<p>Abstract</p><p>Background: To have type 2 diabetes affects life situation and thus the experiences oflifestyle changes. Treatment of type 2 diabetes consists of adapting to new lifestyles and theirown involvement. Orem (2001) theory of self-care has been used as a kind of scientificfoundation. Aim: The purpose of this study is to describe the experiences of lifestyle changesin people with type 2 diabetes. Method: Systematic literature review of descriptive andinductive synthesis approach has been used. Results: The analysis resulted in three themes.The themes were lack of knowledge, knowledge of the needs and difficulties in complyingwith health recommendations. Fear of type 2 diabetes and its complications are dependent onlack of knowledge and people with type 2 diabetes have therefore difficulty in implementinglifestyle changes. Information, motivation and social support and self-confidence are onereason that people with type 2 diabetes can learn. Personal and family life factors, attitude ofhealth personnel, and breaking old patterns all lead to difficulties to follow healthrecommendations. Conclusion: People with type 2 diabetes experiencing deficiencies in careand these results in difficulties to perform lifestyle changes. Information given to people withtype 2 diabetes need to be more individualized, and that the hospitality of health professionalsshould be better.Keywords: experiences, lifestyle changes, support, type 2 diabetes.</p>

<p>Although Cerebral Palsy (CP) is a lifelong disability, the research has mainly focused in children with CP. However, in recent years new studies have examined the different aspects of being an adult with a congenital disability.</p><p>The overall aim of this thesis is to contribute to increased knowledge and understanding in living with cerebral palsy as an adult, with special focus on the lived body and physiotherapy/physical activity.</p><p>The thesis is based on two populations. The first population (study I) consists of 48 individuals with a variation in gross motor function equivalent to the general CP‐population, including all five levels according to a gross motor classification (Gross Motor Function Classification System, GMFCS). The second population (study II and III), consists of 22 individuals, representing level II to IV according to the gross motor classification (GMFCS).</p><p>Study I comprises structured questions and clinical investigations with well‐recognized assessment instruments and are analysed according to quantitative methods. Study II and III are based on in‐depth interviews and are analysed using qualitative methods.</p><p>The overall result is that there is a deterioration of motor function in many individuals already early in adulthood. These deteriorations are preceded and/or followed by musculoskeletal problems such as pain and limited range of motion, often in combination with fatigue. Despite deteriorations many people maintain daily personal activities, but are often forced to prioritize among societal activities.</p><p>The deterioration is often perceived as slow and imperceptible, but it also results in a change in self‐image with new thoughts about otherness and being different. This can be experienced in relation to activity limitations with difficulties in taking part in other people’s activities, but also in relation to attitudes and treatment from other people. The process of deterioration also influences autonomy, with limited ability to determine one’s own daily life.</p><p>Important prerequisites for carrying out physical activity in a longer perspective is that it has to be enjoyable, give effects, be comprehensible and integrated in daily life. In addition it is important with support from competent professionals in health care. Experiences of these prerequisites vary and, above all, in adulthood the lack of competent support is a factor which is illuminated of the majority of the interviewed and assessed individuals.</p>

<p><strong>Background:</strong><em><strong> </strong></em>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.</p><p><strong>Aims:</strong> 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.</p><p><strong>Subjects and methods:</strong> 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.</p><p><strong>Results:</strong> 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.</p><p><strong>Conclusions: </strong>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.</p>

<p>Cardiovascular diseases (CVDs) are the most common cause of death in Western countries. Smoking, hypertension, diabetes mellitus and hypercholesterolemia are considered as major risk factors. However, the underlying mechanisms by which these factors cause CVDs are not entirely clear. Angiotensin-converting enzyme (ACE) is a key enzyme in the renin-angiotensin-aldosterone system, converting angiotensin I to the vasoactive peptide angiotensin II. Besides being an important factor for normal regulation of blood pressure, ACE appears to be involved in the pathogenesis of atherosclerosis. Previous studies have shown an upregulation of ACE in atherosclerotic plaques. There is genetic polymorphism in the ACE gene (ACE I/D polymorphism) which is strongly connected to the levels of ACE in plasma, but has also been associated with higher risk for cardiovascular diseases. The aim of this thesis was to investigate ACE in vitro and in vivo, in relation to cardiovascular risk factors and CVDs. The results showed that nicotine and nicotine metabolites increase ACE activity in human endothelial cells in vitro. Smoking was associated with increased plasma ACE levels. This effect might be mediated by nicotine and nicotine metabolites. These results could explain one cellular mechanism by which smoking exerts negative effect on the vascular system. Extract of oral snuff inhibited ACE in human endothelial cells and in serum, whereas extract of cigarette smoke had no effect on endothelial ACE. If these results have any physiological relevance remains to be investigated. Cardiovascular risk factors and CVDs were associated with increased levels of ACE in plasma. No association between ACE D/D genotype and CVDs was found. Based on these results we suggest that an increased level of ACE, rather than ACE genotype, is associated with increased risk for CVDs.</p> / <p>Hjärtkärlsjukdomar är den vanligaste dödsorsaken i industriländer. Åderförkalkning är den bakomliggande process som orsakar hjärtkärlsjukdomar. En mängd olika riskfaktorer har identifierats (rökning, högt blodtryck, diabetes etc.) men man har inte helt lyckats kartlägga mekanismerna för hur dessa riskfaktorer leder till förkalkning av kärlen. Renin-angiotensin-aldosteron-systemet är ett av de viktigaste systemen i kroppen vad gäller reglering av blodtryck och vätske- och saltbalans. Angiotensin-converting enzyme (ACE) är ett nyckelenzym i reninangiotensin-aldosteron systemet och omvandlar angiotensin I till den aktiva peptiden angiotensin II. ACE är en central parameter för normal reglering av blodtryck, men man tror även att det är en viktig faktor för uppkomst av åderförkalkning. Tidigare studier har visat att individer med åderförkalkning har en ökad mängd ACE i det förkalkade området. Det finns en genetisk variation i genen för ACE som är starkt kopplad till mängd ACE i blodet. Ett antal studier har visat ett samband mellan denna genvariation och risken att drabbas av hjärtkärlsjukdomar, medan andra studier inte funnit detta samband. Syftet med denna avhandling var att undersöka ACE i relation till risk faktorer för hjärtkärlsjukdomar och förekomst av hjärtkärlsjukdomar. Resultaten visar att nikotin och levernedbrytningsprodukter av nikotin (nikotinmetaboliter) ökar aktiviteten av ACE i mänskliga endotelceller, den celltyp som täcker insidan av alla blodkärl. Dessutom visades att rökning resulterar i en ökad mängd ACE i blodet. Det är tänkbart att denna effekt orsakas av nikotin och nikotinmetaboliter och skulle kunna vara en mekanism för hur rökning ger upphov till hjärtkärlsjukdomar. Snus däremot minskade aktiviteten av ACE, medan cigarrettrök inte hade någon effekt. Dessutom visades att både riskfaktorer för hjärtkärlsjukdomar och förekomst av hjärtkärlsjukdomar resulterar i en ökad mängd ACE i blodet och vi föreslår att mängden ACE är en viktigare faktor än ACE-genvariant, vad gäller risken för att drabbas av hjärtkärlsjukdom.</p>

<p>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.</p><p>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.</p><p>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.</p>

<p>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.</p> / In the printed version the series number of this Licentiate thesis is 98. In the electronic version it has been corrected to 99.

<p>Denna licentiatavhandling består av tre delarbeten. Dessa tre arbeten handlar omsymtom som inte alltid kommer i fråga när det gäller gastroesofageal reflux.I det första arbetet var syftet att undersöka huruvida patienter medmagmunsbråck (hiatushernia) blev förbättrade med avseende på symtom somfelsväljning till larynx (MSL) och till näsan (MSN), samt heshet (H), som ettresultat av hiatusherniaoperation. Nittio patienter, som undersöktes före ochefter hiatusherniaoperation, fyllde i frågeformulär om H, MSL och MSN. Hos30% av patienterna förekom MSL och lika många hade MSN. Heshet fanns hos25% av patienterna före operation. Dessa symtom hade ett signifikant inbördessamband (p<0.008). Alla symtom minskade efter antirefluxkirurgi (p<0.001).Förbättringen var oberoende av patienternas vikt.</p><p>I det andra arbetet studerades huruvida felsväljning var en extralaryngeal orsaktill heshet och om det var någon skillnad i prevalensen för felsväljning ochheshet mellan patienter med hiatushernia med gastroesofageal refluxsjukdom(GERD) och patienter med hiatushernia utan patologisk gastroesofageal reflux(GER). Patientmaterialet bestod av 198 patienter, som befunnits ha hiatusherniavid undersökning med esofagusmanometri och pH-refluxtest och somkontrollgrupp 262 personer ur normalbefolkningen, vilka inte visade sig hahiatushernia vid endoskopi. Dessa grupper svarade på ett frågeformulärangående symtom på heshet, felsväljning och halsbränna. Jämförelsen mellanpatientgrupp och kontrollgrupp visade H hos 35% respektive 13%, MSL hos35% respektive 5%, MSN hos 22% respektive 1% och halsbränna hos 85%respektive 6% (p<0.001). Båda symtomen MSL och MSN var vanliga(p<0.0001). H och MSL hade inget inbördes förhållande. H och MSL var likavanligt i gruppen med GERD som i gruppen med GER. Slutsatsen blev att detfinns en predisponering för H och MSL hos patienter med hiatushernia, menorsakssambandet är oklart. Heshet verkar inte vara orsakat av GERD.</p>

<p>Blood and tissue velocities are measured and analysed in cardiac, vascular and other applications of diagnostic ultrasound. Errors in system performance might give invalid measurements.</p><p>We developed two moving string test targets (“Doppler phantoms”) to characterise ultrasound Doppler systems. These phantoms were initially used to measure such variables as sample volume dimensions, location of the sample volume, and the performance of the spectral analysis. Specific tests were done to detect errors in signal processing causing time delays and inaccurate velocity estimation.</p><p>Even time delays as short as 30 ms in cardiac motion pattern may have clinical relevance. These delays can be measured with echocardiography, by using techniques such as flow and tissue Doppler and M-mode together with external signals (e.g., ECG and phonocardiography). If one or more of these signals are delayed in relation to the other signals (asynchronous), an incorrect definition of cardiac time intervals can occur. To determine if this time delay in signal processing is a problem, we tested three commercial ultrasound systems. We used a digital ECG simulator and a Doppler string phantom to obtain test signals. We found time delays of up to 90 ms in one system, whereas delays were mostly short in the other two systems. Further, the time delays varied relative to system settings.</p><p>To determine the accuracy in velocity calibration, we tested the same three ultrasound systems using the Doppler phantom to obtain test signals for flow and tissue pulsed Doppler and for continuous wave Doppler. The ultrasound systems were tested with settings and transducers commonly used in cardiac applications. In two systems the observed errors were mostly close to zero, whereas one system systematically overestimated velocity by an average of 4.6%. The detected errors can be considered small in clinical applications but might be serious in certain research applications. It is important to know the velocity error of the used ultrasound system and to judge it in relation to the application in which it is used.</p>

<p>By using archetypes, it is possible to define how data are stored in the EHR,which facilitates querying for data.</p><p>The objective of this thesis is to investigate the possibility of connecting a decisionsupport system to archetype-based medical records by using the ArchetypeQuery Language (AQL) and the Semantic Web Rule Language (SWRL).</p><p>The result shows that, since SWRL is a logic language rather than a programminglanguage, built-ins are necessary to allow SWRL rules to function as programmingrules. Built-ins are SWRL modules that can be written in e.g. Java,which allows complex functions to be created.</p><p>The conclusion is that built-ins can be used to connect archetypes and SWRLrules by querying the archetype path with AQL. There are however several ruledesign factors to consider when using SWRL e.g. data location problems.</p>

<p><strong>Background:</strong> 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.</p><p><strong>Aims: </strong>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.</p><p><strong>Methods: </strong>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.</p><p>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions:</strong> 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.</p> / In the list of articles in the Thesis the title of article I is "Tissue blood flow responses to external pressure in the sacral region of elderly individuals". The correct title is "Existence of tissue blood flow in response to external pressure in the sacral region of elderly individuals - Evaluation of a prototype".