures before and after morphine administration in comparison with healthy dogs.

    METHODS: Fourteen dogs with hind limb or pelvic fractures and thirty healthy dogs were included. Dogs with fractures were divided into four groups according to analgesia received before participation. Physical examination, CMPS-SF, pain and stress behavior VAS scores were recorded in all dogs. Saliva and blood were collected once in healthy dogs and in dogs with fractures before and 35-70 min after morphine administration. Blood samples were analyzed for CST, VS, and cortisol. Saliva volumes, however, were insufficient for analysis.

    RESULTS: Catestatin and cortisol concentrations, and CMPS-SF, and VAS scores differed significantly between dogs with fractures prior to morphine administration and healthy dogs. After morphine administration, dogs with fractures had significantly decreased CMPS-SF and VAS scores and, compared to healthy dogs, CST concentrations, CMPS-SF, and VAS scores still differed significantly. However, CST concentrations remained largely within the normal range. Absolute delta values for CST significantly correlated with delta values for CMPS-SF. Catestatin and cortisol did not differ significantly before and after morphine administration. Vasostatin concentrations did not differ significantly between groups.

    CONCLUSIONS: Catestatin and cortisol concentrations, CMPS-SF, and VAS scores differed significantly in the dogs with traumatic bone fractures compared to the healthy dogs. Morphine treatment partially relieved pain and stress according to the subjective but not according to the objective assessments performed. However, because of the large degree of overlap with normal values, our results suggest that plasma CST concentrations have a limited potential as a clinically useful biomarker for pain-induced stress.

  • 68. Srithunyarat, Thanikul
    et al.
    Höglund, Odd V
    Hagman, Ragnvi
    Olsson, Ulf
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Lagerstedt, Anne-Sofie
    Pettersson, Ann
    Catestatin, vasostatin, cortisol, temperature, heart rate, respiratory rate, scores of the short form of the Glasgow composite measure pain scale and visual analog scale for stress and pain behavior in dogs before and after ovariohysterectomy.2016In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 9, 381Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The stress reaction induced by surgery and associated pain may be detrimental for patient recovery and should be minimized. The neuropeptide chromogranin A (CGA) has shown promise as a sensitive biomarker for stress in humans. Little is known about CGA and its derived peptides, catestatin (CST) and vasostatin (VS), in dogs undergoing surgery. The objectives of this study were to investigate and compare concentrations of CGA epitopes CST and VS, cortisol, body temperature, heart rate, respiratory rate, scores of the short form of the Glasgow composite measure pain scale (CMPS-SF) and visual analog scales (VAS) for stress and pain behavior in dogs before and after ovariohysterectomy.

    METHODS: Thirty healthy privately owned female dogs admitted for elective ovariohysterectomy were included. Physical examination, CMPS-SF, pain behavior VAS, and stress behavior VAS were recorded and saliva and blood samples were collected before surgery, 3 h after extubation, and once at recall 7-15 days after surgery. Dogs were premedicated with morphine and received carprofen as analgesia for 7 days during the postoperative period.

    RESULTS: At 3 h after extubation, CMPS-SF and pain behavior VAS scores had increased (p < 0.0001) and stress behavior VAS scores, temperature, respiratory rate (p < 0.0001), plasma CST concentrations (p = 0.002) had decreased significantly compared to before surgery. No significant differences were observed in the subjective and physiological parameters between before surgery and at recall, but plasma CST (p = 0.04) and serum cortisol (p = 0.009) were significantly lower at recall. Plasma VS, saliva CST, and heart rate did not differ significantly at any observed time.

    CONCLUSION: Study parameters for evaluating surgery-induced stress and pain changed in dogs subjected to ovariohysterectomy. To further evaluate CST and VS usefulness as pain biomarkers, studies on dogs in acute painful situations are warranted.

  • 69.
    Stahel, Anette
    University of Skövde, School of Life Sciences.
    1,25(OH)2D3 Initially Reduces TGFβ Activity in PC-3 Prostate Cancer Cells2008Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The vitamin D metabolite 1,25(OH)2D3 has long been known to inhibit growth of prostate cancer cells and this mainly through a VDR-mediated pathway controlling target gene expression, resulting in cell cycle arrest, apoptosis and differentiation. Another major way in which 1,25(OH)2D3 inhibits cell growth in prostate cancer is via membrane-initiated steroid signalling, which triggers activation of signal cascades upon steroid binding to a receptor complex, leading to induction of genes regulating cell growth, proliferation and apoptosis. The main prostate cancer inhibiting membrane-initiated route is the TGFβ signalling pathway, elicited by the protein TGFβ. In this experiment the activating effects of 1,25(OH)2D3 on TGFβ in prostate cancer cells, as well as two other important proteins downstream in this cascade, Smad2 and 3, were investigated. PC-3 cells were incubated for 3, 5, 10, 30 and 60 minutes as well as 38 hours both together with 1,25(OH)2D3 of the concentrations 10-10 and 10-7 M and without. As the downstream cascade protein JNK is a known activator of Smad2/3, this procedure was also repeated with a JNK inhibitor. An ELISA assay scanning for activated TGFβ was then performed on supernatants from the cells treated without JNK inhibitor. In addition, a Western Blot scanning for activated Smad2 and 3 was performed on supernatants from all groups of treatment. The analysis of the result values showed that 10-10 M 1,25(OH)2D3 significantly lowered the content of active TGFβ in PC-3 cells within 3 and 5 minutes. Unfortunately the Western Blot was unsuccessful and needs therefore be repeated.

  • 70.
    Stahel, Anette
    University of Skövde, School of Life Sciences.
    24,25(OH)2D3 and Regulation of Catalase Activity in LNCaP Prostate Cancer Cells: A Study of Long-term Effects2008Student thesis
    Abstract [en]

    The vitamin D metabolite 1,25(OH)2D3 has long been known to inhibit growth of prostate cancer cells and this has been attributed to a VDR-mediated pathway controlling target gene expression, resulting in cell cycle arrest, apoptosis and differentiation. New research has shown that another vitamin D metabolite, 24,25(OH)2D3, inhibits proliferation of prostate cancer cells as well, more specifically, cells of the line LNCaP. It is not clear exactly how 24,25(OH)2D3 exerts this cancer growth inhibition but it has been shown that it is to some extent regulated via G protein coupled signalling pathways. Catalase is a haem-containing redox enzyme found in the majority of animal cells, plant cells and aerobic microorganisms. This enzyme is very important because it prevents excessive accumulation of the strongly oxidizing agent H2O2 which otherwise can do damage to the cells. Because of this preventive effect of catalase, important cellular processes which generate H2O2 as by-product can proceed safely. Biochemical analysis of catalase has shown that it binds endogenously to 24,25(OH)2D3. The fact that 24,25(OH)2D3 has anti-proliferative effects on prostate cancer cells combined with the fact that it binds to catalase generates the hypothesis that this binding interferes with the essential task of catalase to keep the cell free from accumulation of destructive H2O2, and by means of this interference induces apoptosis. Finding out about the cancer growth inhibiting mechanism behind each vitamin D metabolite is important and may be a lead in the search for a new, better treatment of prostate cancer. This is a follow-up to an earlier study, and the specific aim of this project was to find out if and in what way 24,25(OH)2D3 affects the enzymatic activity of catalase in LNCaP cells during long-term treatment (up to 48 hours). In this experiment LNCaP cells were incubated for 48 hours together with 24,25(OH)2D3 of the concentration 10-8 M, then a catalase assay was performed on the cells including fluorescence-mediated measuring of catalase activity in both treated and untreated cells. The analysis of the result values showed that despite of the rather high dose used, 24,25(OH)2D3 has no statistically significant effect on catalase activity in cells of the line LNCaP, regardless of time.

  • 71.
    Stillfors, Caroline
    Örebro University, School of Health and Medical Sciences.
    Ultraljudsscreening av bukaortaaneurysm: precision och reproducerbarhet2008Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Abdominellt aortaaneurysm (AAA) är en sjukdom som främst drabbar äldre män. Sjukdomen är förknippat med en mycket hög dödlighet. Det är viktigt att patienterna fångas upp under den latenta delen av sjukdomsförloppet (före ruptur), och erbjuds behandling. En hälsoundersökning (screening) av patienter i riskzonen skulle kunna sänka den AAA-relaterade mortaliteten. För denna typ av screening används ultraljud. Ofta är det läkare som utför undersökningarna men med dagens läkarbrist behöver man tänka om. Denna litteraturstudie undersöker om screening för AAA kan sänka mortaliteten i sjukdomen, men också precisionen och reproducerbarheten hos ultraljud som undersökningsmetod och om annan vårdpersonal kan utföra screeningen. Resultaten visar på ultraljudets höga precision och reproducerbarhet. Användarvänligheten gör att annan vårdpersonal efter adekvat utbildning med fördel kan utföra undersökningen. Screening för AAA sänker dramatiskt dödligheten i sjukdomen. Ytterligare forskning behövs kring screening för AAA hos andra riskgrupper, samt kring de patofysiologiska orsakerna bakom utveckling, expansion och ruptur.

  • 72.
    Strand, Magnus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Estrogen signaling in stroke: genetic and experimental studies2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Stroke is a common and multifactorial disease influenced by genetic and environmental risk factors. It is a highly heterogeneous entity consisting of two main types, ischemic (80%) and hemorrhagic (20%) stroke. The most common form of hemorrhagic stroke is intracerebral hemorrhage (ICH). Ischemic stroke mainly results from thrombotic or embolic events, while ICH is caused by the rupture of an artery in the brain.

    The mean age of first-ever stroke is 75 years (73 vs. 78 years, for men and women, respectively) and the age-specific stroke incidence is higher for men as compared to women, suggesting that hormonal factors confer protection. A large body of experimental and observational studies shows that estrogens exert beneficial effects in the cardiovascular system. However, large, recent, clinical randomized trials have failed to demonstrate a lower risk of stroke with hormone replacement therapy (HRT) in elderly postmenopausal women. It is possible that HRT may only protect a subgroup of women. Here, genetic predisposition might be involved. Stroke incidence is 50% higher in northern compared to southern Sweden, suggesting a genetic predisposition in this population. This relatively homogeneous population displays founder effects, making it well suited for genetic studies. Since 1985, the MONICA and VIP projects have conducted large-scale cardiovascular health surveys in this population. Information about conventional stroke risk determinants and also DNA have been collected, and two prospective, nested case-referent cohorts (113 cases and 226 controls; 275 cases and 549 controls) have been sampled.

    To investigate whether genes of the estrogen signaling system may be important in stroke development, we performed genetic association studies, including specific functional single nucleotide polymorphisms in the genes for estrogen receptor alpha (ERα, ESR1), and its target genes osteoprotegerin (OPG, TNFRS11B) and interleukin-6 (IL-6, IL6). We found a significant association between the common c.454-397T/T genotype in ESR1 and ICH, remaining after adjustments for conventional stroke risk factors. The c.454-397T/T genotype also associated with increased systolic (SBP) and diastolic blood pressure (DBP). The combination of c.454- 397T/T and either hypertension, increased SBP, or increased DBP boosted this association substantially and significant synergistic effects on ICH risk between this genotype and increased blood pressure were demonstrated. In a second study, we found a similar association between the common OPG-1181C/C genotype and ICH.

    Cognitive impairments, including spatial memory and learning deficiencies, are common after stroke. Estrogens improve cognitive functions, including memory and learning processes, in postmenopausal women and ovariectomized rodents. Post-ischemic housing of rats in an enriched environment (EE) improves recovery of spatial memory and learning impairments. Both estrogen and EE induce neuroplasticity in the hippocampus. We hypothesized that 17β- estradiol combined with EE would accelerate recovery after experimental focal brain ischemia in ovariectomized rats and that such improvements could be related to expression of nerve growth factor-induced gene A (NGFI-A) in the hippocampus. Five to six weeks after middle cerebral artery occlusion, 17β-estradiol–treated rats housed in an EE showed significant improvements in cognitive function (i.e., shorter latency and path in the Morris water maze task) and significantly higher NGFI-A mRNA expression in bilateral cornu ammonis 1 (CA1) and ipsilateral dentate gyrus (DG) compared to placebo-treated animals in EE.

    In conclusion, we present evidence for the association between polymorphic variants in the ESR1 and TNFRS11B genes and ICH and show that 17β-estradiol in combination with EE accelerates cognitive functions in a rat stroke model, putatively through upregulation of NGFI-A in hippocampal subregions. These findings may contribute to an increased understanding of the underlying genetic etiology of ICH and may be informative for the primary prevention of this disease. They also provide hope for 17β-estradiol combined with early environmental enrichment as a novel therapeutic option following ischemic stroke.

  • 73.
    Stridsberg, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Pettersson, Ann
    Hagman, Ragnvi
    Westin, Christoffer
    Höglund, Odd
    Chromogranins can be measured in samples from cats and dogs2014In: BMC Research Notes, ISSN 1756-0500, Vol. 7, 336Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Methods for objective evaluation of stress in animals are important, but clinically difficult. An alternative method to study the sympathetic activity may be to investigate Chromogranin A (CGA), Chromogranin B (CGB) and Secretogranin II (SG2). The aim of this study was to investigate the cross-reactivity of CGA, CGB and SG2 between man, cat and dog and to explore possibilities to measure these proteins in samples from cats and dogs.

    RESULTS: Adrenal gland extracts from feline and canine species were measured by region-specific radioimmunoassays in different dilution steps to explore possible inter species cross reactivity. High cross reactivity was found for cats in the CGA17-38, CGA324-337, CGA361-372, CGB and SG2 assays. High cross reactivity was found for dogs in the CGA17-38, CGA361-372, CGB and SN assays. The method measuring the intact CGA was not useful for measurements in cats and dogs.

    CONCLUSIONS: Region-specific assays measuring defined parts of CGA, CGB and SG2 can be used for measurements in samples from cats and dogs. These results are promising and will allow for further studies of these proteins as possible clinical biomarkers in cats and dogs.

  • 74.
    Ström, Jakob O.
    et al.
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Ingberg, Edvin
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Druvefors, Emma
    Ryhov County Hospital, County Council of Jönköping, Jönköping, Sweden.
    Theodorsson, Annette
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    The female menstrual cycle does not influence testosterone concentrations in male partners2012In: Journal of Negative Results in Biomedicine, ISSN 1477-5751, E-ISSN 1477-5751, Vol. 11, 1-7 p., 1Article in journal (Refereed)
    Abstract [en]

    Background: The time of ovulation has since long been believed to be concealed to male heterosexual partners. Recent studies have, however, called for revision of this notion. For example, male testosterone concentrations have been shown to increase in response to olfactory ovulation cues, which could be biologically relevant by increasing sexual drive and aggressiveness. However, this phenomenon has not previously been investigated in real-life human settings. We therefore thought it of interest to test the hypothesis that males' salivary testosterone concentrations are influenced by phases of their female partners' menstrual cycle; expecting a testosterone peak at ovulation.

    Methods: Thirty young, healthy, heterosexual couples were recruited. During the course of 30-40 days, the women registered menses and ovulation, while the men registered sexual activity, physical exercise, alcohol intake and illness (confounders), and obtained daily saliva samples for testosterone measurements. All data, including the registered confounders, were subjected to multiple regression analysis.

    Results: In contrast to the hypothesis, the ovulation did not affect the testosterone levels, and the resulting testosterone profile during the menstrual cycle was on the average flat. The specific main hypothesis, that male testosterone levels on the day of ovulation would be higher than day 4 of the cycle, was clearly contradicted by a type II error(β)-analysis (< 14.3% difference in normalized testosterone concentration; β = 0.05).

    Conclusions: Even though an ovulation-related salivary testosterone peak was observed in individual cases, no significant effect was found on a group level.

  • 75.
    Ström, Jakob O.
    et al.
    Linköping University Hospital, Linköping, Sweden.
    Theodorsson, Annette
    Linköping University Hospital, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University Hospital, Linköping, Sweden.
    Substantial discrepancies in 17beta-oestradiol concentrations obtained with three different commercial direct radioimmunoassay kits in rat sera2008In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 68, no 8, 806-813 p.Article in journal (Refereed)
    Abstract [en]

    The extensive use of oestrogen for contraception and amelioration of post-menopausal symptoms has made it the subject of substantial recent research efforts, and ovariectomized (ovx) rats treated with exogenous ovarial hormones are important when investigating the effects and mechanisms of oestrogen actions. The crucial need to control and monitor plasma levels of 17beta-oestradiol calls for accurate, precise and robust assay methods. The performance of direct radioimmunoassays (RIAs) in measurement of 17beta-oestradiol has been reported previously for human samples, but to our knowledge not for rat samples. In the current study, 552 serum samples from ovx, native and hormone-treated rats were used to compare the performance of three commercially manufactured direct RIAs from the companies DPC (Siemens Healthcare Diagnostics Inc., formerly Diagnostic Products Corporation), DSL (Diagnostic Systems Labs) and MPB (MP Biomedicals, formerly ICN Biomedicals). Substantial differences in results between the three assay methods were found when measuring serum 17beta-oestradiol concentrations. The following formulas describing the relation between the different methods were obtained using weighted Deming's orthogonal regression (based on pg/mL): DSL = 0.43*DPC+12.3, MPB = 2.1*DPC+84.7 and DSL = 4.8*MPB+22.2. Furthermore, a preceding diethyl ether extraction step of the serum appears to impair the performance of the RIAs in the present samples (based on pg/mL): DPC(ex) = 0.39*DPC(unex)+0.76, DSL(ex) = 0.32*DSL(unex)-1.7 and MPB(ex) = 0.22*MPB(unex)+1.4.

  • 76.
    Strömberg, Jessica
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Sex and stress steroid modulation of GABA mediated chloride ion flux in rat CNS2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Sex and stress steroids are metabolized to 3a-hydroxy-pregnane-steroid metabolites such as allopregnanolone (Allo) and tetrahydrodeoxycorticosterone (THDOC). Allo and THDOC are neuroactive steroids that are metabolized in the brain and act in brain as potent positive GABAA receptor function modulators. Allo as well as THDOC levels increase during stress. Allo has been associated with a number of symptoms and malfunctions such as impaired memory function and negative mood symptoms in a subgroup of individuals both for animals and humans. Pregnane steroids with 3b-hydroxy-configuration (3b-steroids) have been shown to reduce the Allo enhanced GABA effect.

    Aims: The aims for the present thesis were to investigate the effect of 3b-steroids on the GABA mediated GABAA receptor function in presence of positive GABAA receptor modulators. Further, the regional variances between the 3b-steroids as well as the mechanism of the effect were studied. Finally, the effect of stress steroid metabolites on the GABAA receptor function was investigated.

    Results: 3b-OH-5a-pregnane-20-one reduced the Allo enhanced GABA mediated chloride ion uptake into cortical microsacs. The 3b-isomer reduced the efficacy of Allo without shift the concentration response curve. It is therefore suggested that the 3b-isomer has a non-competitive effect. Further, it was shown that the 3b-isomer reduced the Allo effect in a selective way since the 3b-isomer did not interact with other positive modulators or with GABA itself. Five tested 3b-steroids reduced the Allo enhanced GABA mediated chloride ion uptake in cerebral cortex and hippocampus as well as the Allo prolongation on spontaneous inhibitory postsynaptic currents (sIPSCs) in preoptic nucleus. In cerebellum on the other hand the 3b-steroids showed to have weaker or no effect compared to the other tested regions. Interestingly, in absence of Allo, two of the 3b-steroids positively modulated the GABA stimulated GABAA receptor function. In absence of Allo, 5b-pregnane-3b,20(R)-diol increased the desensitization rate of current response. In contrast to the reducing effect on the Allo induced prolongation on sIPSCs, the effect of the 3b-steroid on GABA application, was not altered in presence of Allo. The mechanism of the 3b-steroid is therefore suggested being desensitization dependent in contrast to Allo, which has been suggested to decrease the GABA unbinding rate. In contrast to the enhanced effect of Allo, glucocorticoid metabolites reduced the GABA mediated chloride ion uptake in a concentration dependent way. The results in present thesis indicate that both sex and stress steroid metabolites interact with the GABAA receptor function. The knowledge that diversity of endogenous steroids interact with the GABAA receptor function is of importance for further understanding of different sex and stress steroid related symptoms and syndromes.

  • 77.
    Suarez Sipmann, Fernando
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Titrating Open Lung PEEP in Acute Lung Injury: A clinical method based on changes in dynamic compliance2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The recognition that supportive mechanical ventilation can also damage the lung, the so called ventilation induced lung injury (VILI), has revived the more than 40 year long debate on the optimal level of PEEP to be used. It is established that the prevention of VILI improves patient outcome and that PEEP exerts protective effects by preventing unstable diseased alveoli from collapsing. Therefore, the term “open lung PEEP” (OL-PEEP) has been introduced as the end-expiratory pressure that keeps the lung open after its collapse has been eliminated by an active lung recruitment manoeuvre. The determination of such an optimal level of PEEP under clinical circumstances is difficult and remains to be investigated.

    The aim of this study was to investigate the usefulness of breath by breath monitoring of dynamic compliance (Cdyn) as a clinical means to identify OL-PEEP at the bedside and to demonstrate the improvement in lung function resulting from its application.

    In a porcine lung lavage model of acute lung injury PEEP at maximum Cdyn during a decremental PEEP trial after full lung recruitment was related to the onset of lung collapse and OL-PEEP could be found 2 cmH2O above this level Ventilation at OL-PEEP was associated with improved gas exchange, efficiency of ventilation, lung mechanics and less than 5% collapse on CT scans. In addition, dead space, especially its portion related to alveolar gas changed characteristically during recruitment, PEEP titration and collapse thereby helping to identify OL-PEEP.

    The beneficial effects of OL-PEEP on lung function and mechanics was demonstrated in a porcine model of VILI. OL-PEEP improved lung function and mechanics when compared to lower or higher levels prior to or after lung recruitment. By using electrical impedance tomography it could be shown that PEEPs within the range of 14 to 22 cmH2O resulted in a similar redistribution of both ventilation and perfusion to the dorsal regions of the lung. OL-PEEP resulted in the best regional and global matching of ventilation and perfusion explaining the drastic improvements in gas exchange. Also regional compliance was greatly improved in the lower half of the lung as compared to all other situations.

    In ARDS patients OL-PEEP could be identified applying the same protocol. The physiological changes described could now be reproduced and maintained during a four hours study ventilation period in real patients at four study centres.

    In conclusion, the usefulness of dynamic compliance for identifying open lung PEEP during a decremental PEEP trial was demonstrated under experimental and clinical conditions. This PEEP should then be used as an essential part of any lung protective ventilation strategy. The impact of ventilating ARDS patients according to the principles described in these studies on outcome are currently being evaluated in an international randomized controlled trial.

  • 78.
    Sundh, Josefin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Respiratory Medicine.
    Ställberg, Björn
    Department of Public Health and Caring Science, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
    Lisspers, Karin
    Department of Public Health and Caring Science, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
    Kämpe, Mary
    Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden.
    Janson, Christer
    Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Epidemiology and Biostatistics; Research Department of Epidemiology and Public Health, University College, London, United Kingdom.
    Comparison of the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ) in a Clinical Population2016In: COPD: Journal of Chronic Obstructive Pulmonary Disease, ISSN 1541-2555, E-ISSN 1541-2563, Vol. 13, no 1, 57-65 p.Article in journal (Refereed)
    Abstract [en]

    Introduction: The COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ) are both clinically useful health status instruments. The main objective was to compare CAT and CCQ measurement instruments.

    Methods: CAT and CCQ forms were completed by 432 randomly selected primary and secondary care patients with a COPD diagnosis. Correlation and linear regression analyses of CAT and CCQ were performed. Standardised scores were created for the CAT and CCQ scores, and separate multiple linear regression analyses for CAT and CCQ examined associations with sex, age (≤ 60, 61-70 and >70 years), exacerbations (≥1 vs 0 in the previous year), body mass index (BMI), heart disease, anxiety/depression and lung function (subgroup with n = 246).

    Results: CAT and CCQ correlated well (r = 0.88, p < 0.0001), as did CAT ≥ 10 and CCQ ≥ 1 (r = 0.78, p < 0.0001). CCQ 1.0 corresponded to CAT 9.93 and CAT 10 to CCQ 1.29. Both instruments were associated with BMI < 20 (standardised adjusted regression coefficient (95%CI) for CAT 0.56 (0.18 to 0.93) and CCQ 0.56 (0.20 to 0.92)), exacerbations (CAT 0.77 (0.58 to 0.95) and CCQ 0.94 (0.76 to 1.12)), heart disease (CAT 0.38 (0.17 to 0.59) and CCQ 0.23 (0.03 to 0.43)), anxiety/depression (CAT 0.35 (0.15 to 0.56) and CCQ 0.41 (0.21 to 0.60)) and COPD stage (CAT 0.19 (0.05 to 0.34) and CCQ 0.22 (0.07 to 0.36)).

    Conclusions: CAT and CCQ correlate well with each other. Heart disease, anxiety/depression, underweight, exacerbations, and low lung function are associated with worse health status assessed by both instruments.

  • 79.
    Sundström, Gunnel
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Hyaluronan in normal and malignant bone marrow: a clinical and morphological study with emphasis on myelofibrosis2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Fibrosis in the bone marrow is usually denominated myelofibrosis and may contribute to impaired hematopoiesis. Myelofibrosis is seen both in malignant and non-malignant diseases.

    The normal microenvironment in the bone marrow consists of a heterogenous population of hematopoietic and non-hematopoietic stromal cells, their extracellular products and hematopoietic cytokines. The stromal cells produce a complex array of molecules, among others collagens and glycosaminoglycans (GAGs) of which hyaluronan (HYA) is the most abundant. Marrow fibrosis results from an increased deposition of collagens, which are polypeptides. Staining for reticulin, mostly composed of collagen type III, is the common way of visualizing myelofibrosis. HYA, like the collagens, is widely distributed in connective tissues. Little is known about the distribution of HYA in bone marrow.

    The aims of this thesis have been to determine how HYA is distributed in normal and malignant bone marrow, compared to reticulin staining, and to follow patients with chronic myeloproliferative diseases (CMPD) during two years treatment with anagrelide considering development of cellularity and fibrosis.

    In bone marrow biopsies from healthy volunteers, the controls, HYA was found in a pattern that was concordant with the reticulin staining.

    Comparing patients with different malignant diseases with and without bone marrow involvemen, HYA staining was found to be significantly stronger in both groups compared to the controls.

    The HYA scores were also significantly higher in the bone marrow of patients with de novo acute myeloid leukemia (AML), compared to the controls.

    There was a correlation between HYA and reticulin in the patients with de novo AML, and in the patients with different malignant diseases with and without bone marrow involvement as in the controls.

    Increase of HYA, reticulin and cellularity in the bone marrow of patients with CMPD after two years of treatment with anagrelide indicated progression of fibrosis. Anagrelide is a valuable drug for reduction of platelets but seems unable to stop progression of fibrosis and hypercellularity.

    HYA is an interesting molecule with properties not only contributing to the structure of extracellular matrix but also to cell signaling and behaviour, although the understanding of the detailed mechanisms is still incomplete.

  • 80.
    Svantesson, Mia
    Örebro University, School of Health and Medical Sciences.
    Postpone death?: Nurse-physician perspectives on life-sustaining treatment and ethics rounds2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The starting point of the present thesis is nurses’ reported experiences of disagreements with physicians for pushing life sustaining treatment too far. The overall aim was to describe and compare nurses’ and physicians’ perspectives on the boundaries for life-sustaining treatment and to evaluate whether ethics rounds could promote mutual understanding and stimulate ethical reflection. A mixed methods design with qualitative and quantitative data was used, including interviews and questionnaires. The health professionals’ experiences/perceptions were based on known patients foremost from general wards, but also intensive care units, at four Swedish hospitals. The first two studies treated the perspective on boundaries for life-sustaining treatment and the last two evaluated philosopher- ethicist led ethics rounds. Analysis of data was performed using a phenomenological approach and content analysis as well as comparative and descriptive non-parametric statistics.

    In the first study, the essence of the physicians’ decision-making process to limit life-sustaining treatment for ICU patients, was a process of principally medical considerations in discussions with other physicians. In the second study, there were more similarities than differences between nurses’ and physicians’ opinions regarding the 714 patients studied. The physicians considered limited treatment as often as the nurses did. The ethics rounds studies generated mixed experiences/perceptions. It seemed that more progress was made toward the goal of promoting mutual understanding than toward the goal of stimulating ethical reflection. Above all, the rounds seemed to meet the need for a forum for crossing over professional boundaries. The most salient finding was the insight to enhance team collaboration, that the interprofessional dialogue was sure to continue. Predominating new insights after rounds were interpreted as corresponding to a hermeneutic approach. One of nurses’ negative experiences of the ethics rounds was associated with the lack of solutions. Based on the present findings, one suggestion for improvement of the model of ethics rounds is made with regard to achieving a balance between ethical analyses, conflict resolution and problem solving. In conclusion, the present thesis provides strong evidence that differences in opinions regarding boundaries for life-sustaining treatment are not associated with professional status. The findings support the notion of a collaborative team approach to end-of-life decision-making for patients with diminished decisionmaking capacity. There is an indication that stimulation of ethical reflection in relation to known patients may foremost yield psychosocial insights. This could imply that social conflicts may overshadow ethical analysis or that ethical conflicts and social conflicts are impossible to distinguish.

  • 81.
    Thorfinn, Johan
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Studies on sitting pressure and buttock microcirculation: aiming at developing an alarm in the prevention of pressure ulcers in patients with spinal cord injuries2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Pressure ulcers in patients with spinal cord injuries are a major problem, the prevalence in this group being reported as high as 20 – 30 percent. Most pressure ulcers develop around the pelvic girdle, and the key-contributing factor in the development of pressure ulcers is ischaemia due to longstanding pressure. Loss of mobility and lack of sensation below the level of injury are prominent risk factors for the development of pressure ulcers. Although many factors are known to contribute to pressure ulcer development, the exact aetiology is not completely clear. Prevention is suggested as the best way to deal with the problem. The studies in this thesis investigate some aspects of the physiology of sitting in patients with spinal cord injuries and healthy controls, aiming at developing a pressure ulcer alarm device to aid in the prevention of pressure ulcers. Methods used are laser Doppler perfusion imaging (LDPI) for measurement of superficial skin blood flow, as well microdialysis and a microelectrode (Licox®) to measure direct and indirect signs of ischaemia. In addition sitting pressures are mapped. The main findings are that patients with spinal cord injuries have almost four-fold mean maximum sitting pressures 43 and 49 N/cm2, left and right buttock) compared with healthy controls 12 and 13 N/cm2, left and right buttock). In the subcutaneous fat in healthy individuals, the tissue oxygen pressure decreases significantly during 30 minutes of sitting on a wheel chair cushion 13,7 mmHg) compared with 30 minutes of sitting on a hard surface 19,8 mmHg) implying that the tissues deep in the skin are exposed to a reduction in blood supply. This is also confirmed by a decrease in extracellular glucose during sitting for 30 minutes on a hard surface 1,8 mmol/L) and on a wheel chair cushion 1,7 mmol/L). The post-sitting reactive hyperaemia is dependent on duration of sitting in both patients and healthy subjects. It seems to be attenuated in patients in the sitting position but intensified while lying prone. Furthermore, four repeated loadings on a hard surface 15 minutes of sitting followed by five minutes of rest) without allowing the tissues to return to resting perfusion results in a significantly increasing reactive hyperaemia for each loading in healthy subjects, suggesting that it is important to unload the buttock skin completely before the next sitting period starts. This thesis also describes the construction of an alarm device that measures surface interface pressures during sitting continuously in eight predefined points, to alert the user by an audible signal after a given period of time when the pressure has reached a dangerously high level. It is concluded that the reactive hyperaemia that is observed in the buttock skin after sitting, as well as the reduction in glucose and oxygen in adipose tissue during sitting, are due to a reduction in blood supply relative or absolute ischaemia) caused by a compression of the vasculature by the ischial tuberosities. These findings imply a multilayer aetiology in pressure ulcer development. The altered hyperaemic reaction in patients with spinal cord injuries after sitting is possibly related to alterations in sympathetic activity due to the cord lesion. Lastly, the alarm device is supposed to be an aid to pressure ulcer prevention in patients with spinal cord injuries who lack normal sensory feedback.

  • 82.
    Toss, Henrik
    et al.
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Lönnqvist, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, David
    Acreo Swedish ICT AB, Norrköping, Sweden.
    Sawatdee, Anurak
    Acreo Swedish ICT AB, Norrköping, Sweden.
    Nissa, Josefin
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Fabiano, Simone
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Berggren, Magnus
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Kratz, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Science & Engineering. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Simon, Daniel T
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Ferroelectric Surfaces for Cell Release2017In: Synthetic metals, ISSN 0379-6779, E-ISSN 1879-3290, Vol. 228, 99-104 p.Article in journal (Refereed)
    Abstract [en]

    Adherent cells cultured in vitro must usually, at some point, be detached from the culture substrate. Presently, the most common method of achieving detachment is through enzymatic treatment which breaks the adhesion points of the cells to the surface. This comes with the drawback of deteriorating the function and viability of the cells. Other methods that have previously been proposed include detachment of the cell substrate itself, which risks contaminating the cell sample, and changing the surface energy of the substrate through thermal changes, which yields low spatial resolution and risks damaging the cells if they are sensitive to temperature changes. Here cell culture substrates, based on thin films of the ferroelectric polyvinylidene fluoride trifluoroethylene (PVDF-TrFE) co-polymer, are developed for electroactive control of cell adhesion and enzyme-free detachment of cells. Fibroblasts cultured on the substrates are detached through changing the direction of polarization of the ferroelectric substrate. The method does not affect subsequent adhesion and viability of reseeded cells.

    The full text will be freely available from 2019-04-25 14:36
  • 83.
    Türkmen, Sahruh
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Löfgren, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Birzniece, Vita
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Johansson, Inga-Maj
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Tolerance development to Morris water maze test impairments induced by acute allopregnanolone2006In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 139, no 2, 651-659 p.Article in journal (Refereed)
    Abstract [en]

    The progesterone metabolite allopregnanolone, like benzodiazepines, reduces learning and impairs memory in rats. Both substances act as GABA agonists at the GABA-A receptor and impair the performance in the Morris water maze test. Women are during the menstrual cycle, pregnancy, and during hormone replacement therapy exposed to allopregnanolone or allopregnanolone-like substances for extended periods. Long-term benzodiazepine treatment can cause tolerance against benzodiazepine-induced learning impairments. In this study we evaluated whether a corresponding allopregnanolone tolerance develops in rats. Adult male Wistar rats were pretreated for 3 days with i.v. allopregnanolone injections (2 mg/kg) one or two times a day, or for 7 days with allopregnanolone injections 20 mg/kg intraperitoneally, twice a day. Thereafter the rats were tested in the Morris water maze for 5 days and compared with relevant controls. Rats pretreated with allopregnanolone twice a day had decreased escape latency, path length and thigmotaxis compared with the acute allopregnanolone group that was pretreated with vehicle. Pretreatment for 7 days resulted in learning of the platform position. However, the memory of the platform position was in these tolerant rats not as strong as in controls only given vehicle. Allopregnanolone treatment was therefore seen to induce a partial tolerance against acute allopregnanolone effects in the Morris water maze.

  • 84.
    Van Vliet, Jolanda S
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Rasanen, Leena
    Department of Food and Environmental Sciences, Division of Nutrition, University of Helsinki, Finland..
    Gustafsson, Per A
    Linköping University, Department of Clinical and Experimental Medicine, Child and Adolescent Psychiatry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Nelson, Nina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Overweight perception among adolescent girls in relation to appearance of female characteristics2014In: Paediatrics and Health, ISSN 2052-935X, Vol. 2, no 1, 1-7 p.Article in journal (Refereed)
    Abstract [en]

    Background: Overweight perception has been shown to be important for health related adolescent behavior, particularly in girls. Body perception may be affected by bodily changes, especially changes visible for others. Female pubertal development is characterized by many physical changes, such as accelerated growth and altered body fat distribution. This study examined the role of appearance of female characteristics in the risk for overweight perception among healthy adolescent girls.

    Methods: 220 girls, aged 11–16, provided self-reports on body perception and pubertal maturation before anthropometric measurements of height, weight, hip and waist circumference (WC). Logistic regression modeling was used to study the appearance of pubertal characteristics in relation to body perception.

    Results: Of the 76 girls (35%) perceiving themselves as overweight, only 14 and 36 girls were overweight according to body mass index and waist circumference respectively. Girls reporting breast development and acne (n=144) were more likely to perceive themselves as overweight than girls who did not report this appearance (n=76). These findings persist after adjusting for overweight according to WC. Non-overweight (n=170) rather than overweight girls reporting characteristics (n=50) were at risk of perceiving themselves overweight.

    Conclusions: Girls may confuse natural changes occurring during adolescent development with being overweight. It is therefore important to improve the understanding about the physical changes that normally occur during puberty along with the girls' own perception of these bodily changes among girls themselves, their parents, at schools, and other healthcare services.

  • 85.
    Vánky, Farkas
    Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Surgery for aortic stenosis: with special reference to myocardial metabolism, postoperative heart failure and long-term outcome2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Postoperative heart failure (PHF) remains a major determinant of the outcome after cardiac surgery. However, characteristics of and risk factors for PHF after valve surgery have received little attention.

    Post-ischaemic disturbances of myocardial metabolism that may contribute to PHF and are amenable to metabolic treatment have been identified early after coronary surgery (CABG). Knowledge derived from these studies may not be applicable to other patient groups. We therefore studied myocardial energy metabolism in 20 elective patients undergoing aortic valve replacement (AVR) for isolated aortic stenosis (AS). The metabolic studies indicated that myocardial oxidative metabolism had not fully recovered when the procedure was completed. Free fatty acids were the only major substrates taken up by the heart. Signs of preoperative and postoperative metabolic adaptation with substantial uptake of glutamate, previously demonstrated in patients with coronary artery disease, were found. Postoperative infusion of glutamate, (2 mL/kg body weight and hour of 0.125 M solution) based on assessment of myocardial glutamate requirements in CABG patients, resulted in a two-fold increase in myocardial glutamate uptake and a seven-fold increase in AV differences across the leg. This was associated with a significant myocardial uptake of lactate and metabolic changes in the leg suggesting mitigation of net amino acid loss and peripheral tissue lipolysis.

    Characteristics of and risk factors for PHF were evaluated in 398 patients undergoing isolated AVR for AS from 1 January 1995 to 31 December 2000. These were compared with 398 patients, matched for age and sex, undergoing on-pump isolated CABG. Forty-five AVR and 47 CABG patients fulfilled criteria for PHF and these were studied in detail. PHF usually presented at weaning from cardiopulmonary bypass. After CABG it was closely associated with preoperative ischaemic events and intraoperatively acquired myocardial infarction. Potential causes and eliciting events of PHF after AVR for AS were obvious only in one-third of the patients. Risk factors for PHF after AVR for AS indicated either pre-existing myocardial dysfunction, increased right or left ventricular after-load, or intraoperatively acquired myocardial injury. PHF was associated with high early mortality after CABG, whereas the consequences of PHF after AVR for AS became evident only with time, resulting in a 42% five-year mortality. Although PHF had a different temporal impact on late mortality after CABG and AVR for AS, it emerged as the statistically most significant risk factor for mortality occurring within 5 years from surgery both after AVR for AS and after CABG. Potential implications of our findings include needs for greater focus on preoperative surveillance of patients with AS for optimal timing of surgery, mitigation of intraoperatively acquired myocardial injury and tailoring of treatment for PHF. Furthermore, the findings have implications for long-term follow up of AS patients after surgery.

  • 86. Wahlström, Helene
    et al.
    Carpenter, Tim
    Giesecke, Johan
    Andersson, Mikael
    Stockholm University, Faculty of Science, Department of Mathematics. Matematisk statistik.
    Englund, Lena
    Vågsholm, Ivar
    Herd-based monitoring for tuberculosis in extensive swedish deer herds by culling and meat inspection rather than by intradermal tuberculin testing.2000In: Preventive Veterinary Medicine, ISSN 0167-5877, Vol. 43, no 2, 103-16 p.Article in journal (Refereed)
    Abstract [en]

    The effect of random slaughter and meat inspection as a tool to detect or eradicate tuberculosis in large, extensive deer herds in Sweden was evaluated. A computer spreadsheet model based on the Reed-Frost method was developed. Numbers of new infections and of infected deer slaughtered as well as probability of detecting tuberculosis or slaughtering all infected deer in a herd, were simulated. The model predicted that, given a 20% annual slaughter and that disease was introduced with one infected deer, the infection would be detected or eliminated in most herds (90%) after 15 years.

  • 87.
    Wanby, Pär W.
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    On certain genetic and metabolic risk factors for carotid stenosis and stroke2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The present study evaluated genetic and metabolic factors influencing the risk of acute cerebrovascular disease (CVD) and internal carotid artery stenosis (ICA stenosis) in a Swedish community. The threonine (T) containing protein of the FABP2 A54T gene polymorphism has a greater affinity for long chain fatty acids (FFAs) than the alanine (A) containing protein. This altered affinity for FFAs has been shown to affect the intestinal absorption of fatty acids and consequently the fatty acid composition of serum lipids, in particularly postprandially. Endothelium derived NO is a potent vasodilator and antiatherogenic agent. Asymmetric dimethyl arginine (ADMA) is an endogenous competitive inhibitor of endothelial nitric oxide synthase (eNOS). ADMA has been shown to be involved in the pathogenesis of atherosclerotic disease, and ADMA inhibits eNOS by displacement of L-arginine from the enzyme, which in turn is believed to affect the amount of NO available within the endothelium.

    The FABP2 A54T gene polymorphism was analyzed in 407 patients with acute CVD and also in a subset of these patients whose carotids had been evaluated with ultrasound. Both the FABP2 polymorphism and a common polymorphism of the eNOS gene, Glu298Asp, were analyzed in a different population consisting of 54 matched pairs of patients with ICA stenosis and controls. ADMA levels were measured in both study populations.

    We found that the T54 allele was more frequent in patients with transient ischaemic attacks (TIA), and that the TT genotype was more prevalent in young, non-smoking patients with CVD than in controls.

    Increased concentrations of ADMA were observed in cardio-embolic infarction and TIA, but not significantly in non-cardio-embolic infarction nor in haemorrhagic stroke. In multivariate logistic regression models, CVD increased across quartiles of ADMA in all subgroups, but this association was only significant in the TIA group. A decreased arginine/ADMA ratio, a measure of NO availability was associated with CVD in the entire study population. Patients with severe carotid stenosis had significantly higher ADMA levels than the controls. Allele and genotype frequencies of the FABP2 and eNOS polymorphisms did not differ between patients with ICA stenosis and controls.

    Our results indicate that ADMA is a strong marker for TIA and severe ICA stenosis, and that relative defiency of arginine, measured as L-arginine/ADMA, is present in acute CVD.

    We also conclude that a common polymorphism of the FABP2 gene increases susceptibility to ischaemic stroke and TIA.

  • 88.
    Weis, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ortiz-Nieto, Francisco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Assessment of lipids in skeletal muscle by LCModel and AMARES2009In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 30, no 5, 1124-1129 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To process single voxel spectra of the human skeletal muscle by using an advanced method for accurate, robust, and efficient spectral fitting (AMARES) and by linear combination of model spectra (LCModel). To determine absolute concentrations of extra- (EMCL) and intramyocellular lipids (IMCL). MATERIALS AND METHODS: Single-voxel proton magnetic resonance spectroscopy (PRESS) was used to obtain the spectra of the calf muscles. Unsuppressed water line was used as a concentration reference. A new prior knowledge for AMARES was proposed to estimate the concentrations of EMCL and IMCL. The prior knowledge was derived from the spectrum of vegetable oil. The results were compared with the values estimated by LCModel. Absolute concentrations of total lipid content in millimoles per kilogram wet weight were used for the comparisons. RESULTS: Absolute concentrations of total lipid content in skeletal muscle were estimated by AMARES and LCModel. Very good correlation of the total fat (EMCL + IMCL) and IMCL concentrations was achieved between both data processing approaches. CONCLUSION: Assessment the absolute concentrations of muscular lipids by AMARES and LCModel can be performed with comparable accuracy.

  • 89.
    Westergren, Jens
    University of Gävle, Department of Caring Sciences and Sociology.
    Sodium bicarbonate ingestion increases pH in blood but does not attenuate exercise induced arterial hypoxemia or enhance performance2008Independent thesis Advanced level (degree of Magister), 20 points / 30 hpStudent thesis
    Abstract [en]

    Introduction: The exact causes of Exercise Induced Arterial Hypoxemia (EIAH) are not yet known. Earlier studies on the ergogenic effects of NaHCO3 have neglected to investigate the occurrence of EIAH among their subject, something that could explain the conflicting results, EIAH cannot be over looked since reportedly 50% of well trained athletes experience EIAH. One possible ergogenic effect of NaHCO3 would be to attenuate EIAH through an increase in blood pH in a subject. This has been shown previously by means of intravenous infusion during maximal rowing.

    Aim: The aim of the study was to examine the effect of oral intake of NaHCO3 on EIAH and performance in trained cyclists.

    Method: Seven male cyclists (age 23.7 (22-27) years, VO2peak 64 (60-72) ml min-1 (kg body mass) -1 volunteered for the study. The subjects performed two maximal exercise tests to exhaustion 48 hours apart in a counter balanced cross over double blind fashion. Subjects received 0.3 g kg BW-1 CaCO3 and 0.3 g kg BW-1 NaHCO3 in the placebo and bicarbonate trial respectively.

    Free flowing arterialized capillary blood was sampled at rest and exhaustion and analyzed for pH, O2 Saturation, pO2, pCO2, and blood lactate. Ventilatory variables were measured continuously throughout the test V'O2, V’CO2, V'E, V'E/VO2, RER and HR. In addition pulse oximetry was used to evaluate O2 saturation.

    Results/Discussion: At rest pH and PCO2 was elevated (p<0.05) in the bicarbonate trial compared to the placebo trial. At exhaustion in the bicarbonate trial pH, blood lactate, RER, was significantly elevated (p<0.05) when compared to the placebo trial. O2 saturation from blood samples at exhaustion in the bicarbonate trial showed a trend towards improving (p=0.061). No difference was seen between the two trials in PO2, VO2peak, V'Emax, HRmax or performance. During exercise, bicarbonate ingestion increased blood pH but did not improve arterial saturation or performance. The increase in blood pH achieved by ingestion of bicarbonate was not as large as the increase achieved by intravenous infusion in another study. Even with the larger increase in blood pH in those studies, there was only a small improvement in performance. One possible explanation for the performance improvement with bicarbonate infusion in that study was a reduced ventilation that could effect respiratory muscle work and thereby work capacity. The bicarbonate ingestion in the present study did not reduce ventilation. This could possible be achieved with higher doses of NaHCO3, which would most likely result in increased frequency of gastrointestinal distress among subjects.

  • 90.
    Westin, Lars
    et al.
    University of Skövde, School of Life Sciences.
    Danielson, Ella
    Sahlgrens Acad, Inst Hlth & Care Sci, Gothenburg, Sweden / Mid Sweden Univ, Dept Hlth Serv, Östersund, Sweden.
    Encounters in Swedish nursing homes: a hermeneutic study of residents' experiences2007In: Journal of Advanced Nursing, ISSN 0309-2402, E-ISSN 1365-2648, Vol. 60, no 2, 172-180 p.Article in journal (Refereed)
    Abstract [en]

    Aim. This paper is a report of a study to illuminate and interpret the meaning of residents' experiences of encounters with nurses in nursing homes.

    Background. A large number of older people suffer from illness and become dependent on other people in their daily living. These people are often in need of care in nursing homes. It is assumed that encounters between nurses and residents are of importance in how residents experience care in nursing homes.

    Method. Twelve residents from three nursing homes in Sweden were interviewed in 2004–2005 about their experiences in encounters with nurses. The interviews were tape-recorded and transcribed verbatim. A hermeneutic method was used to describe and interpret the meaning of residents' experiences.

    Findings. Three themes emerged: 'being somebody', 'being nobody' and 'being in a community'. The encounters had both positive and negative influences on residents, expressed as being somebody and belonging somewhere or being nobody and not being seen as a person or simply being left out of things. Encounters between residents and nurses have a mutual dependency where residents certainly have some influence on the relationship. The nurses have both an influence on the relationship and a professional responsibility for the outcome of encounters with residents.

    Conclusion. The insights gained from the study can guide nurses in their encounters with residents in nursing homes so that they feel respected as unique human beings and part of a community.

  • 91.
    Wigert, Annsofi
    University of Gävle, Department of Caring Sciences and Sociology.
    Har syrgaskoncentrationen någon inverkan på lungfunktionen vid endotrakeal sugning och lungrekrytering?: En experimentell studie på gris2008Independent thesis Advanced level (degree of Magister), 20 points / 30 hpStudent thesis
    Abstract [en]

    INTRODUCTION

    One of the most common routines in mechanically ventilated patients is endotracheal suction,

    (ETS). To avoid desaturation connected to this routine, it is common to increase oxygen

    concentration for a few minutes. High fractions of oxygen can be damaging, and it causes

    athelectasis which impairs gas exchange in the lung. A physiological respond due to the

    athelectasis is redirecting the bloodstream from poorly ventilated lungparts which leads to an

    increased pulmonary pressure. The aim of this study was to investigate if preoxygenation and

    lung recruitment with different oxygen concentrations influences hemodynamics, lung mechanics

    and lung volume.

    METHOD

    In six anaesthetised pigs with assisted mechanical ventilation preoxygenation was given with

    100 % or 60 % O2 for 5 minutes and followed by suction in the endotracheal tube. Thereafter, in

    3 out of 4 protocols a deep sigh was delivered with 21 %, 60 % or 100 % O2 at a pressure 15

    cmH2O above plateau pressure. Hemodynamics and lung mechanics were measured. For control

    in the studie no lungrecruitment was performed in one of the protocols.

    RESULTS

    Mean pulmonary pressure was induced in the protocol where there was no regain of lung volume

    after suction, 29±3 mmHg compared to bas line value of 22±2 mmHg (p<0.05). There was a clear

    difference in lung compliance, whether the lung volume was recruited, 22±1 (100 % O2), 21±3

    (21% O2), 21±3 (60 % O2) or not recruited, (13±1 mL cmH2O) after suction (p<0.001). The same

    were seen for changes in VT (p<0.001) and EELV (p<0.05).

    CONCLUSION

    The oxygen concentration when performing endotracheal suctioning is in this experimental

    model of no influence regarding hemodynamics, lung mechanics- or lung volumes, provided

    recruitment of the lung is done directly after suctioning.

  • 92.
    Winberg, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nordström, Lisbeth
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Strinnholm, Åsa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Nylander, Annica
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Jonsäll, Anette
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Rönnmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    West, Christina E.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    New validated recipes for double-blind placebo-controlled low-dose food challenges2013In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 24, no 3, 282-287 p.Article in journal (Refereed)
    Abstract [en]

    Double-blind placebo-controlled food challenges are considered the most reliable method to diagnose or rule out food allergy. Despite this, there are few validated challenge recipes available. The present study aimed to validate new recipes for low-dose double-blind placebo-controlled food challenges in school children, by investigating whether there were any sensory differences between the active materials containing cow's milk, hen's egg, soy, wheat or cod, and the placebo materials. The challenge materials contained the same hypoallergenic amino acidbased product, with or without added food allergens. The test panels consisted of 275 school children, aged 810 and 1415yr, respectively, from five Swedish schools. Each participant tested at least one recipe. Standardized blinded triangle tests were performed to investigate whether any sensory differences could be detected between the active and placebo materials. In our final recipes, no significant differences could be detected between the active and placebo materials for any challenge food (p>0.05). These results remained after stratification for age and gender. The taste of challenge materials was acceptable, and no unfavourable side effects related to test materials were observed. In summary, these new validated recipes for low-dose double-blinded food challenges contain common allergenic foods in childhood; cow's milk, hen's egg, soy, wheat and cod. All test materials contain the same liquid vehicle, which facilitates preparation and dosing. Our validated recipes increase the range of available recipes, and as they are easily prepared and dosed, they may facilitate the use of double-blind placebo-controlled food challenges in daily clinical practice.

  • 93.
    Yaraghi, Niam
    KTH, School of Engineering Sciences (SCI), Mechanics.
    Critical Success Factors for Risk Management Systems2009Independent thesis Advanced level (degree of Master (One Year)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Despite the existence of extensive literature regarding risk management, there still seems to be lack of knowledge in identification of Critical Success Factors (CSFs) in this area. In this research Grounded Theory is implemented to identify CSFs in Risk Management Systems (RMS). Factor analysis and one-sample t-test are then used to refine and rank the CSFs based on the results of a survey which has been performed among Risk Management practitioners in various types of Swedish corporations. CSFs are defined from three different perspectives: (a) the factors that have influence on the inclination and readiness of corporation for implementing RMS. (b) the factors that are important during the design and implementation of RMS in corporation and can significantly affect the success of RMS design and implementation and (c) the factors that are crucially important to successfully run, maintain and administrate RMS after the closure of the project of RMS design and Implementation.

    This systematic approach towards understanding the taxonomy of the success dimension in RMS is important for re-enforcing effective risk management practices.

  • 94.
    Zeisig, Eva
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Sports Medicine.
    Tennis elbow: sonographic findings and intratendinous injection treatment2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Tennis elbow (TE) is a relatively common painful condition affecting the upper extremity. The aetiology is not known, but TE is most often seen in middle aged individuals using repetitive and forceful gripping at work or recreational activities, and is referred to overuse injuries. The pathogenesis is not known, but there are so-called degenerative changes in the wrist- and finger-extensor muscle origin (common extensor origin - CEO). The pain mechanisms involved have not been scientifically clarified.

    The studies in the present thesis aimed to 1) evaluate the structure and blood flow using ultrasound (US) and colour Doppler (CD) examinations of the CEO in patients with TE, and in pain-free elbows, 2) evaluate the clinical effects of US- and CD-guided intratendinous injection treatment with the sclerosing substance polidocanol, 3) evaluate the long term (2 years) effects of injection treatment on the tendon structure and blood flow, and 4) investigate if there is a local production of sympathetic and parasympathetic signal substances in non-neural cells in the CEO.

    Structural tendon changes and high blood flow was found in the CEO in patients with TE, but not in pain-free controls. Remaining structural changes and additional bone spur formation at the lateral epicondyle, but not high blood flow, were seen 2 years after successful injection treatment. In a randomised double-blind study, US- and CD-guided intratendinous injection treatment with sclerosing polidocanol or the local anaesthetic lidocaine combined with epinephrine, targeting the region with high blood flow, was found to reduce pain and increase grip strength in patients with TE. There were no differences in the outcome between the two treatment groups. A local production of catecholamines, but not acetylcholine, was found in fibroblasts in the CEO, in patients with TE.

    This thesis presents results showing US and CD examinations to be useful methods to diagnose TE, and to evaluate structure and blood flow in the CEO after treatment. US- and CD-guided injection treatment targeting high blood flow in the region with structural changes can reduce pain symptoms in patients with TE. The localised high blood flow, and local production of catecholamines in the tendon cells in the CEO, might be involved in the pain mechanisms.

  • 95.
    Zetterqvist, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Non-Suicidal Self-Injury in Swedish Adolescents: Prevalence, Characteristics, Functions and Associations With Childhood Adversities2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Non-suicidal self-injury (NSSI), such as intentionally cutting, burning or hitting oneself, is a behavior with potentially detrimental consequences and empirical studies are necessary to gain knowledge of how to prevent NSSI in adolescents. The aims of this thesis were to investigate the prevalence, methods, characteristics and functions of NSSI in a large community sample of Swedish adolescents, and to examine the relationship between NSSI and adverse life events and trauma symptoms. All empirical studies had a cross-sectional design and were based on 3,097 adolescents in the county of Östergötland, aged 15-17 years, in their first year of high school. Participating school classes were selected through a randomization process and administered self-report questionnaires.

    In study I (n = 3,060) a single item NSSI question resulted in a prevalence rate of 17.2%, while 35.6% of adolescents reported having engaged in NSSI at least once during the past year when given a checklist. The most commonly reported type of NSSI in this sample was “bit yourself”, followed by “hit yourself on purpose”, “erased your skin” and “cut or carved on your skin”. Applying the proposed DSM-5 diagnostic criteria of NSSI resulted in a prevalence rate of 6.7%. Results in study II (n = 2,964) showed that after controlling for gender, parental occupation and living conditions, adolescents with no self-injurious behavior reported the lowest level of adversities and trauma symptoms, while adolescents with both NSSI and suicide attempts (5.7%) reported the highest levels compared to those with only NSSI or a suicide attempt. Adolescents reporting frequent NSSI reported more adversities and trauma symptoms than those with less frequent NSSI. Automatic functions, such as affect regulation, self-punishment and feeling-generation, were the most commonly reported functions of NSSI. Attempts in study I to confirm Nock and Prinstein’s (2004) four-factor model of underlying factors of NSSI functions resulted in a close to acceptable fit. An attempt to refine the factor analysis on this community sample of Swedish adolescents, using Mplus with cross-validation, was made in study III (n = 836). An exploratory factor analysis resulted in a three-factor model (social influence, automatic functions and non-conformist peer identification), which was validated in confirmatory analysis. In order to adhere more closely to learning theory and the concept of negative and positive reinforcement, the third factor was then split into two factors, resulting in a four-factor model (social influence, automatic functions, peer identification and avoiding demands), which showed excellent fit to the data in the confirmatory factor analysis. Study IV (n = 816) showed that NSSI frequency, gender (female), self-reported experience of emotional and physical abuse, having made a suicide attempt, prolonged illness or handicap and symptoms of depression and dissociation were significant predictors in the final model of the automatic functions, indicating that these variables are important in understanding the mechanisms underlying the need to engage in NSSI to regulate emotions, generate feelings, gain control or to self-punish. Symptoms of depression and dissociation mediated the relationship between sexual, physical and emotional abuse and the automatic  functions. Furthermore, frequency of NSSI, gender, emotional abuse, prolonged illness or handicap and symptoms of depression uniquely predicted automatic functions but not social functions. Self-reported experience of physical abuse, having made a suicide attempt, symptoms of anxiety and dissociation were significant in the final model of social functions, i.e., performing NSSI to influence or  communicate with others, to avoid demands or to identify with peers. Of these, symptoms of anxiety were uniquely associated with social functions. Symptoms of anxiety and dissociation mediated the relationship between physical abuse and social functions of NSSI.

    Taken together, this thesis has shown that NSSI is prevalent in Swedish adolescents and findings contribute to the discussion of a potential NSSI diagnosis. It is important to consider the effect of different types of negative life events and trauma symptoms in relation to NSSI in adolescents. Assessing the specific reinforcing functions of NSSI and the underlying factor structure can be helpful in developing functionally relevant individualized treatment.

  • 96.
    Zineldin, Mosad
    Växjö University, Faculty of Humanities and Social Sciences, School of Management and Economics. marknadsföring.
    cooperation, competition and health care refrom: Challenges and opportunities for health care officials, professionals and patents2007Conference proceedings (editor) (Other (popular science, discussion, etc.))
  • 97.
    Åkerman, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Aspects of the Pre-Diabetic Period in Type 1 Diabetes2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Type 1 diabetes (T1D) is an autoimmune disease characterized by insulin deficiency, due to immune-mediated destruction of beta cells. Current knowledge regarding the period preceding disease onset comes, to a large extent, from studying risk cohorts based on relatives of T1D-patients, as they have an increased disease risk. Among T1D patients in general, however, few have the disease in their immediate family. It is therefore important to study risk cohorts from the general population as well. An ongoing autoimmune reaction can often be seen in the blood long before disease onset, by detection of autoantibodies directed towards beta cell antigens. By autoantibody screening among participants in the ABIS (All Babies in the South-east of Sweden) cohort, we could identify a group of children from the general population with increased risk for T1D, positive for multiple autoantibodies. They were enrolled in a 2-year prospective follow-up aiming to characterize the prediabetic period and to identify factors indicative of progression/non-progression to T1D. We assessed glucose homeostasis and autoantibody titers over time, and searched for risk-biomarkers by analyzing the expression of immune-related genes (Th1-Th2-Th3) in peripheral blood mononuclear cells (PBMC) from these children, in comparison to healthy children and newly diagnosed T1D patients. In the same groups we also compared serum micro RNA (miRNA) profiles, knowing that miRNA molecules have desirable biomarker properties. We found that two specific autoantibodies, IA2A and ZnT8A, were detected at higher concentrations in risk-individuals who progressed to overt T1D during or after the follow-up period, compared to those who still have not. We also observed disturbed glucose homeostasis long before onset in the progressors, but it was seen among those who remain symptom free as well. Further, we found support for the possible role of insulin resistance as an accelerator of the disease process. For gene expression and serum miRNA, few differences were observed between risk-individuals and healthy children overall. However, for PBMC gene expression and serum miRNA both, there were associations to beta cell function and glucose homeostasis, and for miRNA also to islet autoantibodies. Although specific profiles for prediction of disease onset or identification of risk-individuals could not be found, these results are interesting and deserve to be evaluated further. As part of another sub-study within ABIS, the effects of physical activity on glucose homeostasis were assessed in healthy schoolchildren. The level of physical activity, measured by pedometers, was related to insulin resistance and beta cell-stress, and decreased physical activity was associated with increased insulin resistance and load on the insulin-producing beta cells, already at school-age.

12 51 - 97 of 97
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