| 1. |
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| 2. |
- Andersson, Eva
(författare)
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Hörselscreening av en population med utvecklingsstörning : Utvärdering av psykoakustisk testmetod och av OAE-registrering som komplementär metod
- 2013
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Populationer med utvecklingsstörning behöver kontinuerlig hörseltestning, men konsensus om lämplig testmetod saknas.Syfte: Syftet med Studie I var att utvärdera psykoakustisk testmetod och med Studie II att utvärdera OAE-registrering som komplementär metod.Studie I. 1478 barn och vuxna med lätt till djup utvecklingsstörning, i åldrarna 7-91 år deltog i studien. De testades med tonaudiometri på sex frekvenser på screeningnivån 20 dB HL med lätt modifierad testutrustning. Kriterierna för remittering var tröskelnivåer på ≥ 25 dB HL på två frekvenser eller flera på ett öra eller båda. 1470 (99,5%) barn och vuxna medverkade i screeningen och 1325 (90%) testades på båda öronen på samtliga sex frekvenser. En majoritet, 987 (67,1%), medverkade i vanlig tonaudiometri, 234 (15,9%) i lekaudiometri, och 249 (16,9%) testades med observationsaudiometri. 669 (45%) visade normala värden medan 809 (55%) visade onormala värden relaterat till screeningkriterierna. Av de 809 accepterade 441 (54,5%) remittering för hörselutredning.Studie II. 38 vuxna med måttlig till djup utvecklingsstörning, i åldrarna 31-73 år deltog i studien, alla med ofullständiga testresultat vid tonaudiometri. Portabel utrustning, ILO 288 Echoport och dator Compaq LTE 5100 med mjukvara ILO 88 V 4.2, användes. Otoskopi och tympanometri kompletterade registreringen. Kriterierna för emissioner var S/N 3 dB eller mer och reproducerbarhet på 60% eller mer på åtminstone tre frekvensband. Kriterierna för partiella emissioner var desamma men för en eller två frekvenser. Två personer behövdes för att genomföra testningen: en för att hålla testpersonen lugn och tyst och den andra för att sköta testapparaturen. Reproducerbara TEOAE-svar registrerades från 11 öron (7 personer), partiella svar från 6 öron (4 personer), inga emissioner kunde registreras från 15 öron (10 personer) och 4 öron (4 personer) med otit eller vaxpropp testades inte. Registreringen från 24 öron (13 personer) kunde inte värderas p g a alltför mycket yttre och inre störningar. 8 personer vägrade delta i testningen. Endast 4 personer visade emissioner på båda öronen. Resultatet av undersökningen blev att 34 personer (89.5%) behövde testas om eller bli remitterade för ytterligare utredning, 21 av dem (55%) beroende på störningar vid registreringen eller p g a vägran att medverka.Konklusion: Tonaudiometri med lätt modifiering kan användas för screening av en population med lätt till djup utvecklingsstörning. TEOAE-registrering, som den genomfördes, kan inte uppfylla kraven på en fungerande testmetod för en population med måttlig till djup utvecklingsstörning. I det enskilda fallet kan TEOAE-registrering vara ett komplement till andra hörseltest. Det mest utmanande och tidskrävande är att introducera testprocedurerna på ett sätt som begränsar oro och skapar tillit. Oberoende av testmetod är en audionom med tålamod och vana att samarbeta med personer med utvecklingsstörning en viktig förutsättning för framgångsrik och säker testning.
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| 3. |
- Andin, Josefine, 1979-
(författare)
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Pharmacological and environmental modulations of the rat glutamatergic system
- 2006
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Glutamate is the principal excitatory neurotransmitter in the central nervous system and it is implicated in neural transmission, learning, memory processes and neuronal plasticity. In the glutamatergic synapse two main components are present; the glutamate receptors and the glutamate transporters. The receptors, the NMDA, AMPA, kainite and the metabotroptic receptors, are responsible for conveying neural transmission, including long term potentiation (LTP), synaptic strengthening and modification. The transporters, located to the neuronal membrane and to the membranes of surrounding astrocytes, regulates the extracellular concentration of glutamate and thereby the duration of the synaptic signal.Alterations in both receptor and transporter systems have been suggested to be important in the pathogenesis of several acute and chronic nervous system diseases, such as psychosis, mood disorders, epilepsy, Parkinson's disease and Alzheimer's disease. The pathophysiology of these disorders is not yet completely understood and the involvement of glutamate is unclear. In this thesis we have sought to investigate the role of the glutamatergic system in the treatment of mood disorders and dementia. The antidepressant drug amitriptyline exerts its main effects on the serotonergic and noradrenergic systems and the antidementia drug rivastigmine acts mainly on the cholinergic system. However, given the close relationship between different neurotransmitter systems we have investigated the influence of amitriptyline and rivastigmine on the mRNA expression of the neuronal transporter, EAAC1, in rats. The results showed for the first time an involvement of EAAC1 in amitriptyline and rivastigmine treatment. Amitriptyline induced an acute increase in EAAC1 mRNA expression, which 24 hour after administration returned to baseline levels. Chronic treatment, on the other hand, induces a significant decrease in cortical areas, which we suggest results in enhanced neuronal transmission. Rivastigmine treatment, acute as well as chronic, induced increases in the mRNA expression in hippocampus. We hypothesize that this counteracts the excitotoxic glutamate levels seen in Alzheimer's disease.Further, environmental enrichment has been shown to have beneficial effects on capillary supply, the number of glial cells and dendritic spines, the thickness and weight of cortex, the concentration of cholinesterase, LTP and synaptic strength in animals. It has also been reported that humans that lead an active life have a reduced risk of developing Alzheimer's disease. This suggests that an active and stimulated life may have a protective effect against dementia in man, by creating a cognitive reserve which provides a buffer against brain pathology or age-related changes. We investigated the influence of environmental enrichment on the mRNA expression of NMDA and AMPA receptors and on EAACl and showed for the first time that EAAC1 mRNA is decreased after environmental enrichment. This is probably followed by an increase of glutamate in the synapse, which in turn leads to enhanced neuronal transmission including enhanced memory formation and learning. Furthermore, we confirmed in greater detail previous findings on the upregulation of NMDA mRNA and show that the regulation is regionally and hemisphere specific. We also confirm that AMPA mRNA is not per se changed by environmental enrichment in adult animals.This work provides further evidence about the involvement of the glutamatergic system in affective and cognitive disorders. Improved knowledge of the glutamatergic system will contribute to the development of strategies aimed at limiting pathological changes associated with glutamatergic dysfunctions.
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| 4. |
- Angbratt, Marianne, 1947-
(författare)
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Estimated calcium intake related to lifestyle and bone mineral density in an adult Swedish population
- 2005
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Osteoporosis is a public health problem. It is a disease that is present for a long period without signs, before resulting in the clinical sign, i.e. fracture(s). Osteoporosis can be prevented in part and there are treatments. Among other lifestyle factors, the dietary intake of calcium is important when working with preventive intervention towards individuals and groups. For dietary assessment, an instrument adjusted for Swedish circumstances is needed.The aims of the thesis are to design and validate an instrument estimating calcium intake (I), to estimate calcium intake from dairy products and supplements in an adult Swedish population, and to explore associations between calcium intake and some lifestyle factors and between calcium intake and bone mineral density (II).Two questionnaires were prepared, one short (A), containing questions about dairy products and supplements, and another more extensive (B), with questions on a wide variety of food products. The questionnaires were validated with dietary history as the gold standard. Two age groups of women, 20-30 and 50-60 years, were included (n=467) (I). A randomised sample of 15% women and men aged 20-79 years in two communities answered a questionnaire (n= 1510). Forearm bone mineral density was measured in a subsample of this group (n=448) (II).We found questionnaire A to be sufficient when discriminating individuals with low calcium intake from individuals with sufficient calcium intake (I). The mean calcium intake from dairy products was well attained (878 mg/day) although the range was wide. However, 12% in the 20-30 years age group and 31% in the 70- 79 years age group did not meet the recommended daily intake. Associations were found between calcium intake and residence and also physical activity. There was a tendency towards an association between calcium intake and forearm bone mineral density. No other associations with lifestyle factors were observed (II).ln osteoporosis intervention work there is every reason to strive towards meeting the recommended daily intake for all individuals, and our quick and cheap food frequency questionnaire could be of value.
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| 5. |
- Anskär, Eva, 1957-
(författare)
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Time flies in primary care : a study on time utilisation and perceived psychosocial work environment
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Time utilisation among primary care professionals has been affected by structural changes and reorganisation performed in Swedish primary care over several decades. The work situation is complex with a heavy administrative work load. The overall aim with this thesis was to describe time utilisation among staff in Swedish primary care and to investigate associations with perceived psychosocial work environment and legitimacy of work tasks.Methods: A multicentre, descriptive, cross-sectional study design was used including all staff categories in primary care i.e. registered nurses, primary care physicians, care administrators, nurse assistants and allied professionals (physiotherapists, occupational therapists, psychologists, counsellors, dieticians and chiropodists) at eleven primary care centres located in southeast Sweden. The data collection consisted of a questionnaire including a subjective estimate of workload, the Bern Illegitimate Tasks Scale (BITS) and the Copenhagen Psychosocial Questionnaire (COPSOQ). Also, a time study was performed, where the participants reported their work time based on three main categories; direct patient work tasks, indirect patient work tasks and other work tasks, each with a number of subcategories. The participants reported time spent on different work tasks, day by day during two separate weeks. Response rates were 75% for the questionnaire and 79% for the time study.Results: In paper I the time study revealed that health professionals at the primary care centres spent 37% of their work time with direct patient work tasks. All professions estimated a higher proportion of time spent directly with patients than they reported in the time study. Physicians scored highest on the psychosocial scales of quantitative demands, stress and role conflicts. The proportion of administrative work tasks was associated with role conflicts, the more administration the more role conflicts. Findings in paper II were that more than a quarter of physicians scored above the cut-off value for BITS regarding unnecessary work tasks, which was significantly more than the proportion observed in all other professions in the survey. Across all staff groups, a perception of having to perform illegitimate work tasks was associated with experiencing negative psychosocial work environment and with high proportion of administrative-related work tasks.Conclusions: Swedish primary care staff spend a limited proportion of their work time directly with patients and primary care physicians perceive the psychosocial work environment in negative terms to a greater extent than all other staff members. Allocation of work tasks has an influence on the perceived psychosocial work environment. The perception of having a large number of illegitimate work tasks affects the psychosocial work environment negatively, which might influence the perception the staff have of their professional roles. Perception of high proportion of unreasonable work tasks is associated with a high proportion of non-patient-related administration.This thesis illuminates the importance of decision makers thoroughly considering the distribution and allocation of non-patient related work tasks among staff in primary care, in order to achieve efficient use of personnel resources and favourable working conditions. Hopefully, the results of this study will contribute to further development of primary care so that medical competence will benefit patients as much as possible.
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| 6. |
- Berg, Cecilia, 1976-
(författare)
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Mechanisms of platelet-mediated fibroblast proliferation
- 2003
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Wound healing is a multicomponent event that involves a network of molecular and cellular crosstalk between cells, including leukocytes, platelets and fibroblasts. Despite increased knowledge over the past decades regarding the regulation of cell and tissue growth, the inter- and intracellular systems that control wound healing are incompletely understood. The platelet is a rich source of growth factors essential to natural tissue repair. In the present thesis, the role of platelets and platelet-derived factors on fibroblast proliferation was evaluated, and related to the generation of reactive oxygen species (ROS) and eicosanoids.We found that whole platelets, platelet-derived growth factor (PDGF), transforming growth factor-ß (TGF-ß) and sphingosine-1-phosphate (S1P) induce fibroblast proliferation. Exposure of fibroblasts to these stimuli caused an extensive intracellular production of ROS, measured as increase in dichlorofluorescein fluorescence. Both fibroblast growth and the associated ROS production were inhibited by intracellular antioxidants (N-acetyl-L-cysteine (NAC) and pyrrolidinethiocarbamate (PDTC)) and NADPH-oxidase inhibitors (diphenyleneiodonium chloride (DPI) and apocynin). Moreover, platelet-mediated fibroblast proliferation was abrogated in the presence of the sphingosine kinase inhibitor DL-threo-dihydrosphingosine, but only slightly affected by antibodies directed against PDGF and TGF-ß.The production of the arachidonic acid metabolite 5-hydroxyeicosatetraenoic acid (5-HETE) in fibroblasts, analysed by HPLC, was markedly elevated in the presence of platelets. Furthermore, inhibition of phospholipase A2, by 7,7-dimethyl-5,8-eicosadienoic acid (DMDA), or 5-lipoxygenase, by 5,8,11-eicosatriynoic acid (ETI) or 5,6-dehydro arachidonic acid (5,6-dAA), decreased the platelet-induced fibroblast proliferation and formation of 5-HETE. This indicate a role for transcellular metabolism of arachidonic acid during platelet-fibroblast interaction.We conclude that the production of ROS and 5-HETE is crucial in the plateletmediated stimulation of fibroblast growth. These findings may represent new targets in the future therapy for a successful wound healing.
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| 7. |
- Berg, Katarina, 1959-
(författare)
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Postoperative recovery in daysurgery : Evaluation of psychometric properties and clinical usefulness of a questionnaire in day surgery
- 2010
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Day surgery has increased during recent decades in many countries and represents approximately 50% of surgical procedures performed in Sweden. Day surgery implies that the patient is admitted and operated on during the same day and discharged without an overnight stay at the surgery unit. Undergoing a day surgical procedure thereby means that the major part of the postoperative recovery takes place in the patient’s home, leaving the patient and his/her supportive network responsible for the postoperative care. Day surgery also implies that health care professionals have to adapt to outpatient care and find valid measurements for monitoring a patient’s recovery progress after discharge.Aims: The aim of Study I was to evaluate the psychometric properties of a translated version of the Post-discharge Surgical Recovery (PSR) scale in a Swedish day surgery sample in terms of data quality, internal consistency, dimensionality and responsiveness. The aim of Study II was to describe postoperative recovery on postoperative days 1, 7 and 14 after different orthopaedic day surgical procedures, as well as to identify possible predictors associated with postoperative recovery two weeks after surgery.Methods: Six-hundred and seven patients who had undergone an orthopaedic surgical procedure (n=358), general surgery (n=182) or gynaecological surgery (n=67) were included. To assess postoperative recovery, the PSR scale and the emotional state, physical comfort and physical independency dimensions of the Quality of Recovery-23 (QoR-23) were used. In addition, patients’ background data and self ratings of their ability to work or handle usual business and general health were obtained. Data were collected preoperatively and on postoperative days 1, 7 and 14. In Study I data quality and internal consistency were evaluated using descriptive statistics, correlation analyses and Cronbach’s alpha. The dimensionality was determined using an exploratory factor analysis, and the responsiveness was evaluated through the standardized response mean (SRM) and the area under the receiver operating characteristics curve (AUC). In Study II, patients’ postoperative recovery and general health were compared over time using Friedmann’s ANOVA and between surgical groups of patients using the Kruskal-Wallis test. To determine predictors of recovery, a multiple linear regression analysis was performed with the PSR score on postoperative day 14 as the dependent variable.Results: In Study I, two items were deleted from the Swedish version of the PSR scale. This was based on several low inter-item (<0.30) and item-total correlations (<0.40) and substantial ceiling effects (65%). After the deletion of two items, the Cronbach’s coefficient alpha was 0.90 and the average interitem correlation was 0.44. According to the factor analysis, a single dimension was found explaining the common variance to 44%. The SRM (1.14) indicated a robust ability to detect changes in recovery. The AUC was 0.60 for the entire scale, but varied (0.58-0.81) when the PSR score on postoperative day 1 was categorized into three intervals. In Study II, the shoulder patients experienced significantly lower postoperative recovery and general health one and two weeks after surgery (p<0.001). Significant predictors of recovery on postoperative day 14 were age, perceived health and emotional status on postoperative day 1 and type of surgery, and explained the dependent variable to 33%.Conclusions: The Swedish version of the PSR scale seems to be a consistent and valid instrument for the assessment of postoperative recovery at home in Sweden. The recovery process for orthopaedic day surgery patients differs, with shoulder surgery patients in particular showing poor recovery, which could be considered when day surgery patient education programmes are developed.
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| 8. |
- Bergstrand, Sara, 1978-
(författare)
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Tissue Blood Flow Responses to External Pressure Using LDF and PPG : Testing a System Developed for Pressure Ulcer Research
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Pressure ulcers are a problem for immobile individuals, and having pressure ulcers impact and restrict the daily and are often associated with pain. Pressure ulcers occur frequently and cause high costs for the health care system. The prevention of pressure ulcers by focussing on different mattresses and overlays aimed to reduce the interface pressure or the pressure exposure of the tissue. The problem is the poor evaluation of this type of equipment. There are important factors regarding pressure ulcer development, pressure, shear, temperature and humidity. People are affected by external pressure in different ways and therefore it is preferable to measure the effect of pressure as a complement to the pressure measurement and thus we consider blood flow measurements to be a suitable method.Aims: The aim of Study I, the first part in this thesis was to investigate the existence of sacral tissue blood flow at different depths in response to external pressure in elderly individuals as a part of evaluation of a. newly developed system. The aim of Study II, the second part was to evaluate a multiparametric system combining LDF and photoplethysmography into a single probe, for the simultaneous measurement of blood flow at different depths in the sacral tissue when the tissue is exposed to external load. This new system will be used to facilitate the understanding of pressure ulcer formation.Methods: To be able to observe tissue blood flow, the non-invasive optical methods laser Doppler flowmetry and photoplethysmography were used. In this thesis a newly developed prototype probe was used, combining the two methods. Green light and infrared light were used in the PPG instrument for penetrating the depths of approximately 2 mm, 8 mm and 20 mm depths. A HeNe laser was used to measure the superficial skin blood flow, <1 mm depth. The prototype probe, made of silicone was fixed in a stiff 10×10 cm plate.Seventeen active individuals over the age of 60 were recruited for the two studies. In Study I, the subject´s sacral blood flow and tissue thickness (using ultrasound) were measured in unloaded position and in supine position loading the area with their own body weight. In Study II, the sacral area was provoked with external load at 37.5 mmHg and 50.0 mmHg and the relative change in blood flow at different depths was observed before, during and after load.Results: Study I showed that the sacral tissue in elderly individuals is highly affected by load and is compressed by 60.3 ± 11.9%. The mean sacral tissue thickness was 26 ± 13 mm in unloaded tissue and 10 ± 6 mm in loaded tissue. Correlations were found between BMI and tissue thickness: both TTunload r=0.68 (p=0.003) and TTload r=0.68 (p=0.003). Almost all subjects had affected blood flow superficially but only occasionally deeper in the tissue and findings may indicate that the blood flow is occluded in the superficial layer before it is occluded deeper in the tissue structure. The most common response in Study II was an increase in blood flow while loading. In those occasions when the blood flow decreased, it was mostly affected at the skin surface and the reactive hyperaemia occurred more frequently in the superficial tissue structures. The blood flow responses may be different in the different tissue layers.Conclusions: The newly developed system was found to be suitable for measuring tissue blood flow at different depths; however the prototype probe had some limitations that will be solved in the further development of the system into a thin flexible probe with ability to measure a larger area.
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| 9. |
- Blomqvist, Henrik, 1975-
(författare)
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Monocyte chemoattractant protein-1 and CC-chemokine receptor-2 in two different conditions related to atherosclerosis
- 2004
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atherosclerosis is the leading cause of death in the industrialized parts of the world. The pathological process is characterised by increased lipid influx to the arterial wall due to elevated circulating levels of low density lipoprotein (LDL). LDL is oxidatively modified by reactive oxygen species forming oxLDL. OxLDL is highly proinflammatory and is initiating an inflammatory response in the artery by up-regulation of proinflammatory signals e.g. Monocyte chemoattractant protein-1 (MCP-1). MCP-1 is promoting monocyte arrest on the endothelium and subsequent transmigration to the intima. MCP-1 is acting through the CC-chemokine receptor-2 (CCR2) on monocytes. MCP-1 and CCR2 are playing key-roles in atherogenesis through their effect on monocyte recruitment. In this thesis MCP-1 and CCR2 were studied in two clinically different conditions related to atherosclerosis - isolated asymptomatic hypercholesterolaemia and diagnosed coronary artery disease (CAD). We wanted to study the possible differences of proatherogenic patterns in clinical conditions that are at opposite ends in the clinical spectrum of atherosclerosis.In paper I, we studied if plasma levels of MCP-1 and the gene expression of CCR-2 were elevated above normal in subjects with asymptomatic, isolated hypercholesterolaemia and if statin treatment could influence plasma levels of MCP-1 and other inflammatory markers. In paper ll we studied the same parameters but in patients with diagnosed CAD as stable angina pectoris and acute coronary syndrome. In neither study we could see any differences regarding MCP-1 or CCR2 between patients and controls. However, in the CAD patients we could see an increased inflammatory activity as elevated levels of CRP. This inflammatory activity was not reflected on any other of the inflammatory markers analysed. In conclusion, the results from this thesis do not support the idea of circulating MCP-1 and CCR2 gene expression on circulating monocytes as clinical markers of atherosclerosis in these patient categories.
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| 10. |
- Clifford, Jenny, 1980-
(författare)
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Gold allergy : In vitro studies using peripheralblood mononuclear cells
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Positive patch test reactions to gold are commonly seen in dermatology clinics, but it is veryunusual for the patients to actually have any clinical symptoms. It is also common with irritantreactions that are not linked to adaptive immunity. Therefore, a deeper understanding of themechanisms underlying allergic contact dermatitis (ACD) reaction, and the search for acomplementing diagnostic tool, is important.In paper I we included three subject groups; one with morphologically positive patch testreactions to gold sodium thiosulphate (GSTS, the gold salt used in patch testing), one withnegative patch tests, and one with irritant reactions to gold. Blood samples were collected andexamined regarding the proliferation rate and which cytokines were secreted after culturingwith GSTS. We saw that the cultured lymphocytes from the allergic donors proliferated at asignificantly higher rate than the two other subject groups, and that the cells secreted cytokinesof both Th1 (Interferon (IFN) -g and Interleukin (IL) -2) and Th2 (IL-13 and IL-10) types. Theallergic donors secreted significantly higher levels of IFN-g, IL-2 and IL-13 than the two othersubject groups. Both the negative and irritant subject groups showed suppressed levels of thecytokines as compared with the unstimulated cultures, demonstrating the immunosuppressingeffects of gold.We also examined whether any of the analyzed markers, alone or combined, could be usedas an aid for diagnosing ACD to gold. We found that the IFN-g assay yielded the highestsensitivity (81.8 %) and specificity (82.1 %), and also identified 87.5 % of the irritant group asnon-allergic.In paper II we decided to investigate what cell types and subsets that reacted to the goldstimulation. We analyzed proliferation rate and expression of CD45RA, CD45R0, cutaneouslymphocyte-associated antigen (CLA) and the chemokine receptors CXCR3, CCR4 andCCR10. Similar to what has previously been published about nickel (Ni) allergy, the cells fromthe gold-allergic subjects that reacted to the GSTS stimulation expressedCD3+CD4+CD45R0+CLA+. However, contrary to findings in studies on Ni-reactive cells, wesaw no differences between allergic and non-allergic subjects regarding any of the chemokine receptors studied.In conclusion, we found that analysis of IFN-g might be a useful complement to patchtesting, possibly of interest in avoiding the need for repeated tests to rule out irritant reactions.We also saw that the cells that proliferated in response to gold were memory T-cells expressingCD4 and CLA, the marker for skin-homing. However, these cells did not express elevatedlevels of any of the chemokine receptors analyzed, showing that there are both similarities anddifferences between the mechanisms for Ni allergy and gold allergy.
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| 11. |
- Dahlfors, Gunilla
(författare)
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Growth factors and their interaction in the regulation of vascular cells : with special reference to diabetes
- 1999
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Proliferation of vascular smooth muscle cells plays an important role in the development of atherosclerosis and in restenosis following balloon angioplasty. This study focuses on growth factors associated with diabetic vascular disease and their interaction in the regulation of vascular smooth muscle cell growth.The effect of streptozotocin-induced diabetes on proliferation of cells in aortic media two days after balloon angioplasty was studied. All proliferating cells in the aortic media were smooth muscle cells. In diabetic rats, the amount of proliferating cells was lower than in control rats. This was not accompanied by a change of transforming growth factor-ß1 (TGF-ß1) gene expression. Total TGF-ß1 levels in serum of diabetic rats was slightly lower and might possibly contribute to the inhibited proliferation of smooth muscle cells.The effect of angiotensin II on platelet-derived growth factor-BB(PDGF-BB)-induced growth was studied in cultured rat vascular smoothmuscle cells. Angiotensin II, acting through the AT1 receptor, transientlyinhibited the growth effect of PDGF-BB for approximately 6 hours. Thiswas not due to an autocrine effect of TGF-ß1, a growth factor consideredto mediate growth inhibitory actions of angiotensin II. Inhibition wasneither due to inhibition of PDGF-ß receptor phosphorylation.Large vessel endothelial cells from bovine aorta were shown to express and secrete insulin-like growth factor binding proteins (IGFBPs). Vascular endothelial growth factor (VEGF) and TGF-ß1, both associated with diabetic vascular complications, modulated the expression of IGFBPs in a way that might suggest increased bioavailability of insulin-like growth factor-I (IGF-I) locally in the vessel wall. VEGF, which is highly specific for endothelial cells, and TGF-ß1, might in this way indirectly regulate smooth muscle cell growth.In conclusion, we have shown that experimental diabetes has an inhibitory effect on smooth muscle cell proliferation in vivo, that interaction of growth factors, as shown for angiotensin II and PDGF-BB, might be of great importance for regulation of smooth muscle cell growth and that VEGF and TGF-ß1 regulate the IGF-system in large vessel endothelial cells with possible implications for regulation of smooth muscle cell function.
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| 12. |
- Dahlqvist Leinhard, Olof, 1978-
(författare)
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Quantitative magnetic resonance in diffuse liver and neurological disease
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Magnetic resonance (MR) has become one of the most important diagnostic tools in modern medicine. It provides superior soft tissue contrast compared to other imaging modalities, it is extremely flexible as it can be used to image all parts of the body, and it is considered to be safe for patients.Today almost all MR is performed in a non-quantitative manner, only by comparing neighbouring tissue in the search for pathology. It is possible to quantify the MR-signals to its physical entities, but time consuming and complicated calibration procedures have prevented this in clinical routine.In this work two different applications of quantitative MR-spectroscopy in diffuse liver and neurological disease, and a new rapid method for simultaneous quantification of proton density, T1 relaxation and T2* relaxation in MR-imaging are presented.In Paper I, absolutely quantified phosphorus MR-spectroscopy was tested as a predictive tool in order to determine the degree of fibrosis on patients with diffuse liver disease. One group with steatosis and none to moderate inflammation (n=13), one group with severe fibrosis or cirrhosis (n=16), and one group of healthy volunteers (n=13) were included in the study.Lower concentrations of PDE (p = 0.025), and a higher metabolic charge (AC) [42] (p < 0.001) were found in the cirrhosis group. A sensitivity and specificity of 81% and 69% respectively, were found for the discrimination between mild and advanced fibrosis using PDE concentrations, and 93% and 54% using AC. The results suggest PDE as a marker of liver fibrosis and AC as a potential clinically useful parameter in discriminating mild from advanced fibrosis.In Paper II proton MR-spectroscopy was used to investigate if there were differences in the concentrations of the observable metabolites in normal appearing white matter in patients with clinically definite multiple sclerosis (MS), and with normal MR-images compared to healthy volunteers. This 'MRI-negative' group consisted of fourteen patients which were compared with fourteen healthy controls. Absolutely quantified proton MR-spectra were acquired from four different voxels in NAWM.Significant differences in absolute metabolite concentrations were observed between the two groups. The MS-patients had lower total N-acetyl compounds (tNA) (p=0.002) compared to the healthy controls and lower concentration of choline-containing compounds (Cho) compared to the healthy controls (p<0.001). EDSS showed a slightly positive correlation to myolns concentrations (0.14mM/EDSS,r2 = 0.06) and a slightly negative correlation to tNA concentrations (-0.41 mM/EDSS,r2 = 0.22). The finding of lower Cho concentrations has not been reported previously and was unexpected.In Paper III a new rapid imaging method was presented for determination of proton density, B1, T2* relaxation and T1 relaxation. The method was based on a modified Look-Locker pulse sequence with two main differences. (1) The exchange of the inversion pulse in the Lock-Looker sequence to a saturation pulse in order to enable detection of the B1 field, and (2) the introduction of a multi-echo read-out to enable the detection of T2*. The signal intensity was then scaled to proton density using the estimated B1, T1, and T2* value.The method was validated in vitro, using phantoms filled with solution of different T1 and T2* water relaxation values, and by comparing the results of the measurements to reference metcyods. In vivo the method was compared with literature values.The validation showed that the method was highly accurate, both in vitro and in vivo, and that this method enabled quantitative imaging of MR-parameters within a clinically feasible examination time. Potential applications of the method are, among a great range of possibilities, to rapidly provide all the necessary quantification parameters in MR-spectroscopy, and to simultaneously provide fast quantitative diagnostic imaging.
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| 13. |
- Dahlström, Nils, 1969-
(författare)
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Magnetic Resonance Imaging of the Hepatobiliary System Using Hepatocyte-Specific Contrast Media
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There are two Gadolinium-based liver-specific contrast media for Magnetic Resonance Imaging on the market, Gd-BOPTA (MultiHance®, Bracco Imaging, Milan, Italy) and Gd-EOB-DTPA (Primovist®, Bayer Schering Pharma, Berlin, Germany). The aim of this study in two parts was to evaluate the dynamics of biliary, parenchymal and vascular enhancement using these contrast media in healthy subjects. Ten healthy volunteers were examined in a 1.5 T magnetic resonance system using three-dimensional Volumetric Interpolated Breath-Hold (VIBE) sequences for dynamic imaging with both contrast media – at two different occasions – until five hours after injection. The doses given were 0.025 mmol/kg for Gd-EOB-DTPA and 0.1 mmol/kg for Gd-BOPTA. The enhancement over time of the common biliary duct in contrast to the liver parenchyma was analyzed in the first study. This was followed by a study of the image contrasts of the hepatic artery, portal vein and middle hepatic vein versus the liver parenchyma.While Gd-EOB-DTPA gave an earlier and more prolonged enhancement of the biliary duct, Gd-BOPTA achieved higher image contrast for all vessels studied, during the arterial and portal venous phases. There was no significant difference in the maximal enhancement obtained in the liver parenchyma.At the obtained time-points and at the dosage used, the high contrast between the common biliary duct and liver parenchyma had an earlier onset and longer duration for Gd-EOB-DTPA, while Gd-BOPTA achieved higher maximal enhancement of the hepatic artery, portal vein and middle hepatic vein than Gd-EOB-DTPA. Diseases of the liver and biliary system may affect the vasculature, parenchyma, biliary excretion or a combination of these. The clinical context regarding the relative importance of vascular, hepatic parenchymal and biliary processes should determine the choice of contrast media for each patient and examination.
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| 14. |
- Daremo, Åsa, 1961-
(författare)
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Participation in occupational therapy in psychiatric care
- 2010
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- One of the most important challenges of health and medical care is to strength the role of the patient in the treatment. In psychiatric care the patient must be seen as a resource and should be given the opportunity to participate in his treatment. The overall aim of the thesis was to investigate and describe how patients in psychiatric care perceive participation, and how existing assessments support participation.Study I describes how patients in psychiatric institutional care perceived their opportunities to be active and to participate in their own treatment. The ICF (International Classification of Functioning Disability and Health) inspired the study. By means of a questionnaire, 61 patients reported their opinions of the value of received care, highlighting concepts such as activity and participation. Ten of those patients were then selected for a semi-structured interview. The study showed that patients who were treated according to compulsory care (LPT) were generally more dissatisfied with their opportunities to be active and participate in their own care than patients treated according to the law of health and medical care (HSL). Younger patients in particular were more dissatisfied. Some important factors in the environment were continuity and reception from the staff. Facilitating factors for activity and participation were agreement between patient and staff about the treatment plan, discussions about expectations, and creating conditions for engagement in activities and or responsibility.Study II investigates if there is harmony between the CPRS-S-A (Comprehensive Psychopathological Rating Scale-Self-Assessment), the OCAIRS–S (Occupational Circumstances Interview and Rating Scale) and the OSA (Occupational Self Assessment), and if they can replace each other when the occupational therapist collects information about the patient. Another aim was to investigate how occupational therapist uses the collected information in the treatment plan process. Fourteen patients with depression disorders took part in the study. The study showed that even if the symptoms of the disease were improved at the end of the treatment period the patients still had problems with occupational performance, reduced self-confidence and the structure of their day. Consequently the assessments cannot replace each other. The study emphasized the importance of using both interview and self-assessments when collecting information about the patient, since these methods complement each other in identifying the needs and goals of the treatment. Many problems were related to the patient’s social environment but this was not reflected in the treatment plan; few goals were identified in this area.In conclusion, occupational therapists should use self-assessments and interviews in order to support the patient’s participation in psychiatric care. Furthermore, it is important to use assessments for both occupational performance and medical symptoms when identifying the patient’s needs and goals of treatment since there is a discrepancy between the two areas; symptoms are reduced earlier than perceived problems in occupational performance. Regardless of what kind of law the patient is treated under, all patients have the right to participate in their own treatment. This thesis also shows that the social environment is important in enabling the participation of patients in their psychiatric care.
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| 15. |
- Davidson Söderman, Kristina, 1958-
(författare)
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Hospital admissions in Greece and Sweden : a comparative study of two communities
- 2002
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis reports comparative studies of admissions to regional hospitals in two communities, one in Greece and one in Sweden, during a two-year period, 1986-1987. The comparison was made using care episode diagnoses coded in the International Classification of Diseases, ICD 9. All cases hospitalised during this period were distributed by age, sex, residence and diagnoses.The results indicate that even if there were cultural and socio-economic differences between the two areas, there were also important similarities in the hospitalisation patterns. The hospitalisations seemed to be more equally distributed between the sexes and between urban and rural areas in Sweden than in Greece, where it appeared that the rural population, and women in particular, did not get hospital care according to their needs. It was also found that study of hospital admission is associated with methodological difficulties because the use of hospital services is a complex phenomenon. The thesis includes discussions about the variety of factors that can have influenced the results.
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| 16. |
- Dekker Nitert, Marloes, 1976-
(författare)
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IGF-I receptors, insulin receptors and insulin/IGF-I hybrid receptors in human endothelial cells : with special reference to diabetes
- 2005
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients with diabetes mellitus are known to develop vascular complications, which occur as macroangiopathy, atherosclerosis and mediasclerosis, as well as microangiopathy, e.g. retinopathy and nephropathy. The precise mechanisms causing these complications have not yet been elucidated. The microvascular complications are closely associated with the glycaemic control, which also is a risk factor for the diabetic macroangiopathy. The possible roles of insulin and the related peptide IGF-I, whose levels are affected by diabetes mellitus, are not clear. This study aims to characterise the presence and function of insulin and IGF-I receptors in human endothelial cells.Two types of human endothelial cells were studied; human umbilical vein endothelial cells (HUVEC) and human coronary artery endothelial cells (HCAEC). The presence of insulin receptors and IGF-I receptors was studied at mRNA level by real-time PCR and at protein level by ligand binding and by Western blot analysis after immunoprecipitation. Receptor activation was determined as tyrosine phosphorylation.Both HUVEC and HCAEC were found to express IGF-I receptors and insulin receptors at mRNA and protein levels. The amount of IGF-I receptor mRNA exceeded insulin receptor mRNA by 3.5 and 14-fold in HUVEC and HCAEC, respectively. In HUVEC, the higher expression of IGF-I receptor mRNA compared to insulin receptor mRNA was present in both freshly isolated and cultured cells. Ligand binding studies showed a higher specific binding of 125I-IGF-I than of 125I-insulin which also suggest the presence of more IGF-I receptors than insulin receptors. In HUVEC, the specific binding was 0.64 ± 0.25% (mean ± SEM) for 125I-IGF-I and 0.25 ± 0.092% for 125I-insulin. The EC50 for 125I-IGF-I displacement was 3.6 x 10-10 M for IGF-I vs. 8.25 x 10-8 M for insulin. The EC50 for 125I-insulin displacement was 2.6 x 10-10 M for insulin and 7.39 x 10-9 M for IGF-I. In HCAEC, the specific binding was 1.37 ± 0.09% and for insulin 0.17 ± 0.03%. The EC50 value for IGF-I displacement were 6.9 X 10-10 M for IGF-I, 8.7 X 10-6 M for insulin and 7.5 X 10-8 M for the insulin analogue glargine. Due to the very low specific binding of 125I-insulin, it was not possible to calculate the concentration needed to give half-maximal displacement, EC50, of 125I-labelled insulin. Both cell types expressed insulin/IGF-I hybrid receptors. Receptor phosphorylation studies showed that IGF-I receptor could be activated by 10-10 to 10-8 M IGF-I in both cell types. Insulin receptors were activated by 10-9 to 10-8 M insulin in HUVEC and HCAEC. IGF-I was able to activate insulin receptor phosphorylation at low concentrations, 10-9 to 10-8 M, which also is an indication of the presence of hybrid receptors.In conclusion, two types of human endothelial cells, HUVEC and HCAEC, express more IGF-I receptors than insulin receptors, and they also express insulin/IGF-I hybrid receptors. IGF-I and insulin were found to phosphorylate their own receptor while IGF-I also seemed to be able to phosphorylate hybrid receptors. The results suggest an important role of the IGF-I receptor in human endothelial cells.
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| 17. |
- Djerf, Emelie, 1980-
(författare)
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Studies on the effect of ErbB tyrosine kinase inhibitors on malignant melanoma growth and survival in vitro
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Malignant melanoma has one of the fastest increasing incidences among the different types of cancerin the Western world. This raise can partly be ascribed to the change in sun habits that has takenplace during the last decades, since the major external risk factor for melanoma is exposure toultraviolet radiation. Patients with early stages of melanoma can often be cured by surgery, howeverfor patients suffering from metastatic melanoma there are only a few treatment options available.Unfortunately malignant melanoma is often resistant to radio-, bio- and chemotherapy and treatmentwith the currently most frequently used agent, dacarbazine, is characterized by a very low clinicalresponse rate. Therefore, there is an urgent need for new treatment strategies which can increase theoverall survival and cause less severe side effects.The aim of this thesis was to investigate the anti-tumor effect of two different tyrosine kinaseinhibitors (TKIs), gefitinib and canertinib, on two different human malignant melanoma (RaH3 andRaH5) cell lines. We investigate the effect of these two drugs on cell proliferation and survival andstudied the effect of gefitinib and canertinib on ErbB1-4 receptor phosphorylation, as well as Akt,Erk1/2 and Stat3 activity.Our results showed that phosphorylation of ErbB1, ErbB2 and ErbB3 decreased followingtreatment with both gefitinib and canertinib and that the subsequent downstream signaling via Akt,Erk1/2 and Stat3 was inhibited after TKI treatment. However, it was noted that the gefitinibinducedinhibition of Akt, and particularly Erk1/2, was transient and only a weak inhibition of Stat3phosphorylation was seen. Gefitinib treatment of the RaH3 and RaH5 cells resulted in anaccumulation of the cells in the G1 phase of the cell cycle without any induction of apoptosis.Canertinib caused a more pronounced inhibition of Akt, Erk1/2, and Stat3 phosphorylation thangefitinib. This might be one explanation to why canertinib induced apoptosis in RaH3 and RaH5cells whereas gefitinib only caused cell cycle arrest. In conclusion, gefitinib and canertinib displaypromising anti-tumor effects on ErbB expressing malignant melanoma and might be used in futurestudies in combination with conventional chemotherapy or other targeted therapies in the treatmentof malignant melanoma.
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| 18. |
- Erichsén, Eva, 1959-
(författare)
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Constipation in palliative care : Prevalence, definitions, symptom distress and risk-factors
- 2015
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Constipation for patients in palliative care is common and described with variations in prevalence. Side -effects from opioid- treatment, is considered to be one of the main factors leading to constipation. The overall aim of the thesis was to study constipation among patients admitted to specialized palliative care- settings in Sweden. The specific aims of the thesis were 1) To describe and explore the prevalence, definition and symptom distress of constipation by applying different definitions of constipation, in patients admitted to specialized palliative care settings in Sweden. 2) To identify factors related to constipation in patients in specialized palliative care and comparing these factors for patients with different types of constipation to patients without constipation.Methods: A literature- search were conducted where prevalence of- and factors related to constipation was explored and included in a questionnaire, developed for this thesis. Data was collected in a cross- sectional design with a response rate of 50% and analysed with logistic regression.Results: A total of 485 patients from 38 specialized palliative care- units in Sweden participated. Prevalence of constipation for patients in specialized palliative care varied between 7- 43 % depending on definition used. Two different constipation- groups were identified: Medical constipation- group 23% (MCG) and Perceived constipation- group 35% (PCG). Three sub- groups was also identified: patients with i) only ≤ 3 defecations/week, 7%, ii) only perception of being constipated, 19%, and iii) patients with both ≤ 3 defecations/ week and perception of being constipated,16%. Several factors were found to be related to constipation as hospitalisation, absence of laxative- treatment, haemorrhoids, poor appetite, hard stool form and opioids.Conclusions: Prevalence of constipation may differ depending on definitions used. Distress from constipation and other factors related to constipation, than opioids, needs to be incorporated into the clinical constipation- assessment. Validated constipation assessment tool needs to be developed.
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| 19. |
- Eriksson, Therese, 1979-
(författare)
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Organelle movement in melanophores: Effects of Panax ginseng, ginsenosides and quercetin
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Panax ginseng is a traditional herb that has been used for over 2000 years to promote health and longevity. Active components of ginseng include ginsenosides, polysaccharides, flavonoids, polyacetylenes, peptides, vitamins, phenols and enzymes, of which the ginsenosides are considered to be the major bioactive constituents. Although widely used, the exact mechanisms of ginseng and its compounds remain unclear. In this thesis we use melanophores from Xenopus laevis to investigate the effects of Panax ginseng extract G115 and its constituents on organelle transport and signalling. Due to coordinated bidirectional movement of their pigmented granules (melanosomes), in response to defined chemical signals, melanophores are capable of fast colour changes and provide a great model for the study of intracellular transport. The movement is regulated by alterations in cyclic adenosine 3’:5’-monophosphate (cAMP) concentration, where a high or low level induce anterograde (dispersion) or retrograde (aggregation) transport respectively, resulting in a dark or light cell. Here we demonstrate that Panax ginseng and its constituents ginsenoside Rc and Rd and flavonoid quercetin induce a concentration-dependent anterograde transport of melanosomes. The effect of ginseng is shown to be independent of cAMP changes and protein kinase A activation. Upon incubation of melanophores with a combination of Rc or Rd and quercetin, a synergistic increase in anterograde movement was seen, indicating cooperation between the ginsenoside and flavonoid parts of ginseng. Protein kinase C (PKC) inhibitor Myristoylated EGF-R Fragment 651-658 decreased the anterograde movement stimulated by ginseng and ginsenoside Rc and Rd. Moreover, ginseng, but not ginsenosides or quercetin, stimulated an activation of 44/42-mitogen activated protein kinase (MAPK), previously shown to be involved in both aggregation and dispersion of melanosomes. PKC-inhibition did not affect the MAPK-activation, suggesting a role for PKC in the ginseng- and ginsenoside-induced dispersion but not as an upstream activator of MAPK.
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| 20. |
- Evertsson, Sofia, 1972-
(författare)
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Significance of molecular genetic alterations and apoptosis in colorectal cancer
- 2002
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal cancer is a serious health problem in Western societies. In Sweden it is the second most common malignancy among females, and the third in males, and the third leading cause of cancer related death in both sexes. To date it is known that several biological pathways can lead to colorectal cancer. An enhanced understanding of the molecular and cellular events occurring within these pathways should ultimately result in better tailored preventive, diagnostic and therapeutic approaches. An important goal is to identify cancer predisposing genetic variants that would make genetic screening of at-risk individuals possible, and to find parametres which could define homogenous subgroups associated with a certain prognosis.Impaired apoptotic processes have been implicated in colorectal tumourigenesis. In order to explore the significance of apoptosis in relation to proliferative activity, and other clinicopatological data including prognosis, apoptotic rates were measured by TUNEL in 158 colorectal tumours. A significant increase of apoptotic rate was observed with advancing tumour stage, from Dukes' A to D. Apoptotic rates were further significantly associated with the proliferative activity in the tumour, indicated by the proliferating cell nuclear antigen (PCNA). Thus it seems that apoptotic levels in the tumour might reflect tumour progression, and further that the processes of apoptosis and proliferation are coupled. Apoptosis was not related to p53, bcl-2 or K-ras, and did not confer any additional prognostic information.APC has been referred to as a "gatekeeper" in the progression of colorectal cancer. It is in a key position to regulate the balance between cell adhesion and migration and may also be involved in proliferation and apoptosis. The two germ line APC variants I1307K and E1317Q have been associated with increased colorectal cancer risk in certain populations, but have yet never been investigated in Swedish colorectal cancer patients. We screened J 94 colorectal cancer patients with and without a family history of colorectal cancer by DNA sequencing analysis, but did not find any of the variants. We conclude that I1307K and E1317Q are rare or absent in this population and should not confer any increased colorectal cancer risk in the Swedish population.The microsatellite instability pathway accounts for the majority of tumours in hereditary non-polyposis colorectal cancer (HNPCC) patients and about 15% of sporadic colorectal cancer cases. Inactivated mismatch repair (MMR) genes leads to an increased mutation rate, especially within repetitive DNA sequencies called microsatellites which are prone to replication errors, a phenomenon referred to as microsatellite instability (MSI). Several genes with microsatellites within their coding regions are targeted by MSI, and are possibly involved in tumourigenesis, including the repair gene MBD4 which is involved in maintaining the integrity of genomic methylation patterns. We aimed to determine the microsatellite status of 201 colorectal tumours using the marker Bat 26 in order to evaluate the relationship of MSI and clinicopathological variables including survival. We further aimed to investigate whether MBD4 is a MSI target gene in colorectal cancer, and to search for mutational associations with clinicopathological factors to reveal eventual phenotypical effects. Surprisingly, MSI was not associated with survival, as opposed to many previous studies, suggesting that the prognostic significance and the factors associated with it demands further investigation. MBD4 seemed to be a target of MSI, since the mutations were restricted only to MSI tumours. The clinicopathological variables associated with the MBD4 mutated tumours were likely the reflection of MSI features aquired prior to the MBD4 mutation, including right colon location and mucinous histology. The significance of these mutations remains to be determined in a largermaterial.
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| 21. |
- Flankegård, Gunilla, 1974-
(författare)
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Childhood functional constipation : Parents' everyday life experiences
- 2022
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Functional constipation is the most common chronic disorder in childhood with a great impact on family life. Treatment focuses on the behavioural nature of the disorder with toilet training and laxatives, with the goal of daily stool passage without difficulties. Management of care is predominantly carried out at home by parents, making them key partners in the paediatric care.Aim: The overall aim of this thesis was to explore and understand childhood functional constipation through the experiences of parents.Design and method: This thesis comprise two studies based on a phenomenological research method and design with an inductive reflective lifeworld approach using qualitative individual interviews to gather data. A theoretical framework was used in the analysis to further elucidate the findings.Findings: Shame was the essential finding, providing the reason parents acted in certain ways and the result of the same actions. Study I showed that everyday life was put on hold due to the time and effort invested in the adaptations demanded by the constipation. This left the parents feeling lonely, guilty, and fighting frustrating battles as they tried to gain control by being always one step ahead. Study II showed that giving constipation treatment resulted in parents questioning their parental identity. Treatment needed to be affirmed, as doubt and second thoughts sometimes made parents give treatment against their own will as well as defying their child’s will, bordering on feelings of being abusive. The findings were interpreted in the light of theories of illness beliefs and good parenting beliefs, suggesting belief systems are the path into the parents’ feelings of shame. Re-evaluating the beliefs might diminish failure to adhere to treatment regimens.Conclusions: This project shows that functional constipation is like other childhood chronic illnesses in respect of its importance and impact on everyday family life. Shame is a prominent feature of functional constipation experiences. However, the shame felt might be mitigated by targeting and re-evaluating the belief systems that form the lifeworld of the parents and family.
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| 22. |
- Flemme, Inger, 1947-
(författare)
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Health-related quality of life in recipients with an implantable cardioverter defibrillator due to life-threatening arrhythmias : a 5 year follow-up
- 2004
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general aim of this thesis was to describe self-reported health-related quality of life (HRQoL) in recipients with an implantable cardioverter defibrillator (ICD) due to life-threatening arrhythmias over a 5-year period. The design was prospective and longitudinal. Fifty-six patients participated in Paper I, and 35 of these patients, who had survived at least five years, were included in paper II. All patients had received their ICD as a form of secondary prevention. The Quality of Life Index-Cardiac version (QLI-C), Mishel Uncertainty in Illness Scale-Community version (MUIS-C), and multiple regression analysis were used. Higher scores indicate higher HRQoL and uncertainty. The questionnaires were completed on four occasions: before implantation, at three months and at 1 year and 5 years after implantation. ICD recipients were also asked how many shocks they had perceived. At the 5-year data collection, the average ICD recipient had lived with an ICD for 6 years and 9 months. In general HRQoL was lower at year 1 than at baseline (p = 0-033). A decrease in the socioeconomic domain was observed at year 1 (p = 0.006) but improved again at year 5 (p = 0.027) although it remained below the baseline value. ICD recipients' satisfaction with the family domain decreased from the time of the ICD implantation (p < 0.001) and from year 1 (p = 0.039) to year 5 after implantation. Uncertainty related to information had decreased at year 1 in relation to baseline (p < 0.001). A decrease in overall uncertainty was observed at year 5 in relation to year 1 (p = 0.009) as well as at year 6 in relation to baseline (p = 0.009). The longer the ICD recipient had lived with the device, the greater the risk of receiving a shock. However, ICD recipients who received shocks reported being less troubled by them over time. Uncertainty was identified as a predictor of Low HRQoL. The recipients reported a higher level of HRQoL at year 5 than at year 1. HRQoL was reasonably good 5 years after implantation, and the ICD recipients felt more secure and perceived their ICD as a lifesaver.
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| 23. |
- Fredriksson, Camilla, 1969-
(författare)
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Keratinocytes in tissue engineering of human skin: invitro and in vivo studies
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Full thickness wounds, such as deep burns, need restoration of both the dermal and epidermal layers of the skin. In normal wound healing, re-epithelialization occurs by migration and proliferation of keratinocytes from the wound edges and by differentiation of stem cells from remaining hair follicles. Restoration of dermis occurs by influx of growth factors secreted by macrophages, platelets, and fibroblasts; by fibroblast proliferation and subsequent synthesis and remodeling of collagenous dermal matrix. In the case of full-thickness acute burn injuries and chronic wounds (e.g. pressure ulcers, venous ulcers and diabetic foot ulcers), these processes are defective. With the principles of tissue engineering in mind (to correct, improve and maintain tissues and their functions), researchers have developed promising materials and methods to make it possible to restore either the dermal (Integra® DRT, Alloderm®) or the epidermal layer (split thickness skin grafts (STSG), cultured epithelial autografts (CEA), autologous keratinocytes in single cell suspension). It is now well established that superior results are obtained if both dermal and epidermal components are combined, for example in a bilayered skin equivalent. Apligraf® is recommended for use on venous ulcers and is the only bilayered living skin equivalent currently approved by the FDA. Studies on different factors affecting the wound healing capacity as well as techniques in use provide valuable information for further development.In this licentiate thesis, we evaluated different transplantation techniques for delivering cultured human keratinocytes in single cell suspension, a measure becoming more frequently used in addition to STSG and CEA for restoring the epidermal layer of the skin. We found that the pressure device, commonly used to spray cell suspension onto the wound with pressures as high as 200 kPa, killed around 0% of the cells. In comparison, an ordinary syringe with the attachment of a spray nozzle showed almost 90% viable cells post transplantation and provided an equally good distribution of the cell suspension.We also studied different silver containing dressings regarding silver accumulation in human skin. In addition, we graded the re-epithelialization to evaluate whether the dressings caused any delay in the wound healing process. We found that the silver dressings tested, with few exceptions, caused dermal accumulation of silver, primarily aggregated around blood vessels. We could also show that most of the dressings had negative effect on the re-epithelialization.For the restoration of the dermal layer of the skin, Integra® DRT functions as a scaffold for guided tissue regeneration of the dermis. We had the possibility to study a case of necrotizing fasciitis were the treatment consisted of the use of Integra® DTR together with sub-atmospheric pressure (after initial surgical debridement) and later transplantation of split thickness skin grafts. This measure proved to be safe as well as giving satisfactory pliable and aesthetically acceptable result.
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| 24. |
- Frödin, Ulla, 1958-
(författare)
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Health-related quality of life during and after stem cell transplantation
- 2013
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hematopoietic stem cell transplantation (HSCT) is an established treatment for a variety of malignant diseases, as well as a small proportion of non-malignant disorders. The treatment before the HSCT (called conditioning) can be either myeloablative (MAC) or given with reduced intensity (RIC). MAC is associated with high toxicity due to high doses of chemotherapy with or without total body irradiation (TBI), and is used in both autologous and allogeneic HSCT. In autologous HSCT the patient is the donor, and in allogeneic HSCT the donor is a sibling or an unrelated donor. RIC regimens are associated with reduced toxicity and are only for patients undergoing allogeneic HSCT. Both autologous and allogeneic HSCT have a strong effect on the patients’ health-related quality of life (HRQL). The two studies in this thesis were initiated when RIC was introduced at a hematological department in south-east Sweden in 2001. The overall purpose was to evaluate HRQL in patients undergoing HSCT. The studies covered the whole inpatient period and the following three years in order to have a comprehensive assessment of the patients’ HRQL over time. HRQL was assessed 13 times from baseline up to three years after HSCT with the instrument EORTC QLQ-C-30. The instrument consists of 30 items divided into three major domains: functional status, symptom status, and global health/QoL. Almost all functional scales, global health status/QoL, symptom scales and single items were significantly affected in the two studies during the first two to three weeks from baseline. The symptoms that patients estimated to be the most severe in the studies were nausea and vomiting, loss of appetite, fatigue, and diarrhea. Two months after HSCT nearly all functional scales, global health status/QoL, symptom scales and single items in Study I had returned to the same value as at baseline in patients undergoing autologous HSCT. It took up to two years for patients undergoing allogeneic HSCT in Study II to return to the same value as at baseline. For patients in Study I, role-, emotional-, and social function, fatigue and dyspnea had significantly improved at the 3-year follow-up compared to baseline, whereas role function was the only function that had improved in Study II. Patients with lymphoma in Study I experienced significantly worse HRQL in week 2 and appetite loss at month 2 than patients with multiple myeloma (MM). Patients treated with MAC in Study II had significantly worse fatigue and nausea and vomiting at baseline and pain, sleep disturbance, appetite loss and diarrhea at weeks 3 and 4 than patients treated with RIC. Patients with extensive chronic Graft versus Host Disease (GvHD) in Study II reported significantly impaired physical function, role function, and global health status/QoL than patients with limited or no chronic GvHD. These results provide a good overview of patients’ symptoms and HRQL during and after HSCT and indicate when they require increased support from healthcare professionals. The results also demonstrate the importance of close follow-ups during the first year after HSCT in order to improve preventive interventions. The quick recovery of patients in Study I suggests that the extensive treatment is well tolerated.
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| 25. |
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| 26. |
- Gustafsson, Gunnel
(författare)
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Quality of life and functional capacity among elderly with locomotor disability
- 1996
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of this study were to investigate the prevalence of locomotor disturbances among elderly and the consequences for their life situation, and to test two well-documented American tools on disabled elderly.Screening tests among elderly in two Swedish counties showed that 22 per cent of those aged 60 and above reported difficulties in mobility. Home visits were made to 90 persons in one of the counties, who were interviewed using the Philadelphia Geriatric Center Multilevel Assessment Instrument, PGC MAI, and the Quality of Life Index, QLI. There was a significant relationship between the domains representing activities of daily living, time use and mobility in the PGC MAl and a standardized functional test. A logical relationship was found between the domains of the PGC MAI and the subscales of the QLI. The instruments used in the study gave valid information and could be used for evaluating interventions among elderly.
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| 27. |
- Gustafsson, Thomas
(författare)
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Regulation and actions of insulin-like growth factor binding proteins in vascular smooth muscle cells
- 1999
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Insulin-like growth factor-I (IGF-I) has multiple actions on vascular smooth muscle cell (VSMCs) function. In the circulation and in extracellular fluids, IGF-I is complexed to high affinity IGF-binding proteins (IGFBPs), which modulate IGF-I bioactivity. The present study focused on expression and regulation of IGFBPs in VSMCs. and how they modulate IGF-1 effects in these cells.Rar VSMCs expressed mRNAs for IGFBP-2, -4 and -6, while human VSMCs expressed mRNAs for IGFBP-2, -3, -4, -5 and -6 as determined by solution hybridization. IGF-1 (10-8 M) increased and angiotensin TI (AII, 10-6 M) decreased IGFBP-2 and IGFBP-4 mRNA in rat VSMCs. Furthermore, AII and All and 1GF-I in combination increased IGF-I receptor mRNA and All decreased IGF-1 mRNA. We detected endogenous 1GFBP-2 and IGFBP-4 by Western immuno blot in concentrated conditioned medium of rat VSMCs. IGF-I did not affect steadystate levels of IGFBP-2 and -4, but increased the amount of fragments of these IGFBPs. Exogenously added IGFBP-2 and -4 were minimally degraded in serum free conditioned medium for up to 72h in the presence of VSMCs, but immunoreactive bands of the intact IGFBPs disappeared in the presence of IGF-I. We detected IGFBP-2, -4, -5 and -6 in concentrated conditioned medium of human VSMCs.IGFBP-1 and IGFBP-4 inhibited 1GF-1 (1 nM) induced DNA synthesis in rat VSMCs with IC50 values of 1.6 and 6.2 nM respectively, and they also inhibited IGF-I induced protein synthesis. IGFBP-2, if preincubated with IGF-I, also acted inhibitory on IGF-I action. IGFBP-1, -3 and- 4 (1.4-2.0 nM) inhibited IGF-I (I nM) induced DNA synthesis in human VSMCs, while IGFBP-2, -5 and -6 had no effects in these concentrations.IGF-I and AII had additive effects on DNA- and protein synthesis in rat VSMCs and these effects occurred at doses, at which the peptides added alone initiated DNA synthesis. Losartan blocked the synergistic effects and IGFBP-1, which inhibited IGF-I action, was not able to inhibit the action of AII.In conclusion, rat and human VSMCs express IGFBP-2, -4 and -6, but not IGFBP-1. The results on IGFBP-3 and IGFBP-5 are inconsistent. IGFBP-1, -3 and -4 act at physiological concentrations inhibitory on IGF-I stimulated effects. IGFBP-2 and IGFBP-4 are metabolized by proteases from rat and human VSMCs and the degradation of these IGFBPs is enhanced by IGF-I. There is an interaction of AII and the IGF-system in VSMCs and IGF-I and All have additive effects on DNA- and protein synthesis in these cells.
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| 28. |
- Gyllensvärd, Harald, 1980-
(författare)
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Health Economic Aspects of Injury Prevention at the Municipal Level
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Unintentional injuries are a global health problem, which in 1996 was estimated to cause up to 3 million deaths per year. In Sweden, about 4,600 people die annually due to external causes of morbidity and mortality (injuries and poisoning). Among children 1 to 17 years old, injuries are the leading cause of death in Sweden for both boys and girls. Injuries are also the leading cause of life years lost before age 65 in men and the second most common in women.Injury prevention interventions and programs can be implemented to mitigate the magnitude of this public health problem, the number of injuries in society, and the substantial costs associated with injuries. Society's resources are however limited and therefore it is pivotal that interventions are cost-effective and not only effective: that is, that they provide good value for money.Hence, the aim of this thesis was to develop new knowledge and improve decision making by elaborating on some of the important health economic aspects of injury prevention. Consequently, a critical appraisal of the existing cost-effectiveness studies on injury prevention interventions and estimations of the societal costs for different types of injuries that needed medical attention were conducted. The critical appraisal of studies was limited to those studies that investigated interventions that could be implemented by municipalities. The results shows that injuries are associated with substantial societal costs but differ considerably between different types of injuries. The average cost per injury was estimated at € 2,726 and varied between € 892 and € 15,537. Furthermore, the results indicate that there are injury prevention interventions that offer good use of societal resources. However, there is a general lack of economic evidence surrounding injury prevention interventions.This thesis has expanded the knowledge in some important health economic aspects of injury prevention. The generated knowledge may advantageously be used in future research, including cost-effectiveness analyses of injury prevention interventions, and assist in the targeting of new research. Future research should focus on estimating the cost-effectiveness of different interventions and the reductions in quality of life due to different injuries. Costeffectiveness data help decision-makers make judiciously resource allocation decisions that maximise health gain given limited budgets.
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| 29. |
- Hagert, Britt, 1945-
(författare)
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Patients' and cohabitants' reports after snoring surgery
- 1999
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general aim of this thesis was to evaluate the long-term effects of surgical treatment of snoring from the perspective of the patient and the cohabitant. In particular, the current snoring, daytime sleepiness and side effects have been investigated. A total of 415 (out of 457) patients operated on at a county hospital in Sweden during 1986-1992 and their 345 cohabitants have answered questionnaires, one for the patients and another one for the cohabitants.Surgery for snoring (uvulopalatopharyngoplasty = UPPP and laseruvulopalatoplasty = LUPP) reduced the occurrence of snoring and improved 89.7% of the patients, which was confirmed by 92% cohabitants. Eighteen per cent were free from snoring, and 25 % had no daytime sleepiness. Individuals with a shorter time since surgery reported less snoring. The UPPP method had significantly better result on snoring.Side effects from globus, regurgitation, taste, smell and voice were reported by 255 patients. Globus was most frequent, experienced by 161. These findings initiated a follow-up three years later of those who had reported side effects from taste, smell and voice (74).The number of patients reporting these side effects had decreased. The olfactory function was improved in seven persons. Many individuals reported other side effects from different spheres which remained a long time after surgery, such as pharyngeal dryness and problems with phlegm (60%). Of them 16-20 people found them serious. The globus also remained which to our knowledge has not been reported in the literature earlier.The majority of patients, even with side effects, were satisfied with the treatment and considered their status better or much better than before treatment. Looking back, if they had the choice again, 75% would choose surgical treatment for their snoring.
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| 30. |
- Hedbrant, Johan, 1959-
(författare)
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Särimner : a computer model for diabetes education
- 1993
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In diabetes mellitus pancreas fails to produce insulin enough to maintain tissue utilisation of blood glucose. To maintain a normalised metabolism many diabetic patients have to provide insulin from injections or an infusion pump. The disease affects some percent of western population.The insulin provided by the patient has to be adjusted to food and physical exercise. This may be achieved by following rules from diabetes professionals, but also by self learning how food, insulin and physical exercise interact and influence the blood glucose. It seems that the patients who have this intuitive knowledge of the interactions are the ones who manages their diabetes treatment best and have the highest quality of life. The learning have, however, been performed by trial and error - to the price of severe inconvenience and bad metabolic control.A combination of computer science and diabetes physiology has resulted in the computer program Särimner. It is created to give the user a possibility to experiment with diabetes treatment. Food, insulin and physical exercise may be varied and the blood glucose is calculated. Sarimner provides a short-cut to obtaining knowledge since it allows experiments, stimulates discussions and let the user by himself formulate and test hypotheses regarding experienced problems. Since Särimner may be adjusted to look more alike an individual, the experiments are driven by the user's own curiosity. He may experiment with situations of importance to himself and finally make himself the expert of his own treatment situation.The way Särimner is designed, allows interested users to get "under the skin" of the model and study details in the physiological processes. This transparency makes it possible to search for explanations to treatment phenomena. One drawback with the model is that it is quite complex and requires some knowledge from a user with the ambition to understand all the processes.To measure the impact of Särimner training, 11 diabetic teenagers were evaluated with respect to metabolic control, emotional adjustment, focus of control, self-esteem and ability to discuss treatment phenomena. No control group was possible to recruit.The results indicated that the education had been useful for some individuals. They increased their knowledge and ability to discuss treatment situations, their sense of control over the diabetes treatment, their self esteem and furthermore Särimner education may have caused a reduction of diabetes related stress. However, an increased level of diabetes related guilt did occur in some individuals, possibly due to either increased knowledge or a more internalised focus of control.The models ability to look alike reality is depending on for which purpose it is used. Even though it would be theoretically possible to fit the model to an individual, such an experiment would not be performable in reality since Särimner requires input data from the physiology which is impossible to measure. The properties of the model are, however, adequate for illustrating several treatment situations on a phenomenological level.
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| 31. |
- Heurtel Thuswaldner, Sophie, 1976-
(författare)
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Nucleotide-binding Proteins in the Plant Thylakoid Membrane
- 2006
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Life on Earth is dependent on the oxygen produced through photosynthesis. The thylakoid membrane is the site for the light-driven reactions of photosynthesis, which oxidize water and supply energy in the form of ATP, mainly for carbon fixation. The utilization of ATP in the lumenal space of the thylakoid has not been considered in the past. In the latest years, increasing evidence for nucleotide metabolism in the thylakoid lumen of plant chloroplasts has been presented; ATP transport across the thylakoid membrane, and GTP binding to the PsbO extrinsic subunit of the water-oxidizing photosystem II (PSII) complex.In this thesis, various methods for prediction, identification, and characterization of novel plant proteins, are described. Nucleotide-binding motifs and nucleotide-dependent processes are reviewed, and the experimental data is discussed. 1) A thylakoid ATP/ADP carrier (TAAC) in Arabidopsis thaliana was identified and functionally characterized, and 2) the spinach PsbO protein was characterized as a GTPase. The Arabidopsis At5g01500 gene product is predicted as a chloroplast protein and to be homologous to the well-studied mitochondrial ADP/ATP carrier. The putative chloroplast localization was confirmed by transient expression of a TAAC-green fluorescent protein fusion construct. Immuno detection with peptide-targeted antibodies and immunogold electron microscopy showed the thylakoid as the main localization of TAAC, with a minor fraction in the chloroplast envelope. TAAC is readily expressed in etiolated seedlings, and its level remains stable throughout the greening process. Its expression is highest in developing green tissues and in leaves undergoing senescence or abiotic stress. It is proposed that the TAAC protein supplies ATP for energy-dependent reactions during thylakoid biogenesis and turnover. Recombinant TAAC protein was functionally integrated in the cytoplasmic membrane of Escherichia coli, and was shown to specifically transport ATP/ADP in a protonophore-sensitive manner, as also reported for mitochondrial AACs.The PsbO protein stabilizes the oxygen-evolving complex of PSII and is ubiquitous in all oxygenic photosynthetic organisms, including cyanobacteria, green algae, and plants. So far only the 3D-structure of the cyanobacterial PsbO is available. Four GTP-binding motifs in the primary structure of spinach PsbO were predicted from comparison with classic GTP-binding proteins. These motifs were only found in the plant PsbOs, in the -barrel domain of the homologous 3D-structure. Using circular dichroism and intrinsic fluorescence spectroscopy, it was shown that MgGTP induces specific structural changes in the PsbO protein. Spinach PsbO has a low intrinsic GTPase activity, which is considerably stimulated when associated with a dimeric PSII complex. GTP stimulates the dissociation of PsbO from PSII under both inhibitory and non-inhibitory light conditions. A role for PsbO as a GTPase in the function of the oxygen-evolving complex and PSII repair is proposed.
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| 32. |
- Holstein, Jane, 1970-
(författare)
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Cultural Competence for Health Professionals : Instrument Development
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In recent decades, both global migration in general and specifically migration to Sweden have increased. This development compels the need for delivering healthcare to the increasingly diverse populations in Sweden. To support health professionals, for instance occupational therapists, in developing their professional knowledge in encounters with foreign-born clients a self-rating instrument measuring cultural competence is developed. This may contribute to the development of suitable services for foreignborn clients and improve person-centered interventions for these clients.The general aim of this thesis was to develop an instrument for health professionals by examining psychometric properties and utility of the Swedish version of the Cultural Competence Assessment Instrument (CCAI-S) among occupational therapists. The specific aim of study I was to evaluate the content validity and utility of the Swedish version of the Cultural Competence Assessment Instrument (CCAI-S) among occupational therapists. The study had a descriptive and explorative design. Nineteen occupational therapists participated, divided into four focus groups. Qualitative content analysis was used to examine the content validity and utility of the CCAI-S. The specific aim of study II was to examine the clinical relevance, construct validity and reliability of the Swedish version of the Cultural Competence Assessment Instrument (CCAI-S) among Swedish occupational therapists. The study had a cross-sectional design. A web-based questionnaire was e-mailed to a randomised sample of 428 occupational therapists to investigate the construct validity, reliability and utility of the CCAI-S. Factor analysis was performed as well as descriptive statistics.The findings from study I revealed high content validity for all 24 items. However, six items needed reformulations and exemplifications. Regarding utility, the results showed strong support for CCAI-S. The category ‘Interactions with clients’ showed that the CCAI-S could be utilised individually for the health professional and create a higher awareness of cultural questions in practice. The category ‘Workplace and its organisational support’ displayed potential for use in different workplaces regarding CCAI-S and indicated the importance of organisational support for health professionals in the development of cultural competence. The findings from study II regarding construct validity generated a three-factor model with the labels ‘Openness and awareness’, ‘Workplace support’ and ‘Interaction skills’. All three factors showed high factor loadings and contained 12 of the 24 original items. The Cronbach’s Alpha showed high support for the three-factor model. Concerning utility, the participants reported that all 24 items had high clinical relevance.In conclusion, the findings from the two studies indicated good measurement properties and high clinical relevance for the CCAI-S. This may sup-port the utilisation of CCAI-S in the Swedish context for health professionals, for instance occupational therapists. The results of the instrument development show that the upcoming published version of the CCAI-S can be a valuable self-assessment tool for health professionals who strive to improve in person-centred communication in encounters with foreign-born clients. CCAI-S can also be of support for the organisation to serve as a guide for what to focus on to develop cultural competence within the staff. Altogether this presumably influence the effectiveness of the healthcare and enhance the evidence of interventions for foreign-born clients. To develop an instrument is an iterative process requiring several evaluations and tests in various settings and populations. Therefore further psychometric testing and utility studies on the CCAI-S is crucial.
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| 33. |
- Hällgren, Mathias, 1972-
(författare)
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Assessment of central auditory functions : methods and applications
- 2001
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Central auditory processing is complex and can not be completely evaluated by a single method. This thesis focuses on assessment of some aspects of central auditory functions by the use of dichotic speech tests, cognitive tests that tax functions important for speech processing and electrophysiological tests.Paper A deals with the cognitive effects in dichotic speech testing in elderly hearing impaired subjects. Dichotic speech tests and cognitive tests were performed on 30 hearing impaired subjects ranging in age from 42 to 84 years. The dichotic test material consisted of digits, short sentences and consonant-vowel-syllables. The cognitive test material comprised tests for short-term memory, verbal information processing and phonological processing. Effects of age in dichotic speech tests in elderly were verified. The degree of effect was dependent upon focusing condition and test material. The different listening tasks in the dichotic tests put different demands on cognitive ability, shown by a varying degree of correlation between cognitive functions and dichotic test parameters. Age-related cognitive decline in the elderly was strongly connected with problems to perceive stimuli presented to the left ear.Paper B presents a new cognitive test battery, performed in text, auditory and audiovisual modalities. The tests are sensitive for functions important for speech processing and understanding. The test battery was evaluated in four groups, differing in age and hearing status. Each group comprised twelve subjects. The effect of low-level noise on cognitive functions was investigated. The only significant result in the text modality was an age effect in speed of performance, which was also seen in the auditory and audiovisual modalities. In the auditory and audiovisual modalities effects of hearing status and modality were seen in accuracy parameters. Interaction between hearing status and modality, both in accuracy and speed of performance, shows that hearing-impaired subjects benefit more from visual cues. In noise generally poorer results were obtained, especially in the auditory modality and for the elderly, affecting both accuracy and speed. The test battery has proven to be useful in assessing the relative contribution of different input-modalities and the effect of age, hearing-impairment and visual contribution on functions important for speech processing.Paper C describes the development of a system for recording of auditory evoked potentials. The system is built around a personal computer with a data-acquisition board with analogue input and output channels. Acoustic stimuli are presented to the test subject and responses to the acoustic stimuli are recorded in an EEG-recording system. The program is written in the graphical programming environment LabView (National Instruments). With the system it is possible to perform all clinical standard measurements. In addition, test-procedures not available in commercial auditory evoked potential systems have been developed. For the assessment of auditory discrimination a toolkit for evaluation of the mismatch negativity potential was developed and evaluated in six normal-hearing subjects.
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| 34. |
- Idvall, Ewa, 1950-
(författare)
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Strategic and clinical quality indicators in surgical nursing care
- 1998
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general aim of this study was to identify strategic and clinical quality indicators in surgical nursing care. The methods used were a literature review, focus group interviews and a survey with a questionnaire.In the literature the most frequently found definition of a clinical indicator was "a quantitative measure that can be used as a guide to monitor and evaluate the quality of important patient care and support activities". To uncover clinical nurses' perceptions of important aspects of surgical nursing care, four focus group interviews were undertaken. A tentative model with two dimensions and fifteen categories emerged from the data analysis. This model was used as a base for designing items to be effective as strategic and clinical quality indicators in postoperative pain management. A questionnaire to 233 clinical nurses was compiled to establish the usefulness and relevance of the items designed. Generally, all the items had high scores as being essential, realistic to carry out, and possible for nurses to influence. The tentative model was found useful for designing items that might be effective as strategic and clinical quality indicators in postoperative pain management.
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| 35. |
- Irander, Kristina, 1943-
(författare)
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An 18 year Follow-up of Allergy Development : Findings of Nasal Markers of Allergic Inflammation
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: In addition to the family history of allergy (FH), there is a need o find objective markers of allergy development as early in life as possible in order to focus preventive measurements on high risk infants. Rhinitis problems are common causes to morbidity in adults due to allergic as well as non-allergic mechanisms. Accurate diagnoses are essential for decisions of optimal management of the patients, but in non-allergic rhinitis groups there are no objective tests to verify the diagnosis, if this is needed.Aims: The primary aim was to evaluate the occurrence of nasal metacromatic (MC) cells during infancy as predictors for allergy development in a group of high risk subjects from birth up to 18 years of age. Additional aims were to find and evaluate nasal markers with ability to differentiate between allergic rhinitis with and without current allergen exposure from normal controls.Subjects and methods: New-borns (n = 67) with and without family histories of allergy were included, and during the first 18 months of life occurrence of nasal MC could be evaluated in 64 infants (33 positive/31 negative MC findings). The cohort was followed up for allergy development at the ages of 18 months, 6 years and 18 years. Nasal markers as MC, nasal NO, nitrite/nitrate in nasal lavage and acoustic rhinometry at the 18-years follow-up were related to the allergic manifestations at this age.Results: Positive nasal MC findings during infancy predicted allergy development up to 18 years of age in 31/33 subjects (94 %), as compared to 37/44 with positive FH (84 %). Negative MC findings during infancy did not exclude the risk, as 15/31 developed allergy (48 %). At the 18-years follow-up the numbers of individuals with demonstrable MC were significantly higher (p = 0.01) in the group of individuals with allergy symptoms (16/30) compared to the group of individuals with no allergy (1/12). Nasal NO levels, nitrite/nitrate concentrations in nasal lavages and acoustic rhinometry did not differentiate the allergic groups from the normal group.Conclusions: Positive nasal MC findings during infancy predicted allergy development up to 18 years of age, and the cell findings often preceded the allergic symptoms. The marker can not be used as a single predictor of allergy development due to negative MC findings in a high proportion of allergic subjects. Positive MC findings combined with positive FH resulted in the best the risk evaluation. Differences between groups with and without current allergen exposure and healthy controls were not found by means of acoustic rhinometry, nasal MC, nasal NO or nitrites/nitrates levels. Further research to find reliable nasal markers is needed.
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| 36. |
- Jakobsson, Tell, 1951-
(författare)
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Lactobacilli dominating the normal vaginal flora
- 2003
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The microbiology of the ecological niche of the vagina is dynamic. There are numerous inhabitants, mainly anaerobic bacteria. During the fertile years the vaginal mucosa is normally dominated by lactobacilli, a fact that has been known for over a century. Lactobacilli are a phenotypically heterogeneous group of bacteria that first became possible to identify to the species level with some precision using recently developed nucleic acid based techniques. In this study vaginal fluid was cultured from women scheduled for their regular PAP smear. Two hundred and two isolates from 23 women with normal vaginal fluid were typed by randomly amplified polymorphic DNA (RAPD) PCR analysis and identified to the species level by temporal temperature gradient gel electrophoresis (TTGE), and 16S rDNA sequencing. Four hundred and four isolates from 23 women were typed with broad range PCR of 16S rRNA gene region V I and V3 by pyrosequencing. Most women harboured one single species, a few had two different species, and only one woman harboured more than two different species of lactobacilli. The species that were found, which were similar in the two studies, were: Lactobacillus crispalus, L. gasseri, L. jensenii and L. iners. L. iners has never been reported before as a member of the dominant normal vaginal lactobacillary flora. Under some conditions, which have not been determined with certainty, the lactobacilli are overgrown by large amounts of Gardnerella vaginalis and anaerobic bacteria, mainly Bacleroides spp and Mobiluncus, causing the syndrome of Bacterial Vaginosis (BV). BV is associated with several severe reproductive and genitourinary complications in women. A major issue in studying normal Lactobacilli in vaginal fluid samples from women of reproductive age is to differentiate the normal flora from that of BV. To sharpen the diagnostic tools (i.e. Nugent scoring of Gram stained slides) for separation of normal flora from that of BV, a workshop was set up. The major results showed discrepancies in diagnosis when there were very few lactobacilli. There was disagreement on where to delimit small lactobacilli from G. vaginalis and Bacteroides. The use of scoring to delimit normal flora, as was done in the workshop, is proposed as a prerequisite for further studies of normal vaginal flora
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| 37. |
- Jerhammar, Fredrik, 1979-
(författare)
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On Predictive Factors of Treatment Response in Head and Neck Squamous Cell Carcinoma
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and yearly include 500 000 new cases worldwide. The outcomes for these patients have not been significantly improved over the last decades and the five year survival is still around 50 %. Establishing predictive markers of treatment response will have great impact on the clinical management of this disease.The aim of this thesis was to elucidate markers of intrinsic response to radiotherapy and cisplatin. Combining expression patterns of 14 proteins and identifying mutations in the p53 gene, we were able to incorporate both protein and genetic changes to create a predictive model termed Number of Negative Points (NNP). We used the NNP model to statistically calculate the combination of factors that had the best correlation to intrinsic radiosensitivity (IR). We established that a panel of three markers, epidermal growth factor receptor (EGFR), survivin and splice site/missence mutations of p53, had the best correlation to IR (R=0.990, p<0.0001).We also conducted gene expression analysis to investigate what genes and gene ontologies that are different between cell lines with varying IR. Furthermore, we wanted to identify key regulator genes with central positions of molecular networks, which were generated from the transcripts included in the deregulated gene ontologies. A transcriptional profile of 28 key regulator genes was generated. Immunoblot analysis supported deregulation at the protein level of three markers implicated from the transcriptional profile. We propose that these proteins, notch1, thrombospondin 1, and pai‐1 are predictive markers of IR.Finally, on a subset of cell lines with sensitivity or resistance to cisplatin, we performed gene expression analysis. Markers of intrinsic cisplatin sensitivity (ICS) such as gene ontologies and key regulators of molecular networks were proposed and five genes, APOE, CTNNB1, MMP7, MMP13, and THBS1 were selected for further analysis. Quantitative polymerase chain reaction (qPCR) analysis of these genes in 25 cell lines established that MMP7 (p=0.0013) and MMP13 (p=0.058) are possible predictive markers of ICS.The markers of IR and ICS presented here could, if confirmed in a clinical setting, guide clinicians in the choice of treatment and thus give a more individualized and effective therapy for patients with HNSCC.
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| 38. |
- Johannesson, Eva, 1946-
(författare)
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Learning manual and procedural clinical skills through simulation in health care education
- 2012
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general aim of this thesis was to contribute to a deeper understanding of students’ perceptions of learning in simulation skills training in relation to the educational design of the skills training. Two studies were conducted to investigate learning features, what clinical skills nursing students learn through simulation, and how.Undergraduate nursing students were chosen in both studies. Study I was conducted in semester three, and study II in semester six, the last semester. Twenty-two students in study I practised intravenous catheterisation in pairs in the regular curriculum with an additional option of using two CathSim® simulators. In study II, ten students practised urethral catheterisation in pairs, using the UrecathVision™ simulator. This session was offered outside the curriculum, one pair at a time.In study I, three questionnaires were answered - before the skills training, after the skills training and the third after the skills examination but before the students’ clinical practice. The questions were both closed and open and the answers were analysed with quantitative and qualitative methods. The results showed that the simulator was valuable as a complement to arm models. Some disadvantages were expressed by the students, namely that there was no arm model to hold and into which to insert the needle and that they missed a holistic perspective. The most prominent learning features were motivation, variation, realism, meaningfulness, and feedback. Other important features mentioned were a safe environment, repeated practice, active and independent learning, interactive multimedia and a simulation device that was easy to use.In study II the students were video-recorded during the skills training. Afterwards, besides open questions, the video was used for individual interviews as stimulated recall. The interview data were analysed with qualitative content analysis. Three themes were identified: what the students learn, how the students learn, and how the simulator can contribute to the students’ learning. When learning clinical skills through simulation, motivation, meaningfulness and confidence were expressed as important factors to take into account from a student perspective. The students learned manual and procedural skills and also professional behaviour by preparing, watching, practising and reflecting.From an educational perspective, variation, realism, feedback and reflection were seen as valuable features to be aware of in organising curricula with simulators. Providing a safe environment, giving repeated practice, ensuring active and independent learning, using interactive multimedia, and providing a simulation tool that is easy to use were factors to take into account. The simulator contributed by providing opportunities to prepare for skills training, to see the anatomy, to feel resistance to catheter insertion, and to become aware of performance ability. Learning features, revealed from the students’ thoughts and experiences in these studies, are probably general to some extent but may be used to understand and design clinical skills training in all health care educations. In transferring these results it is important to take the actual educational context into account.
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| 39. |
- Johnson, Christina, 1964-
(författare)
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Telephone advice nursing : communication, patient satisfaction and tool development
- 2018
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Telenursing has rapidly expanded in many countries. In Sweden, a national telephone advisory nursing service reaches the entire nation and receives approximately 4,5 million calls per year. The six phase nursing process – assessment, nursing diagnosis, setting goals, planning, implementation and evaluation – can be used when managing a caller’s health problem. In telenursing, a person-centred approach makes for more satisfied and appreciative callers. The core component of interaction is the verbal communication between the telenurse and caller. Several studies have revealed the need for the development of communication competence in telenursing. Structured analyses of conversations between telenurses and callers is one way to increase telenurses’ awareness of their communication and interpersonal competence. This type of analysis requires a valid formative self-assessment tool. To evaluate communicative effectiveness, the patient perspective of the interpersonal aspects of interaction are described as a necessary component, and satisfaction surveys designed for a telenursing context are recommended. Therefore, a questionnaire is needed that evaluates the effects of telenurse communication training from the caller’s perspective.Aims: The overall aim of these two studies was to develop tools to enable improvements and evaluations in communication and interpersonal competence in telenursing from the perspective of both the telenurse and the caller.Study 1: To develop a self-assessment tool aiming to raise telenurses’ awareness of their communication and interpersonal competence and highlight areas in need of improvement.Study 2: To develop and assess content validity of a theoretically anchored questionnaire that explores caller satisfaction in TAN as a result of the interaction between the caller and the telenurse.Methods: Study 1: The development and the evaluation of content validity of the Telenursing Self-Assessment Tool (TSAT) started with a literature search and domain identification, which were used to generate the items. The assessment of the content validity was performed in two steps. First, an expert group completed two rounds of assessments using Content Validity Index (CVI). Second, telenurses tested the tool and assessed the content validity using CVI. Thereafter, the telenurses participated in consensus discussions. Refinements of the tool were done after every assessment.Study 2: The development and the evaluation of content validity of the Telenursing Interaction and Satisfaction Questionnaire (TISQ) started with a literature search and domain identification, which were used to generate the items. The assessment of the content validity was performed in two steps. First, cognitive interviews were performed with the callers, the target population. Next, experts evaluated the content validity using CVI. Refinements of the tool were done after every assessment. The Interaction Model of Client Health Behavior (IMCHB) provided theoretical guidance and support.Results:Study 1: The TSAT with 58 items was developed. The items were structured according to the nursing process and the tool was judged as having good content validity.Study 2: The TISQ consisting of 60 items based on the IMCHB was developed. The questionnaire was found to exhibit good content validity.Conclusions: This thesis describes the development and assessment of content validity of two theoretically anchored tools aimed to improve and evaluate communication and interpersonal competence in telenursing from the perspective of both the telenurse and the caller. The TSAT is meant to create learning opportunities, to provide self-direction, feedback, and coaching, and to guide the telenurse through the nursing process using a person-centred approach. The TISQ aims to explore the callers’ satisfaction and the callers’ perceptions of the interaction with the telenurse. With better knowledge about this, communication improvement and education in telenursing can be tailored to enhance caller satisfaction.
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| 40. |
- Jonasson, Lise-Lotte, 1956-
(författare)
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Ethical values in caring encounters from elderly patients’ and next of kin´s perspective
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The welfare of the elderly population is one of the most important goals of the public health services. At macro level the Swedish National Board of Health and Welfare state that the premier goal is for elderly people to have dignified and comfortable lives. They should have a life with a sense of value and feel confident. These ethical values which are expressed on macro level or as normative ethics are expected to prevail at micro level. In our study the micro level is the caring encounter between the elderly patient, next of kin and nurses. Ethical values and morals are important aspects that influence the quality of care, videlicet in empiric ethics.The aim of study (I) was to identify and describe the ethical values experienced by the older person in the daily interaction with nurses in a ward for older people during caring encounters. In study (II) the aim was to identify and describe the governing ethical values that next of kin experience in interaction with nurses who care for elderly patients at a geriatric clinic. Study (I) which was an empirical observational study included follow-up interviews. Twenty-two older people participated voluntarily. In study (II) interviews with fourteen next of kin were conducted. In both studies Constant comparative analysis, the core foundation of grounded theory was used.Five categories; Being addressed, receiving respect, desiring to participate, increasing self-determination and gaining self-confidence formed the basis for the core category in study (I): Approaching. Approaching concerns the way people become closer to each other in a physical space .It also includes how people become closer to each other in a dialogue, which involves verbal or bodily communication. Approaching indicates the ethical values that guide nurses in their caring encounters with older people. This ethical value is noted by the older person and has an individual value, as well as leading to improved quality of their care. The older person will be confident and satisfied with the caring encounter if the desired components in the nurse’s approaching are exhibited.Four categories were identified in study (II): Receiving, showing respect, facilitating participation and showing professionalism. These categories formed the basis of the core category: “Being amenable”, a concept identified in the next of kin’s description of the ethical values that they and the elderly patients perceive in the caring encounter. Being amenable means that the nurses are guided by ethical values; taking into account the elderly patient and next of kin. Nurses who focus on elderly patients’ well-being as a final principle will affect next of kin and their experience of this fundamental situation.
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| 41. |
- Karlsson, Agneta, 1949-
(författare)
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Transition towards autonomy and psychological empowerment in self-management, among teenagers with type 1 diabetes
- 2007
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general aim of this thesis was to study the transition process from dependency towards anatomy and psychological empowerment among teenagers with type 1 diabetes. Thirty-two teenagers (18 female/14 male) aged 13-17 took part in conversational interviews. The interviews followed a semi-structured question guide. Data comprised 31 tape recorded interviews (one informant did not want to be tape recorded). The research design was based on a phenomenological and life world perspective including two different analysis methods.The transition towards autonomy among teenagers with type 1 diabetes was elucidated in a phenomenological approach (paper I). Through the teenagers’ narratives about their daily life experiences with type 1 diabetes there emerged the over-riding theme “Hovering between individual actions and support of others”. This theme illustrates the main problem related to diabetes management - duality in dependence and independence. The themes “growth through individual self-reliance” and “growth through confirmation of others” seem to facilitate the transition process from dependency towards autonomy. Experiences of the Empowerment Education Programme (EEP) were studied by a qualitative content analysis (paper II). From the teenagers’ descriptions the over-riding theme was formulated as “Sense of community”, and this covered the categories of social fellow feeling, collaborative learning, and community of interests. A synthesis of the findings illustrates that individual self-reliance, confirmation of others, and sense of community are closely related to individual inner resources, trust in others, and the feeling of belonging, which are all suggested as specific goals of empowerment and fulfilment of psychological empowerment. A model was created to explain the relation between psychological empowerment and growth through individual self-reliance, confirmation of others, and sense of community. Professional nursing care might start from the unique situation and context the individual experiences and exists in. Social meetings with like-minded youth were highly appreciated among the teenagers. The teenagers showed their willingness to transform themselves towards becoming more independent in self-management, and the teenage years may be the right period to empower and coach the teenagers towards autonomy and prepare them for adulthood living with type 1 diabetes.
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| 42. |
- Karlsson, Helen, 1961-
(författare)
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Lipoproteomics : mapping of proteins in LDL and HDL
- 2005
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- High-density lipoprotein (HDL) and (LDL)-density lipoprotein (LDL) are important lipoprotein fractions in human plasma. HDL is the most abundant lipoprotein particle and a negative risk factor of atherosclerosis while LDL is considered to possess atherogenic properties. The molecular mechanisms underlying the relationship between LDU/HDL and the development of atherosclerosis are not clear. Therefore, detailed information about the protein composition of LDU/HDL may contribute to reveal their role in atherogenesis and the mechanisms that lead to or protect from coronary disease in humans. Here, we sought to map the proteins in human LDL/HDL by a proteomic approach.LDL and HDL were isolated by two-step discontinuous density-gradient ultracentrifugation and the proteins were separated with two-dimensional gel electrophoresis and identified with peptide mass fingerprinting, using matrix assisted laser desorption/ionization-time of flight-mass spectrometry and with amino acid sequencing using electrospray ionization tandem mass spectrometry.In LDL these procedures identified apo B-100, apo C-II, apo C-I (three isoforms), apo E (four isoforms), apo A-I (three isoforms), apo A-IV, apo J and apo M (three isoforms not previously described). In addition, three proteins that have not previously been identified in LDL were found: serum amyloid A-IV (two isoforms). calgranulin A and lysozyme C. The identities of apo M, calgranulin A, and lysozyme C were confirmed by sequence information obtained after collision-induced dissociation fragmentation of pep tides characteristic for these proteins. Moreover, the presence of lysozyme C was further corroborated by demonstrating enriched hydrolytic activity in LDL against Micrococcus lysodeikticus.Identified proteins in HDL were: the dominating apo A-1 as seven isoforms, four of them with a modification pattern and one of them with retained propeptide, apo A-II, apo A-IV, apo C-I. apo C-II, apo C-III (two isoforms), apo E (five isoforms), apo J, the recently discovered apo M (two isoforms), serum amyloid A (two isoforms) and serum amyloid A-IV (six isoforms). Furthermore, alpha-1-antitrypsin was identified in HDL for the first time. Additionally, salivary alpha-amylase was identified as two isoforms in HDL2 , and apo L and aglycosylatcd apo A-II were identified in HDL3.These results indicate that both LDL and HDL contains a number of apolipoproteins, many of them occurs in different isoforms. The demonstration, for the first time, that LDL contains calgranulin A, lysozyme C and apo J raises the possibility that LDL proteins may play hitherto unknown role(s) in immune and inflammatory reactions of the arterial wall. Additionally, new patterns of glycosylated apo A-I and apo A-II and new proteins; alpha-1-antitrypsin and salivary alpha-amylase were detected in HDL. Further investigations about these proteins may give new insight into the functional role of LDL and HDL in coronary artery disease.
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| 43. |
- Karlsson, Lisa, 1980-
(författare)
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Differentiation of Human Dermal Fibroblasts : a New Tool in Vascular Tissue Engineering
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tissue engineering is an expanding field, which focuses on the development of func-tional substitutes for damaged tissues. A limitation in this field is difficulties with obtaining autologous cells. Recent research has shown the presence of cells with multilineage-potential within the connective stroma of the skin. In line with this, a potential plasticity inherent in human dermal fibroblasts has been demonstrated. The overall aim of this study was to investigate if human dermal fibroblasts can be used as a cell source for vascular tissue engineering. Differentiation towards an endothelial cell-like phenotype was induced by culturing dermal fibroblasts in endothelial growth medium. By utilizing in vitro cell culture models, the capacity of different types of serum and serum constituents in inducing a phenotypic shift in fibroblasts was investi-gated. To clarify the mechanisms behind this phenotypic shift and to eliminate the risk of having growth of residual endothelial cells in the cultures, both normal dermal fibroblasts and single-cell clone fibroblasts were used. Our results demonstrated that presence of human serum caused fibroblasts and single-cell clone fibroblasts to express vWf, to incorporate fluorochrome-labeled low-density lipoprotein, and to start form-ing capillary-like networks. As an initial step in using these cells in tissue engineering, their ability to endothelialize a surface in vitro was studied. Cells cultured in either fibroblast or endothelial growth medium were seeded on scaffolds. Differentiation was confirmed by western blotting and immunohistochemistry using antibodies directed towards vWf, ve-cadherin, eNOS, and bradykinin receptor B2. The results revealed that endothelial differentiated fibroblasts cultured on scaffolds showed histological resem-blance to endothelial cells, and expressed molecules indicative of an endothelial phenotype. In conclusion, the results presented in this study indicate a possibility to induce differentiation of human dermal fibroblasts towards an endothelial cell-like phenotype. Consequently, these data suggests that human dermal fibroblast may be a novel cell source for vascular tissue engineering.
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| 44. |
- Klang Årstrand, Hanna
(författare)
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Phosphoproteomic analysis of Arabidopsis thaliana ribosomes
- 2012
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ribosomes serve as the site of protein synthesis in all living cells. Ribosomes were discovered in 1955 by George E. Palade when he was studying the endoplasmic reticulum which is covered by ribosomes. He received the Nobel Prize in Physiology or Medicine in 1974 for this discovery. Ribosomes are large protein and rRNA complexes which are made up from one small and one large subunit that work together to translate mRNA into a protein chain. Eukaryotic translation is mainly controlled during the initiation, which involves protein phosphorylation. In plants there is a general increase of protein synthesis during the day in order to synthesize proteins needed for photosynthesis. Phosphorylation can alter protein function and localization and is reversibly added and removed by kinases and phosphatases, respectively.The aim of the studies in this thesis was to elucidate the phosphorylation status of ribosomal proteins in the Arabidopsis thaliana 80S ribosome. I have focused on comparing ribosomal protein phosphorylation between different conditions and sub cellular locations, namely day/night conditions and cytosol/nucleus location.By using Fe3+IMAC to enrich phosphorylated peptides from cytosolic ribosomes followed by mass spectrometric analysis eight serine residues in six ribosomal proteins were found to be phosphorylated. Among these was a novel phosphorylation site in 40S ribosomal protein S6 at Serine 231. By using quantification with stable isotope labeling and mass spectrometry this phosphorylated residue and three other ribosomal phosphopeptides were found to have increased phosphorylation levels during day as compared to night ranging from 2 to 4 times. This phosphorylation increase can in turn effect the modulation of the diurnal protein synthesis in Arabidopis thaliana.Ribosome biogenesis involves shuttling of proteins and ribosomal subunits between the cell nucleus and cytoplasm. By purifying ribosomal proteins from these two cellular compartments and enriching for phosphopeptides using TiO2 affinity chromatography combined with mass spectrometry I was able to analyze their phosphorylation status. This method identified 13 phosphopeptides derived from 11 ribosomal proteins as well as phosphopeptides from two ribosomal associated proteins. 40S ribosomal protein S2-3 was found phosphorylated only in the cytoplasmic samples while 60S ribosomal protein L13-1 and the two ribosomal associated proteins were found only in the nuclear enriched samples.
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| 45. |
- Klasson, Anna, 1973-
(författare)
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MRI Contrast Enhancement using Gd2O3 Nanoparticles
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is an increasing interest for nanomaterials in biomedical applications and in this work, nanoparticles of gadolinium oxide (Gd2O3) have been investigated as a novel contrast agent for Magnetic Resonance Imaging (MRI). Relaxation properties have been studied in aqueous solutions as well as in cell culture medium and the nanoparticles have been explored as cell labeling agents. The fluorescent properties of the particles were used to visualize the internalization in cells and doped particles were also investigated as a multimodal agent that could work as a fluorescent marker for microscopy and as a contrast enhancer for MRI.Results show that in aqueous solutions, there is a twofold increase in relaxivity for Gd2O3 compared to commercial agent Gd-DTPA. In cell culture medium as well as in cells, there is a clear T1 effect and a distinct increase in signal intensity in T1-mapped images. Fluorescent studies show that the Gd2O3 nanoparticles doped with 5% terbium have interesting fluorescent properties and that these particles could work as a multimodal contrast agent.This study shows that Gd2O3 nanoparticles possess excellent relaxation properties that are retained in more biological environments. Gd2O3 particles are suitable as a T1 contrast agent, but seem also be adequate for T2 enhancement in for instance cell labeling experiments.
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| 46. |
- Knaust, Eva, 1944-
(författare)
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Heterogeneity of leukemic cells with regard to daunorubicin accumulation and efflux : potential role in drug resistance
- 2000
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cellular resistance to chemotherapy is a major cause of treatment failure in acute myelocytic leukemia (AML) and other malignancies. Drug resistance is multifactorial; the most studied mechanism being multidrug resistance (MDR), mediated by the P-glycoprotein (PPG), a transmembrane transport protein with a pump function, encoded by the mdr 1 gene. MDR is characterised by cross resistance to a wide range of chemotherapeutics of natural origin e.g. anthracyclines, vinca alkaloids, epipodophyllotoxins and taxanes. The aim of the present study was to elucidate transport kinetics of the anthracycline daunorubicin (Dnr) and to study various forms of heterogeneity in cells from patients with AML. The ultimate goal is to improve treatment based on each patient's individual resistance patterns.Density gradient isolated mononuclear cells from patients with AML were incubated with Dnr. Incubated cells were sorted on the basis of accumulation of the autofluorescent Dnr with flow cytometry. Gene expression of the Pgp and the multidrug resistance-associated protein (MRP) in sorted subpopulations were analysed with polymerase chain reaction (PCR). Drug accumulation and efflux in leukemic cell populations, apoptosis, expression of p53 and bcl-2 in the sorted subpopulations were studied with flow cytometry.Gene expressions of mdrl and mrp were shown to be heterogeneous in the leukemic samples and drug accumulation correlated inversely to the gene expression. The blast cell population differed in drug accumulation and efflux compared to the total mononuclear cell population that contains also normal lymphocytes and monocytes. In leukemic samples with two blast cell populations the more immature blast cells accumulated less drug and had a higher efflux rate than the differentiating blast cells. Cell populations with higher drug accumulation entailed more apoptosis.The results suggest that, since several resistance factors can occur in the same patient heterogeneity in the leukemic cell population ought to be taken into account whenever resistance patterns are studied.
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| 47. |
- Kvarnström, Susanne, 1958-
(författare)
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Interprofessionella team i vården : En studie om samarbete mellan hälsoprofessioner
- 2007
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There are great expectations that collaboration among professions and various sectors will further develop health care and thus lead to improved public health. In the World Health Organization’s declaration “Health 21” the designated goal for health professions in the member nations in Europe by the year 2010 is to have developed health promotional competence, including teamwork and cooperation based on mutual respect for the expertise of various professions. The challenges faced by the interprofessional teams are, however, multifaceted, and these challenges place demands upon society, which, in turn, determines the fundamental conditions for collaboration among the health professions within the health care organizations.This licentiate dissertation contains discourse and content analyses of interprofessional teamwork in health care. The major objective of this dissertation is to study and describe how the team members construct and create the content and significance of teams and teamwork among health professions. One specific goal has been to study how the members of a multi-professional health care team refer to their team, especially the discursive patterns that emerge and the function that these patterns has (I). The second specific goal has been to identify and describe the difficulties that the health professionals have experienced within their interprofessional teamwork. One purpose has been to enable discussions of the implications for interprofessional learning (II).Focused group interviews with team members (n=32) from six teams were studied using discursive social psychological research approach. The analysis concentrated on the use of the pronouns “I”, “we” and “them”. The results were then analyzed in relation to theories on discursive membership and discursive communities (I). Individual semi-structured interviews with team members (n=18) from four of the six teams were carried out using critical incident techniques. The interviews were analysed via latent qualitative content analysis and the results were interpreted in the light of theories on sociology of professions and learning at work (II).The findings showed that two discursive patterns emerged in the team members’ constructions of “we the team”. These patterns were designated knowledge synergy and trustful support (I). The following three themes that touched upon the difficulties of interprofessional teamwork were identified in the personal interviews: (A) difficulties concerning the teams’ dynamics that arose when the team members acted as representatives for their respective professions; (B) difficulties when the various contributions of knowledge interacted in the team; and (C) difficulties that were related to the surrounding organisation’s influence on the team (II).The conclusion was reached that the discursive pattern provided rhetorical resources for the team members, both in order to reaffirm membership in the team and to promote their views with other care providers, but also to deal with difficulties regarding, for example, lack of unity in outlook. The conclusion was also drawn that, in addition to the individual consequences, one outcome of the perceived difficulties was that they caused limitations of the use of collaborative resources to arrive at a holistic view of the patient’s problems. Thus the patients could not be met in the desired manner.The practical implications of the research project concern the development of teams in which various forms of interprofessional learning can influence the continued development of the team and the management of health care in regard to the importance of implementation processes and organisational learning.
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| 48. |
- Lanemo Myhrinder, Anna, 1975-
(författare)
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Restricted antigen recognition in B cell chronic lymphocytic leukemia
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic lymphocytic leukemia (CLL) cells are considered to be derived from antigen-exposed B cells. To further explore the antigen-driven selection behind the leukemogenesis of CLL, we performed immunoglobulin (Ig) specificity screening of 7 CLL cell lines and 23 primary CLL clones from patient peripheral blood. We also included a recombinant monovalent monoclonal antibody (mAb) belonging to a subset of CLL cases with identical or semiidentical heavy chain complementarity determining region 3 (HCDR3) of the IGHV3-21 gene rearrangement. We found CLL mAb specificities against vimentin, filamin B, cofilin-1, proline-rich acidic protein 1, cardiolipin, oxidized low density lipoprotein and Streptococcus pneumoniae polysaccarides. These molecules are functionally associated with microbial infection and/or apoptotic cell removal. An antigen-driven selection would therefore imply that CLL B cell precursors are involved in the elimination and scavenging of pathogens and apoptotic cells, which could trigger the development of the disease.The limited in vitro survival of CLL cells makes Epstein-Barr virus (EBV) immortalization of CLL cells a useful experimental model for studies on antibody-specificity screening. Considering the intricate procedure of EBV transformation of CLL cells and the many false cell lines used worldwide, we also wanted to characterize and evaluate the authentic origin of several previously established CLL cell lines and their normal lymphoblastoid counterparts. Three of the CLL cell lines tested were truly authentic (I83-E95, CLL-HG3 and CII), two had features of a biclonal Ig expression (232B4 and WaC3CD5+), one was only tentatively verified (PGA-1), whereas one cell line could not be verified (EHEB) due to lack of original patient cells for comparison. Two of the presumed normal lymphoblastoid cell lines tested were shown to be a neoplastic CLL clone. This study emphasizes the importance of proper cell line authentication and we will continue to verify additional cell lines not yet proven authentic.In conclusion, we provide evidence for natural Ab production by CLL cells and suggest that these cells might be derived from B cell precursors involved in the innate immunity and, thus, providing a first-line-defence against pathogens and in elimination of apoptotic cells.
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| 49. |
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| 50. |
- Li, Wei, 1962-
(författare)
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Oxidative stress, macrophages, iron, and atherosclerosis
- 1997
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Macrophages have a great capacity to take up exogenous material, such as oxidatively modified low density lipoproteins (oxLDL) and different sources of iron containing structures. OxLDL is taken up into macrophage lysosomes by receptor-mediated endocytosis, but poorly degraded, resulting in foam-cell formation. The foam cell formation and the cytotoxicity of oxLDL to several arterial wall cells might contribute to atherogenesis. The iron sequestrated by macrophages could potentially become cytotoxic, particularly following intralysosomal accumulation of low-molecular weight iron in a redox-active form, and under conditions of oxidative stress. Following autophagocytosis, endogenous ferritin/apoferritin may serve as chelators of such lysosomal iron and counteract the occurrence of iron-mediated intra-lysosomal oxidative reactions.In the present study, we estimated the influence of oxLDL on lysosomal enzyme activity, lysosomal membrane stability, and the modulation of these cellular characteristics by high density lipoprotein (HDL) and vitamin E (vit-E). We also examined iron-stimulated ferritin synthesis, and the effects of exogenously added apoferritin on cells and lysosomal membrane stability following oxidative stress. Human monocyte-derived macrophages and J-774 cells were used in the study. The activities of the lysosomal enzymes, cathepsin-L and N-acetyl-ß-glucosarninidase (NAßGase), were biochemically assayed on cellular fractions. The lysosomal integrity was estimated by an acridine orange (AO) vital staining test as well as by immunocytochemical cathepsin-D demonstration. Cellular ferritin was assayed by ELISA, and lysosomal iron was demonstrated by autometallography and transmission electron microscopy.We found that the total activities of NAßGase and cathepsin-L were significantly decreased, whereas their relative cytosolic activities were enhanced after oxLDL-exposure. Labilization of the lysosomal membranes was further proven by a decreased lysosomal AO-uptake and a relocation to the cytosol of cathepsin-D. as estimated by light- and electron microscopic immunocytochemistry. HDL and vit-E diminished the cytotoxicity of oxLDL by decreasing the lysosomal damage. The synthesis and accumulation of ferritin in HMDM are responses to the iron-exposure, but ferritin is not efficient enough to protect the lysosomes from oxidative stress. Endocytosed apoferritin acts as a stabilizer of the acidic vacuolar compartment of iron-loaded macrophages.
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