<p>Aim</p><p>The aim of this study was to evaluate the effects of MotVikt´s obesity-treatment program on eight severely obese subjects, concerning Body Mass Index, Waist-Circumference and Weight after three and a half months and Sense of Coherence, Body Image and Self-experienced Health after three months. The question in focus was: Did MotVikt´s obesity-treatment program have any effects concerning the factors mentioned above?</p><p>Metod</p><p>Information was collected with questionnaires that were filled out by the eight subjects, three men and five women, who participated in MotVikt´s last round of treatment. Data concerning waist-circumference, weight and BMI were provided by MotVikt. The questionnaires that were used to get information about Sense of Coherence, Body Image and Self-Experienced health were SOC-29, BSQ and IQOLA SF-36.</p><p>Resultat</p><p>The average BMI in the group has decreased with 2,9 kg/m2, from 39,7 till 36,8. The waist-circumference has decreased with in average 10,7 cm. The average weight has decreased with 7,5 %. Seven of eight patients have a decreased Sense of Coherence. The average score has changed from 142 to 130. Five of eight patients have improved their Body Image. The average score has changed from 90 to 75. The questions concerning Self-experienced Health show an improvement.</p><p>Diskussion</p><p>The main reason for MotVikt´s obesity treatment program is to make the patients loose 5-10 % of their bodyweight. After half of the treatment-time, most of the participants have already achieved that. It is good to see that all of the patients have a lower waist-circumference and therefore less abdominal obesity. The risks of complications are higher when fat is located to the abdominal area, why this is seen as an important finding that comes with health benefits.</p><p>Seven out of eight patients have decreased their Sense of Coherence, which we see as the most surprising finding in this study. We can only guess what possible reasons may have caused the decrease. One reason may be that the patients are in a phase where they are re-evaluating their lives as a result of the lifestyle change they are going through.</p> / <p>Syfte och Frågeställning</p><p>Syftet med studien var att undersöka eventuella effekter av MotVikts behandlingsprogram på åtta svårt feta individer avseende BMI, midjemått och vikt efter tre och en halv månads behandling samt ”Känsla av sammanhang” (KASAM), kroppsuppfattning, självupplevd hälsa efter tre månader. Frågeställningen var därför: Har MotVikts behandlingsprogram haft några effekter på varje individ av¬seende ovan nämnda faktorer?</p><p>Metod</p><p>Datainsamlingen har utförts i form av en enkätstudie på de åtta individer, tre män och fem kvinnor, som deltagit i den senaste behandlingsomgången på MotVikt. Värden på midje¬¬¬mått, vikt och BMI har tillhandahållits av MotVikt. KASAM, kroppsuppfattning och självupplevd hälsa undersöktes med hjälp av frågeformulären SOC-29, BSQ samt IQOLA SF-36.</p><p>Resultat</p><p>Gruppens genomsnittliga BMI har sänkts med 2,9 kg/m2 från 39,7 till 36,8. Midjemåttet har minskat med i genomsnitt 10,7 cm. Vikten har sjunkit med i genomsnitt 7,5 %. Sju av åtta patienter har en sämre Känsla av sammanhang. Genomsnittsvärdet har sänkts från 142 till 130. Fem av åtta har en bättre kroppsuppfattning. Vid första mättillfället hade gruppen en genomsnittlig summa på 90 och vid andra mättillfället 75. På frågorna gällande självupplevd hälsa ses en generell förbättring.</p><p>Diskussion</p><p>Det huvudsakliga målet med MotVikts behandlingsprogram är att få patienterna att minska sin vikt med 5-10 % av sin kroppsvikt. Redan efter drygt halva behandlingstiden har de flesta av deltagarna i gruppen uppnått detta mål. Det är glädjande att se att alla patienterna har minskat sitt midjemått och därmed sin bukfetma. Som tidigare nämnts är det större risk att drabbas av följdsjukdomar om fettet är lokaliserat till buken. Därför ses detta som ett viktigt resultat som förbättrar hälsan.</p><p>Att sju av åtta patienters känsla av sammanhang har minskat anser vi är studiens mest överraskande resultat. Orsakerna till detta kan vi endast spekulera kring. En tänkbar anledning kan vara att de just i denna fas omvärderar sina liv som ett resultat av den livsstilsförändring de genomgår.</p>

<p>Syfte och frågeställningar: Syftet med denna uppsats var att med hjälp av intervjuer proble¬matisera hur metoden Hälsoprofilbedömning (HPB) kan vara ett hjälpmedel vid livsstilsförändring. Speciellt fokus har lagts på den betydelse den uppföljande Hälsoprofilbedömningen har för förändringsprocessen.</p><p>Följande frågor står i fokus för denna studie:</p><p>• Hur upplevs Hälsoprofilbedömningen?</p><p>• Vilken roll spelar hälsoprofilbedömaren för upplevelsen av Hälsoprofilbedömningen?</p><p>• Vilka effekter får Hälsoprofilbedömningen?</p><p>• Vilka förväntningar har en deltagare inför sin uppföljande Hälsoprofilbedömning?</p><p>• Vilka är de bakomliggande orsakerna till dessa förväntningar?</p><p>• På vilket sätt speglas beteendeförändringen i upplevelsen av Hälsoprofilbedömningen och hur påverkar det förväntningarna?</p><p>Metod: Denna C-uppsats bygger på sju stycken intervjuer, fyra män och tre kvinnor. Urvalet bestod av en åtgärdsgrupp på ett företag där totalt 91 stycken erhöll ett brev per e-post med inbjudan att deltaga i studien. En påminnelse skickades ut till kvinnorna i urvalet för att nå en jämnare könsfördelning. Intervjuerna genomfördes med en intervjuguide som grund och under samtalets gång ställdes följdfrågor. Intervjuerna transkriberades ordagrant till en skriven text som sedan analyserades med syfte att finna kate¬gorier och teman.</p><p>Resultat: I upplevelserna av HPB finns både positiva och negativa erfarenheter men som helhet kan man se en positiv inställning till HPB. Trots upplevda brister i engagemang hos vissa hälsoprofilbedömaren upplevs de av en majoritet som kunniga och professionella. Respondenterna ser antingen positiva eller förhåller sig neutrala till att få genomföra en ny HPB. Ett drag som flertalet har gemensamt är att de attraheras av de fysiologiska mätningarna.</p><p>Slutsats: HPB ses av respondenterna som en inspirationskälla och tankeväckare. Det går att se att HPB kan ha varit en bidragande faktor till att det har skett beteendeför¬ändringar hos flera av respondenterna. Förväntningarna inför uppföljande HPB påverkas av de tidigare upplevelserna och erfarenheterna av HPB.</p> / <p>Aim: With interviews describe how the method of HPB (a health profile) can be used as a help in lifestyle modification. Certain focus has been put to study the effect of the HPB followed up.</p><p>Following questions were the focus of the study:</p><p>• What is the experience of HPB?</p><p>• How does the conductor of HPB affect the experience of the HPB?</p><p>• What effects can HPB lead to?</p><p>• What expectations has a participant of the HPB followed up?</p><p>• Which are the latent causes to these expectations?</p><p>• In which way does the behaviour modification affect the experience of HPB and how does it affect the expectations?</p><p>Method: This study is based on seven interviews, four males and three females. The selected group was based on 91 persons from one corporation. They received an invitation to participate in the study by e-mail. A reminder was sent to the females in the selection in order to reach a more equal setting of gender. The interviews where based on an interview guide and followed up with open questions during the conversations. The interviews where transcribed word by word to a written text and then analysed in order to find categories and themes.</p><p>Results: Both positive and negative experiences of the HPB were shown but in it entirety a mainly positive attitude towards the HPB can be seen. In spite of some cases of experienced lack of commitment from the conductor of the HPB the majorities experience that the conductors are well-informed and professional. The respondents are either positive or neutral to attend another HPB. There is an attraction for physical measurements in common by the respondents.</p><p>Conclusions: The respondents experience HPB to be suggestive and inspirational. It is possible to see that HPB has been contributing to the behaviour modification for many of the respondents. The expectations of the follow-up HPB is influenced by the previous experiences of HPB.</p>

<p>Syfte</p><p>I dokument om hälsa uttrycks ofta att alla har rätt till lika hälsa. Då det skiljer sig för hur varje individ ser på hälsa och vad som är viktigt i deras liv är syftet med denna uppsats att försöka problematisera hälsa, genom att beskriva och analysera fem kvinnors berättelser. Hur talar dessa kvinnor om hälsa i intervjuer, inom kategorierna ”kropp”, ”själ” och ”lust och last”. Vad är viktigt för kvinnorna för att må bra?</p><p>Metod</p><p>Studien består av en kvalitativ undersökning där fem kvinnor, boende i Stockholm, har intervjuats. Intervjuerna skedde i samtal och till hjälp fanns ett papper med förberedda teman. Dessa var sjukdom, arbete, familj, tid, stress, relationer, kost, kropp och motion. Kvinnorna lade själva till fyra teman; humor, rökning/droger, resor och musik. Intervjuerna har transkriberats för att därefter analyseras med hjälp av bland annat Antonovskys teori, KASAM, och Karaseks och Theorells krav-kontroll-stöd-modell.</p><p>Resultat</p><p>Kvinnorna anser att det måste finnas en balans och att mycket hänger ihop i livet, vilket liknar KASAM och krav-kontroll-stöd-modellen i vilka alla komponenter påverkar varandra. Kvinnorna är relativt överens, med vissa undantag. Faktorer som de anser är viktiga för hälsa och för att de ska må bra är bland annat en bra relation med familj och vänner då detta blir deras trygghet i livet. Kvinnorna talar också om att stress uppkommer då det är brist på tid och att det är viktigt att ha tid för sig själv, vilket de får mer när barnen blir större. Arbetet måste vara meningsfullt och stimulerande. De tycker också att det är viktigt att röra på sig och dessutom se till att äta bra. Utöver detta är det viktigt att ha humor, ej röka, ha möjlighet att resa och lyssna på musik som berikar ens liv. Dessa fem kvinnor har olika sätt att hantera saker de tycker är jobbiga, bland annat att motionera och vara ute.</p><p>Slutsats</p><p>Det finns många olika aspekter som är viktiga för dessa kvinnor och de skiljer sig endast lite mellan dem. Det är både fysiska och psyksiska aspekter som är viktiga för kvinnorna. I stort sett handlar allt om att ha en balans i livet. Saker som är viktiga för dem måste fungera och gör de inte det så mår kvinnorna mindre bra.</p> / <p>Aim</p><p>In documents about health, it is often said that everyone has the right to equal health. When there is a difference in the way every individual see health and what is important in their lives, the aim of this paper is to problemize health, by describing and analysing women’s stories. How do these women talk about health in interviews, in the categories “body”, “soul” and “lust and vice”. What is important for the women to feel well?</p><p>Method</p><p>The study consists of a qualitative research where five women, living in Stockholm, have been interviewed. The interviews were like a conversation and for help there was a paper with prepared themes. These were illness, work, family, time, stress, relationships, diet, body and exercise. The women themselves added the four themes humour, smoking/drugs, travels and music. The interviews have been transcribed in order to be analysed with the help of, for exampel, Antonovsky’s theory, KASAM, and Karasek’s and Theorell’s demand-control-support-model.</p><p>Results</p><p>The women think that there has to be a balance in life and that there is a link between different aspects of life, which is like KASAM and demand-control-support-model where all components influence each other. On the whole the women agree. Things they consider important for health and well-being are to have a good relationship with family and friends. This becomes their security in life. The women also talk about stress which occurs when there is a lack of time and that time to themselves is important, which occurs when the kids grown up. Work has to be meaningful and stimulating. They also think that it is important to exercise and to eat well. A part from this it is important to have a sense of humour, not to smoke, have the opportunity to travel and listen to music which enriches their lives. These five women have different ways of coping trying situations, for example exercise and be outdoors.</p><p>Conclusions</p><p>There are many different aspects that are important to these women and they don’t differ much. Both physical and mental aspects are important. Above all, it is about having a balance in life between different components. The things that matter most for these women have to function well in order for them to feel well.</p>

<p>Syfte: Syftet med uppsatsen var att göra en analys av vilka resultat som deltagarna uppnått efter 2 års dagvårdsbehandling på Överviktsenheten, Karolinska Universitetssjukhuset. Följande frågor står i fokus för denna studie:</p><p>• Svarar män och kvinnor olika på behandlingen i fråga om relativ och absolut viktminskning?</p><p>• Finns det skillnader mellan ursprungs-BMI (kg/m2) och viktminskningen, i relativa och absoluta termer?</p><p>• Skiljer sig olika åldersgrupper åt i fråga om relativ och absolut viktminskning?</p><p>• Hur ändras sjukdomsprevalensen för IGT/diabetes typ II, höga triglyceridnivåer, hypertoni och metabolt syndrom under behandlingens gång?</p><p>Metod: Behandlingen innefattar beteendemodifikation i form av förändrade kostvanor och ökad fysisk aktivitet. Uträkningarna baseras på tre mätningar; före behandlingsstart, samt efter 1 och 2 år. Dessa består av blodprover samt längd, vikt och blodtryck. Deltagarna har delats in i kön-, ålder- och BMI-grupper och effekterna presenteras i form av relativ samt absolut viktminskning. För behandlingseffekter utifrån följdsjukdomar har fokus varit sjukdom vs. icke sjukdom. Värdena presenteras som medelvärden och standardavvikelse/95 % konfidens-intervall. ITT, intention-to-treat förfarande, har använts och det senast uppmätta värdet har därför lagts in när data saknas. Parametriska tester har genomgående använts.</p><p>Resultat: Det föreligger ingen signifikant könsskillnad ifråga om viktminskning. De deltagare med ett högre BMI vid start d.v.s. 40 (kg/m2) har en signifikant större viktminskning (relativ och absolut) än de deltagare med lägre BMI vid start (<35). Det föreligger ingen signifikant skillnad mellan de olika ålderskategoriernas viktminskning. Förändringar av sjukdoms-prevalensen visades mellan 0-1 år. Till exempel var den relativa fördelningen av metabolt syndrom 70% vid behandlingsstart och 55% efter 1 år för männen.</p><p>Slutsats: Viktminskningen påverkades inte av vare sig kön eller ålder, dock av nivån på BMI. Viktminskning förekom i samtliga kategorier (kön, BMI och ålder) mellan år 0-1. Dock förekom det en viss viktökning mellan 1-2 år.</p> / <p>Aim: To describe the effects of a 2-year long, lifestyle modification obesity treatment programme at the Obesity unit, Karolinska University hospital. The following questions were the focus of the study:</p><p>• Are there differences between men and women in terms of relative and absolute weight loss?</p><p>• Are there differences between level of obesity (calculated from BMI) and relative and absolute weight loss?</p><p>• Are there any differences between different age groups and relative and absolute weight loss?</p><p>• To what extent, if any, does the programme influence the prevalence of IGT/diabetes type II, high levels of triglycerides, hypertension and metabolic syndrome?</p><p>Method: The programme focuses on lifestyle changes (diet and physical activity). The analyses are based on data before the treatment started and after 1 and 2 years. The measures include blood samples, height, weight and blood pressure. The patients were divided into different categories based on sex, age and level of obesity (BMI) and the results are presented as relative and absolute weight loss. For effects on related morbidity, the focus was on transition between illnesses vs. no illness. ITT, intention-to-treat, is used and the latest observed value has been used when data was missing. Parametric statistics were used.</p><p>Results: There was no significant sex difference in weight loss. Patients with a higher BMI i.e. 40 (kg/m2) at start of treatment achieved a greater weight loss, than patients with a smaller BMI value (<35) at start. There were no significant differences between different age-categories, in terms of weight loss. Disease transitions were showed between start of treatment and year 1. For example, the prevalence of the metabolic syndrome was 70% at start of treatment for men and 55% after 1 year.</p><p>Conclusion: Sex and age did not affect weight loss, whereas BMI did. Weight loss occurred between year 0 and year 1, in all categories (sex, age, BMI), whereas weight tended to increase between year 1 and 2.</p>

<p>Syfte och frågeställningar</p><p>Syftet med den här studien har varit att fördjupa mina egna kunskaper om skador på främre korsbandet i knäleden samt att ta reda på hur skador å korsbandet vanligtvis behandlas. Dessutom ville jag få svar på vilken typ av rehabiliteringsåtgärder som anses vara bäst idag.</p><p>Metod</p><p>Arbetet utgörs av en litteraturstudie där fakta inhämtats i faktaböcker om idrottsskador samt en mängd vetenskapliga artiklar.</p><p>Resultat</p><p>En främre korsbandsskada är vanligt framför allt inom vissa bollsporter med pivoterande moment som t.ex. fotboll och handboll. Även inom utförsåkning och ishockey förekommer korsbandsskador. De uppkommer oftast genom att idrottsutövaren fastnar i underlaget och vrider till i knäet. Det finns ett antal riskfaktorer som ökar risken för en skada, t.ex. den fysiska konditionen och styrkeobalans mellan muskelgrupper.</p><p>De flesta skador behandlas med en rekonstruktion av korsbandet och därefter följer en rehabiliteringsperiod på ca. sex månader. Tyvärr uppstår inte alltför sällan diverse komplikationer, som t.ex. quadricepssvaghet, extensionsbrist och patellofemorala smärtor. Detta är allvarligt eftersom alltför många inte återgår till sina idrotter.</p><p>Slutsats</p><p>Rehabiliteringen har gått framåt mycket de senaste 10 åren, men fortfarande måste den eller operationsmetoderna förbättras ytterligare för att få ett bättre resultat. Eftersom rehabiliteringen är lång och krävande bör stor vikt läggas på att motivera och pusha på patienten. Då blir oftast resultatet bättre. Man bör även arbeta för att förebygga att en främre korsbandsskada någonsin uppstår.</p> / Idrottslärarlinjen 1993-1995

Airway remodeling is a contributing cause to the pathological structural changes, such as increased cell proliferation, observed in asthma. Platelets have been found in autopsy lungmaterial obtained from asthmatic patients and are well known to induce proliferation in vitro of a variety of cells. However, the role of platelets in airway remodeling is far from understood. This thesis aims to clarify the involvement of platelets in fibroblast and airway smooth muscle cell (ASMC) proliferation in vitro and to elucidate the importance of HA, FAK, eicosanoid and ROS dependent signaling. The results demonstrate that platelets induce ASMC proliferation through NADPH-oxidase and 5-LOX dependent mechanisms. In addition, platelets also induce a 5-LOX dependent fibroblast proliferation. Furthermore, morphological analysis demonstrates that platelets bind to the extracellular matrix component HA through its receptor CD44 and thereby induce a FAK dependent ASMC proliferation. Taken together, the results obtained in this thesis suggest that platelet/HA interaction mediated through CD44 is of importance for platelets ability to induce cell proliferation. Moreover, the results propose that platelet-induced fibroblast proliferation is 5-LOX dependent and that platelets induce a HA, CD44, FAK, 5-LOX, and ROSdependent ASMC proliferation. This action of platelets represents a potential important and novel mechanism that may have an impact on the remodeling process and in the development of new pharmacological strategies in the treatment of inflammatory respiratory disease such as asthma.

The acute-phase protein α1-acid glycoprotein (AGP; orosomucoid) was initially identified andcharacterised in the 1950s. The normal plasma concentration is around 0.5-1 mg/ml butduring inflammation the concentration increase several fold and the carbohydrate compositionof the protein changes. AGP is a highly glycosylated protein with 45 % of the molecularweight consisting of glycans. These glycans are believed to be of importance for the functionof the protein. However, the precise physiological role of AGP is still unclear. The present thesis reveals that AGP at physiological concentration induce calcium elevationin human neutrophils and platelets. In neutrophils this response was enhanced several fold ifsurface L-selectin was pre-engaged. Our results showed that this L-selectin-mediatedamplification was abolished if the neutrophils were pre-treated with Src or phosphoinositide3-kinase (PI3K) inhibitors. AGP alone did not induce production of reactive oxygen species(ROS) in neutrophils. However, if the neutrophils were activated by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) a subsequent addition of AGP caused aprominent ROS response. Moreover, both the calcium rise and the ROS response weredepending on sialic acid residues on AGP. In the case of calcium elevation we defined thereceptor as sialic-acid-binding immunoglobulin-like lectin (Siglec)-5 on the neutrophil. In platelets, AGP induced a Rho-kinase dependent phosphorylation of myosin phosphatasetarget subunit-1 (MYPT1) and a minor calcium response. This resulted in a prominent plateletshape change (i.e. spherical shape and granule centralization) recorded as change in lighttransmission and by differential interference contrast (DIC) microscopy. The shape changecaused by AGP was strongly suppressed by inhibition of Rho-kinase and abolished by Rhokinaseinhibition combined with chelation of intracellular calcium. No other manifestations ofplatelet activation like aggregation or secretion were registered. Opposite to neutrophils theeffect of AGP on platelets was not mediated by an interaction between sialic acid and siglecmolecules. However, the results indicated that AGP may bind to a collagen/thrombospondin-1surface receptor. Endogenous inhibitors like nitric oxide (NO) and adenosine abolished theAGP-induced platelet shape change. The antagonizing action of NO on shape change causedby AGP was long acting. In comparison, other aspects of agonist-induced platelet activation(e.g. intracellular calcium elevations) are only transiently suppressed by NO. This indicatesthat endothelium-derived NO may play a crucial role to counter balance the effect of AGP in vivo. Take together the results in this thesis reveal that AGP can initiate intracellular signalling andmodulate functional responses in neutrophils and platelets.

The number of patients who are admitted for in-hospital care in Sweden because of burns is about 12/100,000, and only a small proportion of these have larger burns. Among them, and particularly among those who die in hospital, a condition referred to as “organ dysfunction” is common and an important factor in morbidity and mortality. The fact that the time of the initial event is known, and the magnitude of the insult is quantifiable, makes the burned patient ideal to be studied. In this doctoral thesis organ dysfunction and mortality were studied in a descriptive, prospective, exploratory study (no interventions or control groups) in patients admitted consecutively to a national burn centre in Sweden. The respiratory dysfunction that is seen after burns was found to be equally often the result of acute respiratory distress syndrome and inhalation injury. We found little support for the idea that this early dysfunction is caused by pneumonia, ventilator-induced lung injury, or sepsis. Acute kidney injury (AKI) was also common, and mortality was associated with severity. Importantly, renal dysfunction recovered among the patients who survived. Pulmonary dysfunction and systemic inflammatory response syndrome developed before the onset of AKI. Sepsis was a possible aggravating factor for AKI in 48% of 31 patients; but we could find no support for the idea that late AKI was mainly associated with sepsis. We found that older age (over 60 years), greater TBSA%, and respiratory dysfunction were associated with increased mortality, but there was no association between the overall mortality and sex. We also found that early transient liver dysfunction was common, and recorded early hepatic “hyper”- function among many young adults. Persistent low values indicating severe liver dysfunction were found among patients who eventually died. We conclude from this investigation that overall organ dysfunction is an early and common phenomenon among patients with severe burns. Our data suggest that the prognosis of organ dysfunction among these patients is good, and function recovers among most survivors. Multiple organ failure was, however, the main cause of death. The findings of the early onset in respiratory dysfunction and a delay in signs of sepsis are congruous with the gutlymphatic hypothesis for the development of organ dysfunction, and the idea of the lung as an inflammatory engine for its progression. We think that the early onset favours a syndrome in which organ dysfunction is induced by an inflammatory process mediated by the effect of the burn rather than being secondary to sepsis. Our data further suggest that clinical strategies to improve burn care further should be focused on early interventions, interesting examples of which include: selective decontamination of the gastrointestinal tract to prevent translocation of gut-derived toxic and inflammatory factors; optimisation of fluid replacement during the first 8 hours after injury by goal-directed resuscitation; and possible improvement in the fluid treatment given before admission.

Background and aims: Collagenous colitis (CC) is a diarrheal disorder with an incidence rate of 5-6/100000 inhabitants, affecting mainly middle-aged women. The diagnosis is made by histology of the colonic mucosa. Classical findings are a thickened subepithelial collagenous layer and chronic inflammation in the lamina propria. In inflammatory bowel disease (IBD) the mucosal barrier function is important in pathogenesis. The main purpose of the thesis was therefore to describe the barrier function in CC. The cause of CC is uncertain but the condition seems to be associated with bile acid malabsorption. Increased faecal bile acids are known to induce diarrhea. In functional studies the influence of bile acids on mucosal permeability in biopsies of healthy human individuals and in patients with CC was investigated. Methods and patients: In the first paper a single patient with intractable CC was examined before surgery, with loop-ileostomy and after bowel reconstruction. For the other studies a total of 25 patients with CC were included (20 women, 5 men, mean age 66 years). There were three groups (14 patients in clinical remission without medical treatment, 11 with active disease, and 8 of these again after 6 weeks of budesonide treatment); 17 individuals with normal histology served as controls. Endoscopic biopsies from the sigmoid colon were mounted in modified Ussing chambers and assessed for short-circuit current (Isc), transepithelial resistance (TER), and transmucosal passage of chemically killed E. coli K12 after addition of chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA). The biopsies were further investigated with confocal microscopy to assess bacterial transepithelial passage. Results: Para- and transcellular permeability was increased in active CC, but normalized with histological improvement due to faecal stream diversion. After bowel reconstruction, permeability to CrEDTA and HRP increased again. In CC, bacterial uptake in colonic biopsies was significantly higher in all groups than in controls. Despite significant alleviation of symptoms, budesonide did not normalize the increased bacterial passage. Histology was unchanged after 6 weeks of budesonide treatment. DCA augmented mucosal permeability to CrEDTA in a dose-dependent manner and even such a low dose as 100 μmol/l DCA increased bacterial uptake significantly. The combination of bile acids and E.coli K12 had additive effects on TER. 100 μmol/l CDCA and DCA increased bacterial uptake in biopsies of CC patients in remission 4-fold, but had no additive effect on biopsies from patients with active disease. Furthermore, patients in clinical remission on budesonide treatment showed no bile acidinduced effects on E.coli K12 passage. Conclusion: Collagenous colitis presents with increased para/transcellular permeability and bacterial uptake, irrespective of disease activity or budesonide treatment, signifying an underlying mucosal barrier defect. Faecal stream diversion can normalize the barrier dysfunction, but budesonide does not, despite its beneficial clinical effects which alleviate diarrhea or bowel symptoms. Bile acids in physiological concentrations have the potential to augment bacterial uptake, especially in mucosa from CC patients in remission. Budesonide treatment appears to counteract the bile acid induced mucosal impairment. These detrimental effects of bile acids on mucosal barrier function might facilitate initiation and perpetuation of mucosal inflammation in CC.

Background and aims. Crohn’s disease (CD) is a chronic inflammatory bowel disease (IBD) with potentially deleterious effects on well-being and daily-life functioning. A complete picture of health status in CD therefore comprises both disease activity (DA) and health-related quality of life (HRQL). Several measures of DA and HRQL in CD have been developed. Some have gained prominence as standard endpoints in clinical trials, but none has been validated in Swedish CD patients and their use in clinical practice has been limited. A conceptual health status model of five dimensions (Biological variables, Symptoms, Function, Worries, and Well-being) has been proposed for IBD health assessment, enabling the construction of the Short Health Scale (SHS), a four-item questionnaire intended to facilitate assessment and interpretation of HRQL in IBD. The aims of this thesis were: (1) to evaluate the Swedish versions of the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Rating Form of IBD Patient Concerns (RFIPC); (2) to evaluate the Short Health Scale; (3) to study the relationship between DA and HRQL variables by identifying determinants of DA outcome and by validating the SHS health status model; (4) to describe the spectrum of disease-related worries and repercussions on general HRQL in a context of social variables, sickness, and disability. Methods. The thesis is based on clinical variables and HRQL data measured in a population-based cohort of 505 CD patients, consecutively included in conjunction with their regular outpatient visits at three hospitals (Jönköping, Örebro, Linköping). The HRQL questionnaires were evaluated regarding construct validity, reliability, and responsiveness. Multivariate analyses were used to investigate the relationship between Crohn’s Disease Activity Index (CDAI) and physician-assessed DA. The SHS health status model was validated with structural equation modelling (SEM). Disease-related worries and concerns, general HRQL, social variables, sickness, and work disability were compared with data from background population or patients with ulcerative colitis (UC). Results. The IBDQ had good validity, reliability, and responsiveness, but the original dimensional structure was not supported. The RFIPC was valid, and reliable, but less sensitive to change in disease activity. The SHS had the highest completion rate and proved adequate psychometric properties. The CDAI correlated weakly with the physician’s appraisal of disease activity, being more influenced by subjective health perception than objective disease activity. SEM showed that the SHS model had a good fit to measured data, explaining &gt;98% of the covariance of the variables. Worries and general HRQL impairment were greater in CD than in UC, especially for women. Disease complications and impaired life achievements elicited most worries. CD patients had lower educational level. Female patients were more often living single. The rates of long-term sickness and disability were doubled compared with background population, with worse outcome for women. Conclusions. The IBDQ, the RFIPC, and the SHS all demonstrated adequate psychometric properties. The SHS was easier to administer and provided a more comprehensive picture of subjective health status. The weak correlation between CDAI and physician-assessed DA was explained by a strong influence of subjective variables on CDAI, stressing the importance of assessing DA and HRQL separately. The SHS health status model was further supported by SEM. CD has tangible effects on subjective health perception, worries and work capacity, especially for women.