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  • Adolfsson, Per, 1967- (författare)
  • Regulatory importance of cyclic nucleotides in smooth muscle growth of the urogenital tract
  • 2001
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Smooth muscle hyperplasia/hypertrophy is, if not responsible for, so at least involved in those diseases, which impair life quality for most people in today's society.</p><p>This thesis, presents a pharmacological investigation, related to the regulatory role of cyclic nucleotides, of smooth muscle hyperplasia/hypeitrophy in human uterine leiomyoma and benign prostate hyperplasia (BPH).</p><p>Four main aspects, with cAMP as a connecting thought, have been analyzed, namely expression and characterization of the adrenergic receptors (AR), determination of adenylyl cyclase (AC)- and phosphodiesterase (PDE)-activity, and finally the connection between mentioned issues and proliferation of cultured smooth muscle cells (smc).</p><p>In the frrst paper, characterization of the a 2-adrenergic receptor (az-AR) subtypes in human myometrium at term pregnancy was examined by combining radioligand binding-studies with reverse transcriptase-polymerase chain reaction (RT-PCR). Results demonstrated a significant eo-expression of α<sub>2A</sub> and α<sub>2B</sub>, and a weak indication of the α<sub>2C</sub>-AR, which however was identified at the mRNA level by the RT-PCR analysis.</p><p>In the next investigatio~ smooth muscle tissue of human uterine leiomyoma (benign smooth muscle tumor) was compared with surrounding myometrial tissue (control). The expression of AR, AC- and PDE-activity was analyzed, as well as the effect of cAMP with respect to growth regulation of cultured leiomyoma smc. Primarily, a significantly reduced ß<sub>2</sub>-AR expression and AC-activity was detected in leiomyoma compared to control tissue, whereas the PDE-activity was approximately 100% higher. In addition, the α<sub>2</sub>-AR population in leiomyoma was slightly increased. When cultured leiomyoma smc was treated with cAMP increasing agents as forskolin, an AC stimulating agent, or papaverin, a general PDE inhibitor, a considerable inhibition of DNA replication and protein synthesis was obtained.</p><p>In the thh·d paper, a proliferation study was made on cultured benign prostate hyperplasia smc, were the mitogen effect of lysophosphatidic acid (LPA) and cAMP/cGMP increasing agents was investigated. LPA generated a dose-dependent mitogen response, which was efficiently inhibited, both by forskolin, and by papaverin. In addition, sildenafil (Viagra®), which serve as a potent and selective PDE5 inhibitor, also decreased the LPA mediated growth promotion in a dose dependent manner.</p><p>The last study, demonstrate primarily the expression pattem of LPA receptors (Edg) in BPH smc. Further, the intracellular cAMP changes in LPA stimulated BPH smc and the proliferative effect of the LPA analogue sphingosine 1-phosphate (SIP) was considered. First, all Edg was identified with exception of Edg6. Moreover, the cAMP level was unchanged by LPA <em>per se</em>, whereas co-incubation with forskolin generated a rapid and transient response. Further, SIP generated a divergent response including a LPA equivalent mitogen effect at low concentrations whereas inhibition of DNA replication was obtained at higher concentrations.</p><p>In summary, this project demonstrates that cyclic nucleotides inhibit smooth muscle hyperplasia/hypertrophy in the luogenital tract. These results also suggest that manipulation of cyclic nucleotide level using tissue specific PDE inhibitors might constitute a new therapeutic approach for hyperplasia/hypertrophy related diseases in the urogenital tract.</p>
  • af Klercker, Tom (författare)
  • Method for inductive case-based decision support system over the Internet : exemplified by ear, nose and throat diagnostics in primary care
  • 1997
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>This thesis is an example of an ear to loaf process:</p><p>A Preliminary Essential Data Set (PEDS) for Ear, Nose and Throat (ENT) diagnostics in Primary Health Care (PHC) was established by infologic modelling of existing tractates, between the specialist organisations of ENT and PHC, and four contemporary text-books on the subject (I). The PEDS was then compared to the aggregated data from a sample of case-files from a Swedish PHC centre. The quality of the individual medical record was found to be poor and not sufficient for follow-up and Quality Management (QM) purposes (II). The aggregated data from the case-file sample was processed by an inductive "expert" computer program that generated a decision-tree, based on the total number of decisions (diagnoses) in the data-base. This was nearly identical to the PEDS and somewhat less complicated. Infological modelling of the PEDS and the decision-tree resulted in the proposed Essential Data Set (EDS) for ENT diagnostics in PHC. The decision tree was "pruned" to achieve simplicity and ease of use (III). It was converted into a Computer-aided Decision Support System (CDSS) and put on the Internet using World Wide Web (WWW) tools (IV). This system was then implemented in the Skänninge PHC centre where an Electronic Medical Record System (EMRS) was in everyday use. Due to technical difficulties no integration between the two systems was possible. The CDSS was run on a computer outside the centre and this raised the question of secrecy and security (V). Prior to the implementation, and after a study period of four months attitudes towards, and the acceptance of, new Information Technology (IT) was explored by using focus group methodology (VI). It is important that those who are to use the system are intimately involved in its development. The results showed, that participation of the end-users during implementation is crucial for its acceptance. The need for a uniform and agreed terminology was obvious to facilitate co-operation and QM. The importance of nurses and physicians using the same terminology for documentation, was paramount.</p>
  • Afoke, Anthony Okoro (författare)
  • Some epidemiological aspects of insulin-dependent diabetes mellitus in Nigeria and Sweden
  • 1993
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>In the western world diabetes mellitus is one of the most common severe diseases in childhood, but it is rarely seen in black African populations. However, there are very few epidemiological studies of childhood diabetes in Africa and almost nothing is known of the Nigerian population. One aim of this study was therefore to estimate the prevalence of insulin dependent diabetes (IDDM) in children and adolescents and to characterize their type of diabetes.</p><p>A screening of almost 78,000 school children was performed and beside some already known diabetic patients several new cases were diagnosed. It was found that IDDM is much less common than in Europe but on the other hand more common than in several Asian countries. In addition the prevalence found may be underestimated because of cultural and social factors, health care problems and high mortality in diabetes. Although most patients had a clinical picture of Malnutrition Related Diabetes (MRD) we found in some cases autoantibodies towards islet cells and insulin and furthermore the same HLA-DQ-type-associations as seen to Type 1 diabetes in caucasian diabetics.</p><p>While we saw no seasonal variation of diagnosis of Nigerian IDDM, there is a pronounced such seasonal variation in Sweden. This study has tried to elucidate whether this seasonal variation is related to any differences in manifestation and clinical course. Patients diagnosed during incidence peaks had more often short duration of symptoms before diagnosis,ketonuria at diagnosis, rapid loss of endogenous insulin secretion but increase of insulin antibodies and of glycosylated haemoglobin. They had also more often infections before diagnosis and high serum immunoglobulins (IgG and IgM) up to 9 months after diagnosis. HLA-DR4 was more common in these patients. The results suggest that IDDM in Swedish children is heterogenous.</p>
  • Afrell, Maria, 1953- (författare)
  • Att leva med en kropp som värker samtal med fysioterapeuten
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p><strong>Bakgrund och syfte:</strong> Fysioterapeuter i primärvården möter, bedömer och behandlar patienter med långvarig benign muskuloskeletal smärta. Tillståndet är vanligt och men likafullt komplext. Syftet med detta avhandlingsarbete har varit att i ett kroppsligt existentiellt perspektiv utforska och begreppsliggöra upplevelsen av att leva med långvarig benign muskuloskeletal smärta samt att utifrån detta utveckla en metod för samtal och bedömning inom icke specialiserad fysioterapi.</p><p><strong>Metoder:</strong> Arbete I var en intervjustudie med fenomenologisk ansats där vi undersökte hur individer med långvarig smärta upplevde sin kropp och sina besvär. Fyra aspekter av kroppsupplevelsen beskrevs och ur dessa urskildes fyra klart åtskilda typologier av förhållningssätt. I arbete II gjorde vi två gruppintervjuer med sex fysioterapeuter om deras erfarenheter av att i kliniskt arbete använda frågor – nyckelfrågor - ur frågeguiden i arbete I som givit särskilt rika svar. Utskrifterna av gruppintervjuerna analyserades med fenomenografisk ansats. I arbete III undersöktes patienters svar på nyckelfrågorna, ställda av fysioterapeuter under kliniskt arbete, och de fyra aspekterna av kroppsupplevelse från arbete I utgjorde begrepp för en deduktiv analys. I arbete IV slutligen prövades nyckelfrågorna och  typologierna av en större grupp (31) fysioterapeuter i primärvården och deras erfarenheter och den möjliga användbarheten av metoden studerades. En kvalitativ innehållsanalys med beräkning av koder användes.</p><p><strong>Resultat:</strong> Vi skapade fyra typologier av förhållningssätt till långvarig smärta: Acceptera sitt öde, acceptera genom aktiv förändring, befinna sig mellan acceptans och avståndstagande eller ta avstånd från sin värkande kropp. Dessa typologier byggdes upp av fyra aspekter av kroppsupplevelse: Kroppen som en aspekt av identiteten, kroppstillit, kroppsmedvetenhet samt förståelse av sin smärta. I arbete II visade det sig möjligt att tillsamman patient och fysioterapeut, med hjälp av nyckelfrågorna, föra ett kroppsligt existentiellt samtal. I samtalen lärde fysioterapeuten känna patienten som person, det föreföll som att en process inom patienten satte igång, samt att deras relation förändrades. Patienten var villig att samtala om sin värkande kropp och hade ord för detta. I studie III banade nyckelfrågorna väg för reflektioner om kropp, existens och biografi. De fyra aspekterna av kroppsupplevelse hade en central plats i patienternas beskrivningar. I arbete IV beskrev de deltagande sjukgymnasterna överlag positiva erfarenheter av att använda nyckelfrågor och typologier. Patienterna reflekterade, känslor väcktes och relationen och kommunikationen förbättrades ofta. Typologierna hjälpte till att få ett helhetsperspektiv på patientens problematik och att förstå var patienten befann sig i rehabiliteringsprocessen, vilket kunde vara värdefull vid bedömning och val av behandling.</p><p><strong>Konklusion:</strong> Metoden, sju nyckelfrågor tillsammans med den erbjudna möjliga referensramen för tolkning av svaren (de fyra typologierna), förefaller lätt att ta till sig för intresserade fysioterapeuter i icke specialiserad verksamhet.Användandet av metoden belyser vikten av en utvidgning av fysioterapeutrollen. Utmaningen är att möta hela människan, som är sin levda kropp såväl som sin identitetskris buren av känslor som sorg och ilska. Detta kan sporra till att fullt ut utnyttja de möjligheter i mötet med patienten som den fysioterapeutiska yrkesrollen omfattar.</p>
  • Agholme, Fredrik (författare)
  • Wnt signaling and metaphyseal bone healing
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>This thesis relates to some new aspects on the regulation of bone healing. In the last few years, Wnt-signaling has been shown to play a central role in bone biology. As well as being involved in bone maintenance and repair, Wnt-signaling has been presented as one of the key pathways through which bone responds to mechanical load. Two secreted extracellular inhibitors of Wnt-signaling, sclerostin and dickkopf-1 are potent negative regulators of bone formation.</p><p>Using a rat fracture model we investigated how metaphyseal bone healing is influenced by changes in Wnt-signaling.</p><p>Antibodies were used to suppress levels of sclerostin and dickkopf-1, and thereby increase Wnt-signaling. Primarily, we investigated if those antibody treatments lead to improved bone healing. Also, we investigated if the response was coupled to the loading conditions of the bone.</p><p>Our findings suggest that suppression of either sclerostin or dickkopf-1 leads to increased bone formation and improved bone healing. Apart from just having an effect on healing, the treatment also improved bone formation in other parts of the skeleton. Depending on the loading conditions, the effects were different. Dickkopf-1 appeared to have a stronger effect on bone volume density in unloaded bone, implying a role mainly in mechano-transduction, while sclerostin had similar effect in both loaded and unloaded bone. To confirm these findings, we studied how the expression of several Wnt-related genes changed due to trauma and unloading in metaphyseal bone. We found that trauma led to upregulation of most of the genes with the largest effect seen in the unloaded bone. In untraumatized bone, there was mainly an effect on the sclerostin gene.</p><p>In conclusion, antibodies against sclerostin and dickkopf-1 appear to be able to improve metaphyseal bone healing. There appear to be some differences in how the effect of the two antibodies manifests itself, especially if the loading conditions of the bone are altered. These findings suggest a potential for clinical use to shorten fracture healing time.</p>
  • Agholme, Lotta (författare)
  • The involvement of degradation pathways and neuron-to-neuron transmission in Alzheimer’s disease
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Although the vast majority of Alzheimer’s disease (AD) cases are of the sporadic type, mutations causing the familial form have been the focus of AD research for decades. The disease is pathologically characterised by β-amyloid (Aβ) and tau protein aggregates in neuritic plaques and neurofibrillary tangles. Furthermore, it is known that AD pathology spreads throughout the brain, most often along the same anatomical pattern. However, so far no cause for the sporadic form of the disease has been found. Accumulation of protein aggregates as well as decreased activity of the protein degradation systems, lysosomes and proteasomes, is found in diseased brains. This indicates that defective degradation contributes to sporadic AD.</p><p>The aim of this thesis was to develop an improved neuronal model, and study the effects of decreased proteasome function on tau phosphorylation and axonal transport. In addition, the effects on Aβ accumulation and generation upon proteasome inhibition were investigated. Finally, the possibility that intracellularly accumulated Aβ oligomers could be transferred from one neuron to another was tested.</p><p>Differentiation of human SH-SY5Y neuroblastoma cells in an extracellular matrix gel, using a set of neurotrophic factors, resulted in cells with neuronal phenotype, expressing neuron specific markers and all six adult isoforms of tau. Within this neuronal model, we found that reduced proteasome activity inhibited neuritic transport, and caused tau phosphorylation in a c-Jun and ERK 1/2 dependent manner. Using proteasome inhibition in APP overexpressing cells, we found an autophagy dependent intralysosomal Aβ accumulation, together with elevation of intra- and extracellular concentrations of Aβ. Autophagy inhibition protected the cells from the toxicity induced by decreased proteasome activity. Finally, we could, as the first group, show that Aβ can be directly transferred from one neuron to another through connected neurites. Furthermore, accumulation of Aβ in the endo-lysosomal compartment of receiving cells caused toxicity and neurodegeneration.</p><p>We believe that cells not able to degrade accumulated Aβ, due to increased generation or reduced degradative capacity, instead tries to clear its content through transfer to connected neurons. If not properly degraded in the receiving cell, this can accelerate AD pathology and cause neuritic and neuronal degeneration spreading throughout the brain. Increasing the activity of the degradative systems, or inhibiting transmission of Aβ between neurons could therefore be novel treatments for AD.</p>
  • Agnafors, Sara, 1981- (författare)
  • A Biopsychosocial and Long Term Perspective on Child Behavioral Problems Impact of Risk and Resilience
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Mental health has become a prominent issue in society. Yet, much remains unknown about the etiology of psychiatric disorders. The aim of the present thesis was to investigate the association between biological, psychological and social factors of risk and resilience and behavioral problems in a birth cohort of Swedish children. 1723 mothers and their children were followed from birth to the age of 12 as part of the South East Sweden Birth Cohort Study (the SESBiC study). Information was gathered through register data, standardized questionnaires and DNA samples.</p><p>In study I, stability of maternal symptoms of depression and the impact on child behavior at age 12 were investigated. The prevalence of depressive symptoms was found to be 12.0 % postpartum. Symptoms of postpartum depression significantly increased the risk for subsequent depressive symptoms 12 years later in women. Children whose mothers reported concurrent symptoms of depression and anxiety had an increased risk for both internalizing and externalizing problems at age 12, but no long term effect on child behavior was seen for postpartum depressive symptoms. The greatest risk was seen for children whose mothers reported symptoms of depression on both occasions. In study II, the impact of gene-environment interaction of 5-HTTLPR and BDNF Val66Met and experience of life events together with symptoms of maternal depression and anxiety on child behavior at age 12 was studied. A main effect of 5-HTTLPR was noticed, but no geneenvironment effects were shown. Similarly to study I, concurrent symptoms of maternal depression and anxiety were an important predictor of child behavioral problems. A high degree of psychosocial stress around childbirth was found to have long lasting detrimental effects on child behavior, increasing the risk for internalizing problems at age 12. Study III investigated the impact of geneenvironment interactions of 5-HTTLPR and BDNF Val66Met and life events together with symptoms of maternal depression and birth characteristics on behavioral problems at age 3. Symptoms of postpartum depression were found to predict internalizing as well as externalizing problems in children three years later. Child experience of life events was a stable predictor of behavioral problems across the scales similar to sociodemographic factors such as parental immigration status and unemployment. No gene-environment interaction effects of 5-HTTLPR or BDNF Val66Met were shown. Study IV used the risk factors identified in studies I-III to investigate factors of resilience to behavioral problems at age 12. The l/l genotype of 5-HTTLPR was associated with a lower risk for behavioral problems at age 12, especially for children facing low adversity. Good social functioning was found to be a general resource factor, independent of the level of risk, while an easy temperament was associated with resilience for children with a high degree of adversity. However, effect sizes were small.</p><p>In summary, the results from the present thesis emphasize the importance of maternal mental health and sociodemographic factors for child mental health at ages 3 and 12, which must be taken into account in clinical settings. Moreover, it adds to the null-findings of the gene-environment effect of 5-HTTLPR and BDNF Val66Met on behavioral problems in children, but indicates a main effect of 5-HTTLPR on internalizing symptoms at age 12.</p>
  • Agvall, Björn, 1963- (författare)
  • Heart failure in primary care with special emphasis on costs and benefits of a disease management programme
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p><strong>Background and aim.</strong> Heart failure (HF) is a common condition associated with poor quality of life (QoL), high morbidity and mortality and is frequently occurring in primary health care (PHC). It involves a substantial economic burden on the health care expenditure. There are modern pharmacological treatments with evident impact on QoL, morbidity, mortality, and proved to be cost-effective. Despite this knowledge, the treatment of HF is considered somewhat insufficient. There are several HF management programmes (HFMP) showing beneficial effects but these studies is predominantly based in hospital care (HC).</p><p>The first aim of this thesis was to describe patients with HF in the PHC regarding gender differences, diagnosis, treatment and health related costs (I, II).The second aim was to evaluate whether HFMP have beneficial effects in the PHC regarding cardiac function, quality of life, health care utilization and health care-related costs (III,IV).</p><p><strong>Methods.</strong> The initial study involved retrospective collection of data from 256 patients with symptomatic HF in PHC (I). The data collected were gender, age, diagnostics and ongoing treatment. The second study was an economic calculation performed on 115 patients (II). The economic data was retrospectively retrieved as the number of hospital days, visits to nurses and physicians in HC and PHC, prescribed cardiovascular drugs and performed investigation during retrospectively for one year. The third and fourth study was based on a randomized, prospective, open-label study which was subsequently performed (III,IV). The study enrolled 160 patients with systolic HF who were randomized to either an intervention or a control group. The patients in the intervention group retrieved follow-up of HF qualified nurses and physicians in the PHC, involving education about HF and furthermore, optimizing the treatment according to guidelines if possible. The patients in the control group had a followup performed by their regular general practitioner (GP) receiving customary management according to local routines but there was no contact with HF nurses. The primary endpoint of the study was a composite endpoint consisting of changes in survival, hospitalization, heart function and quality of life (QoL) and to compare differences in resource utilization and costs (III,IV).</p><p><strong>Results.</strong> In the first study, the prevalence was 2% and the average age was 78 years (I). The most frequent cause of HF was IHD followed o hypertension. The diagnosis in the study population was based on clinical criteria and only 31% had been subjected to echocardiography. The most common treatment was diuretics (84%) and angiotensin converting enzyme inhibitors (ACEI) were used in 56% of patients. In the following prospective study, the intervention group had significant improvements in composite endpoints. There were in the intervention group more patients with reduced levels of NTproBNP (p=0.012) and improved cardiac function (p=0.03). No significant changes were found in New York Heart Association (NYHA) functional class or QoL. The intervention involved less health care contacts (p=0.04), less emergency ward visits (p=0.002) and hospitalizations (p=0.03). The total cost for HC and PHC was EUR 4471 in the intervention group and EUR 6638 in the control group which implies a cost reduction of EUR 2167 (33%).</p><p><strong>Conclusions.</strong> HF is common in PHC with a prevalence of 2% the study population had an average age of 78 years. Only 31 % of the HF patients have performed an echocardiographic investigation. Treatment with ACEI occurred in 56 %. Differences were found between genders since women had performed significantly fewer echocardiographic investigations and, had less treatment with ACEI. When implementing HFMP in PHC, beneficial effects were found regarding cardiac function and health care-related costs in patients with systolic HF. These findings indicate that HFMP might be used even in PHC.</p>
  • Ahl, Ing-Marie, 1974- (författare)
  • Protein Engineering of Extracellular Superoxide Dismutase Characterization of Binding to Heparin and Cellular Surfaces
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Accumulating evidence indicates that oxygen free radicals are involved in many diseases and pathological conditions, such as aging, inflammation, reperfusion damage of ischemic tissue and various cardiovascular diseases. Extracellular superoxide dismutase (ECSOD) thus plays a major role in the maintenance of cells by providing protection against these toxic substances in the extracellular space. Various animal studies have shown that ECSOD has the ability to protect against many of these disorders, and interest has therefore evolved in the potential therapeutic use of the enzyme.</p><p>However, despite strenuous efforts, large-scale production of the enzyme has not been achieved. To overcome this problem, a mimic of the enzyme, PseudoECSOD, has previously</p><p>been constructed. This chimera is easy to produce in large amounts and has all the structural, enzymatic and heparin-binding characteristics of ECSOD, making it a potential substitute for ECSOD in therapeutic situations. However, the copper content of PseudoECSOD has been shown to be rather low, and since the copper ion is very important for the catalytic function of the enzyme, a production system that utilizes a copper chaperone for proper insertion of copper into the active site of the enzyme was constructed. The results show that the copper content of PseudoECSOD produced by this system is close to 100 %.</p><p>In order to use PseudoECSOD therapeutically, further investigations of its binding capability and protective properties are needed. Therefore, the binding of ECSOD and PseudoECSOD to heparin was investigated using isothermal titration calorimetry. The results show that although some purely ionic interactions are important for the binding between ECSOD and heparin, there is also a substantial contribution from non-ionic interactions. The investigation also showed that the C-terminal domain is the only part of ECSOD that contributes to productive binding, and that the binding of PseudoECSOD and ECSOD to heparin is similar.</p><p>In addition, analysis of mutant proteins strongly indicated that the amino acids R210, K211 and R214 are important for optimal binding of ECSOD to heparin, accounting for about 30 % of the total binding energy. The structural placement of these amino acids in an α-helix also confirms the hypothesis postulated by Margalit et al., that a common structural motif for heparin-binding proteins may be two positively charged amino acids at a distance of approximately 20 Å in the 3D-structure, facing opposite directions of a α-helix. The importance of these residues was also confirmed by analysis of a phage display library of the C-terminal domain of ECSOD.</p><p>The binding of PseudoECSOD to heparan sulfate on cell surfaces of two different cell types, HepG2 and endothelial cells, was also investigated. The results clearly show that PseudoECSOD binds to these cells in a very similar manner to ECSOD. To investigate the protective properties of PseudoECSOD against ischemia-reperfusion injuries, an isolated rabbit heart model was used. The results indicate that the enzyme has a protective effect. However, more experiments using the rabbit heart and other animal models are needed to identify the optimal dose for protective purposes. The protective properties of PseudoECSOD in human tissue should also be thoroughly investigated.</p><p>In summary, the findings in these studies, together with earlier results showing the close resemblance of PseudoECSOD to ECSOD in structural, enzymatic and heparin-binding properties, further support the proposition that PseudoECSOD may be a good substitute for ECSOD to use in therapeutic interventions.</p>
  • Ahlander, Britt-Marie, 1954- (författare)
  • Magnetic Resonance Imaging of the Heart Image quality, measurement accuracy and patient experience
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p><strong>Background:</strong> Non-invasive diagnostic imaging of atherosclerotic coronary artery disease (CAD) is frequently carried out with cardiovascular magnetic resonance imaging (CMR) or myocardial perfusion single photon emission computed tomography (MPS). CMR is the gold standard for the evaluation of scar after myocardial infarction and MPS the clinical gold standard for ischemia. Magnetic Resonance Imaging (MRI) is at times difficult for patients and may induce anxiety while patient experience of MPS is largely unknown.</p><p><strong>Aims:</strong> To evaluate image quality in CMR with respect to the sequences employed, the influence of atrial fibrillation, myocardial perfusion and the impact of patient information. Further, to study patient experience in relation to MRI with the goal of improving the care of these patients.</p><p><strong>Method:</strong> Four study designs have been used. In paper I, experimental cross-over, paper (II) experimental controlled clinical trial, paper (III) psychometric crosssectional study and paper (IV) prospective intervention study. A total of 475 patients ≥ 18 years with primarily cardiac problems (I-IV) except for those referred for MRI of the spine (III) were included in the four studies.</p><p><strong>Result:</strong> In patients (n=20) with atrial fibrillation, a single shot steady state free precession (SS-SSFP) sequence showed significantly better image quality than the standard segmented inversion recovery fast gradient echo (IR-FGRE) sequence (I). In first-pass perfusion imaging the gradient echo-echo planar imaging sequence (GREEPI) (n=30) had lower signal-to-noise and contrast–to-noise ratios than the steady state free precession sequence (SSFP) (n=30) but displayed a higher correlation with the MPS results, evaluated both qualitatively and quantitatively (II). The MRIAnxiety Questionnaire (MRI-AQ) was validated on patients, referred for MRI of either the spine (n=193) or the heart (n=54). The final instrument had 15 items divided in two factors regarding Anxiety and Relaxation. The instrument was found to have satisfactory psychometric properties (III). Patients who prior CMR viewed an information video scored significantly (lower) better in the factor Relaxation, than those who received standard information. Patients who underwent MPS scored lower on both factors, Anxiety and Relaxation. The extra video information had no effect on CMR image quality (IV).</p><p><strong>Conclusion:</strong> Single shot imaging in atrial fibrillation produced images with less artefact than a segmented sequence. In first-pass perfusion imaging, the sequence GRE-EPI was superior to SSFP. A questionnaire depicting anxiety during MRI showed that video information prior to imaging helped patients relax but did not result in an improvement in image quality.</p>
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