Crohns sjukdom är en kronisk inflammatorisk sjukdom som påverkar hela gastrointestinala kanalen, från mun ner till ändtarmen. Sjukdomen är progressiv och innefattar olika skov av symptom, som till exempel diarré, magont, rektalblödning, viktminskning, feber och trötthet. Den exakta patofysiologiska orsaken är ej klargjord, men tros bero på olika faktorer som till exempel genetiska faktorer, miljöfaktorer samt immunologiska faktorer. Det är känt att individer med inflammatorisk tarmsjukdom (IBD) uttrycker en större population av mastceller och eosinofiler i tarmsubmukosa, och kan orsaka diverse symptom. Histamin-4 receptorer är G-proteinkopplade receptorer som har en nyckelroll i att förmedla inflammatoriska svar, och spelar en roll i immuncellsmigration till inflammerade vävnader. Syftet med projektet är att studera uttrycket av histaminreceptorn H4 på eosinofiler och mastceller i inflammerad tarmvävnad från patienter med Crohns sjukdom. Det medverkade 16 patienter, varav 8 hade Crohns sjukdom, och 8 var friska kontrollpatienter som opererats för tarmcancer. Uttrycket av eosinofiler, mastceller och Histamin-4 receptorer studerades med hjälp av immunohistokemisk metod. Resultatet visar statistisk signifikanta skillnader mellan patient och kontrollgruppen när det kommer till eosinofiler och mastceller, med ett p-värde <0,05. Det uppvisades ingen signifikant skillnad mellan grupperna när det kom till icke inmärkta celler som uttrycker histamin-4 receptorer, eosinofiler som uttrycker receptorn samt mastceller som uttrycker receptorn. Sammanfattningsvis finns det ett behov att studera detta område igen, med större urval, och möjligtvis förbättrade metoder för att komma fram till säkerställda slutsatser. / Crohn's disease (CD) is a chronic inflammatory disease that affects the entire gastrointestinal tract, from the mouth down to the rectum. The disease is progressive and involves flare-ups of symptoms such as diarrhea, abdominal pain, rectal bleeding, weight loss, fever, and fatigue. The exact pathophysiological cause is unclear but is believed to be related to various factors, including genetic, environmental, and immunological factors. It is known that individuals with inflammatory bowel disease (IBD) express a higher population of mast cells and eosinophils in the intestinal submucosa, which can cause diverse symptoms. Histamine-4 receptors are G-protein-coupled receptors that play a key role in mediating inflammatory responses and are involved in immune cell migration to inflamed tissues. The aim of the project is to study the expression of the histamine receptor H4 on eosinophil granulocytes and mast cells in inflamed intestinal tissue from patients with CD. Sixteen patients participated, including 8 with CD and 8 control patients who underwent surgery for colon cancer. The expression of eosinophils, mast cells, and histamine-4 receptors was studied using immunohistochemical methods. The results show statistically significant differences between the patient and control groups in terms of the number of eosinophils and mast cells, with a p-value <0.05. There was no significant difference between the groups in terms of un-stained cells expressing histamine-4 receptors, eosinophils and/or mast cells expressing the receptor. In conclusion, there is a need to further study this area with larger sample sizes and possibly improved methods to arrive at conclusive findings.

Type-2 diabetes has become a common disease. The complications associated with thedisease are often cardiovascular. Platelets are important components in hemostasis, one function is platelet adhesion. Platelet adhesion is the first step to form a platelet plug, together with subendothelial proteins. Blood lipids contribute to membrane structure of cells and has an important role in different signaling pathways. They have a key role in platelet activation and is associated with the changes in membrane lipids. C-reactive protein (CRP) is an acute phase protein and increases during inflammation. The physiological role is not fully known but increasing levels of CRP increases the risk for cardiovascular complications. The aim of this study was to analyze the correlation between platelet adhesion with blood lipids and high sensitivity CRP in type-2 diabetics. 69 patients with type-2 diabetes participated in this study. Lipids, CRP and platelet adhesion were analyzed, the values were used to perform correlation analysis. The results show statistically significant positive correlations between ApoA-1, HDL and platelet adhesion as well as significant negative correlations between LDL, ApoB/ApoA-1-ratio, LDL/HDL-ratio and platelet adhesion. ApoA-1 and platelet adhesion with collagen showed statistically significant correlations with r-values 0,299-0,436. ApoA-1/ApoB-quota showed statistically significant correlations with r-values from -0,492 to -0,268. Majority of correlations between totalcholesterol, ApoB, triglycerides, hsCRP and platelet adhesionshowed no statistically significant correlations. / Typ-2 diabetes har blivit en vanligare sjukdom. De komplikationer som kan uppstå vid diabetes, särskilt obehandlad diabetes, är ofta kardiovaskulära komplikationer. Trombocyter är viktiga komponenter i hemostasen, en av deras funktioner är trombocytadhesion. Trombocytadhesionen är första steget vid bildandet av en trombocytpropp, tillsammans med subendoteliala proteiner så kan trombocyterna fästa till kärlväggen och hemostasen påbörjas. Blodlipider bidrar till cellmembraners struktur, energiförvaring och har en viktig roll vid olika typer av signalering. De har en nyckelroll vid trombocytaktivering eftersom trombocytaktivering är associerad med förändringar som sker hos membranlipiderna. C-reaktivt protein (CRP) är ett akutfasprotein och ökar vid inflammation. Fysiologiska rollen är inte helt känd men stegring av CRP ökar risken för kardiovaskulära komplikationer. Syftet med denna studie är att analysera korrelationen mellan trombocytadhesion med blodlipider och högkänsligt CRP hos typ 2 diabetiker. Det medverkade 69 patienter med typ-2 diabetes i studien. Blodlipider, högkänsligt CRP och trombocytadhesion analyserades ochvärdena för respektive analyt användes för korrelationsanalyser.Resultaten visar statistiskt signifikanta positiva korrelationer mellan ApoA-1, HDL och trombocytadhesion samt signifikanta negativa korrelationer mellan LDL, ApoB/ApoA-1-kvot, LDL/HDL-kvot och trombocytadhesion. ApoA-1 och trombocytadhesion med kollagen som proteinyta uppvisade statistiskt signifikanta korrelationsintervall med r-värden på 0,299-0,436. ApoA-1/ApoB-kvoten visade statistiskt signifikanta korrelationsintervall med r-värdenmellan -0,492 till -0,268. Majoriteten av korrelationerna för variablerna: totalkolesterol, ApoB, triglycerider, högkänsligt CRP och trombocytadhesion visade inga statistiskt signifikanta korrelationer.

Standardbikarbonat innebär koncentrationen bikarbonat i plasmadelen av helblod under standardiserade förhållanden. Analysen baseras på uppmätta värden av partialtryck för koldioxid (CO2), pH, syrgasmättnad och total-hemoglobin samt en beräkning. Bikarbonat (HCO3-) har tillsammans med CO2 en central roll i syra-basregleringen där njurarna kan styra HCO3--koncentrationen och lungorna kan styra CO2-koncentrationen. Indikationer på att analysera standardbikarbonat är exempelvis misstanke om acidos eller alkalos samt hos personer med njur- och eller lungsjukdom. Syftet med examensarbetet var att studera den preanalytiska hållbarheten för vB-Standardbikarbonat för att om möjligt förlänga tiden till analys inom region Kalmar län. Analysen genomfördes på blodgasinstrumentet ABL 825 FLEX. Provmaterialet bestod av venöst helblod i mörkblå Natrium-heparin-rör från 68 blodgivare och 7 dialyspatienter. De provrör som förvarades i kylskåpstemperatur (+2 till +8 °C) analyserades efter 0, 2, 3, 4 och 5 timmars förvaring. De provrör som förvarades i rumstemperatur (+18 till +25 °C) analyserades efter 0, 1, 2, 3 och 5 timmars förvaring. Resultatet visade att hållbarheten var bättre vid förvaring i kylskåpstemperatur än vid förvaring i rumstemperatur. Vid förvaring i kylskåpstemperatur erhölls en genomsnittlig förändring på -0,14 mmol/L (-0,6 %), -0,44 mmol/L (-1,8 %), - 0,45 mmol/L (-1,8 %), -0,58 mmol/L (-2,4 %) vid respektive förvaringstid 2, 3, 4 och 5 timmar. Vid förvaring i rumstemperatur erhölls en genomsnittlig förändring på -0,36 mmol/L (-1,5 %), -0,65 mmol/L (-2,7 %), -0,98 mmol/L (-4,0 %), -1,57 mmol/L (-6,4 %) vid respektive förvaringstid 1, 2, 3 och 5 timmar. Efter genomgång av resultatet med medicinskt ansvariga läkare framkom det att två timmars förvaring i rumstemperatur och fem timmars förvaring i kylskåpstemperatur var godtagbara förvaringstider. Utifrån resultatet i denna studie föreslås därför en uppdatering av hållbarheten på analysen vB-Standardbikarbonat till två timmar i rumstemperatur och fem timmar i kylskåpstemperatur inom region Kalmar län. / Standard bicarbonate is the measured concentration of bicarbonate in the plasma-part of whole-blood under standardized conditions. The analysis is based on measurement of partial pressure of carbon dioxide, pH, oxygen saturation, and total hemoglobin as well as a calculation. Bicarbonate (HCO3-) and CO2 are particularly important components of the acid-base-regulation through the kidneys’ ability to manage the HCO3--concentration and the lungs’ ability to manage the CO2-conentration. Analysis of standard bicarbonate is indicated by, for example, a clinical suspicion of acidosis or alkalosis and in patients with renal- and or pulmonary-disease. The aim of this study was to evaluate the time from sampling to analysis regarding the analysis of vB-standard bicarbonate and if possible, upgrade the pre analytical handling within region Kalmar County. The analysis was performed with the blood gas-instrument ABL 825 FLEX. The sampling in this study consisted of venous whole-blood in dark blue sodium-heparin-test tubes from 68 blood donors and 7 dialysis patients. The test tubes were either placed at refrigerator-temperature (+2 to +8 °C) or at room-temperature (+18 to +25 °C). Test tubes stored at refrigerator-temperature were stored for 0, 2, 3, 4 and 5 hours before analysis and the test tubes stored at room-temperature were stored for 0, 1, 2, 3 and 5 hours before analysis. The results show that storage at refrigerator-temperature was better in comparison to storage at room-temperature. The mean change at refrigerator-temperature was -0,14 mmol/L (-0,6 %), -0,44 mmol/L (-1,8 %), - 0,45 mmol/L (-1,8 %), -0,58 mmol/L (-2,4 %) for each storage time 2, 3, 4 and 5 hours respectively. The mean change at room-temperature was -0,36 mmol/L (-1,5 %), -0,65 mmol/L (-2,7 %), -0,98 mmol/L (-4,0 %), -1,57 mmol/L (-6,4 %) for each storage time 1, 2, 3 and 5 hours respectively. After conversation with the medically responsible doctor about the acceptable storage time, the conclusion was that two hours at room-temperature and five hours at refrigerator-temperature were acceptable storage times. Therefore, based on the results of this study, a proposal was made to change the time of storage to two hours at room-temperature and five hours at refrigerator-temperature regarding the analysis vB-standard bicarbonate in region Kalmar County.

Anti-Müllerskt Hormon (AMH) är ett glykoprotein som spelar en avgörande roll för rätt behandling av patienter med fertilitetsproblem och diagnos av könsutvecklingsstörningar hos barn. Att utföra en verifiering av analys för AMH på sjukhuslaboratoriet i Värnamo, är av högsta relevans då analysen för närvarande inte utförs i region Jönköpings län. Repeterbarheten bedömdes genom 10 mätningar, medan total precision utvärderades med 4 dagliga mätningar under 5 dagar. Både repeterbarhet och total precision bedömdes med interna kontroller. Riktigheten inkluderade 22 patientprover från Linköping med varierande AMH-koncentrationer. Variationskoefficienten visade en mycket låg spridning kring medelvärdet för både repeterbarhet (1,22% och 0,75%) och total precision (1,39% och 1,12%). Resultatet på riktigheten visade ingen signifikant skillnad med ett p-värde på 0,061, vilket indikerar hög tillförlitlighet för klinisk användning och bidrar till att förbättra patientvården samt effektiviteten i behandlingen. Framtida studier kan dra nytta av att inkludera fler patientprover för att ytterligare utvärdera observerade skillnader.

Aim: To study the possibility of detecting lymph node metastasis in locally advanced urinary bladder cancer (UBC) treated with radical cystectomy (RC) by using preoperative positron emission tomography/computed tomography (PET/CT) and peroperative sentinel node biopsy (SNB) technique. We also investigate the clinical significance of macrophage traits expression by cancer cells, M2-macrophage infiltration (MI) in tumor stroma and the immunohistochemical expression of biomarkers in cancer cells in relation to clinicopathologic data. Patients and Methods: We studied prospectively 122 patients with UBC, pathological stage pT1–pT4 treated with RC and pelvic lymph node dissection (PLND) during 2005–2011 at the Department of Urology, Linköping University Hospital. In the first study, we compared the results of preoperative PET/CT and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes (LNs). In the second study we investigated the value of SNB technique for detecting pathological LNs during RC in patients with UBC. W also examined the significance of the primary tumor location in the bladder in predicting the site of LN metastases, and the prognostic significance of lympho-vascular invasion (LVI) and lymph node metastasis density (LNMD) on survival. In the third study, we investigate the clinical significance of macrophage infiltration (MI) in tumor stroma and macrophage-traits expression by tumor cells. In the fourth study, we investigate the cell cycle suppression proteins p53, p21, pRb, p16, p14 ARF as well as tumors proliferative protein Ki67 and DNA repair protein ERCC1 expression in cancer cells. The results were compared with clinical and pathological characteristics and outcome. Results: Prior to RC, PET/CT was used to detect LN metastasis in 54 patients. PET/CT had 41% sensitivity, 86% specificity, 58% PPV, and 76% NPV, whereas the corresponding figures for conventional CT were 41%, 89%, 64%, and 77%. SNB was performed during RC in 103 patients. A median number of 29 (range 7–68) nodes per patient were examined. SNs were detected in 83 out of 103 patients (81%). The sensitivity and specificity for detecting metastatic disease by SNB varied among LN stations, with average values of 67% -90%. LNMD or ≥8% and LVI were significantly related to shorter survival. In 103 patients, MI was high in 33% of cases, while moderate and low infiltration occurred in 42% and 25% of tumors respectively. Patients with tumors containing high and moderate compared to low MI had low rate of LN metastases (P=0.06) and improved survival (P=0.06), although not at significant level. The expression of different tumor suppression proteins was altered in 47-91% of the patients. There were no significant association between cancer specific survival (CSS) and any of the studied biomarkers. In case of altered p14ARF, ERCC1 or p21, CSS was low in case of low p53 immunostaining but increased in case of p53 accumulation, although not at a significant level, indicating a possible protective effect of p53 accumulation in these cases. Conclusion: PET/ CT provided no improvement over conventional CT in detection and localization of regional LN metastases in bladder cancer. It is possible to detect the SN but the technique is not a reliable for perioperative localization of LN metastases; however, LVI and LNMD at a cut-off level of 8% had significant prognostic values. MI in the tumor microenvironment but not CD163 expression in tumor cells seems to be synergistic with the immune response against urinary bladder cancer. Our results further indicate that altered p53 might have protective effect on survival in case of altered p14ARF, p21, or ERCC1 indicating an interaction between these biomarkers.

Rectal cancer is one of the three most common malignancies in Sweden with an annual incidence of about 2000 cases. Current treatment consists of surgical resection of the rectum including the loco-regional lymph nodes in the mesorectum. In advanced cases, neoadjuvant chemo-radiotherapy (CRT) prior to the operative treatment reduces local recurrences and enables surgery. The neoadjuvant treatment can also eradicate the tumour completely, i.e. complete response. This research project was designed to investigate the effects of preoperative radiotherapy/ CRT and analyze methods to predict response to CRT. Study I investigated the expression of the FXYD-3 protein with immunohistochemistry in rectal cancer, with or without preoperative radiotherapy. The results from the total cohort showed that, strong FXYD-3 expression was correlated to infiltrative tumour growth (p = 0.02). In the radiotherapy group, strong FXYD-3 expression was related to an unfavourable prognosis (p = 0.02). Tumours with strong FXYD-3 expression had less tumour necrosis (p = 0.02) after radiotherapy. FXYD-3 expression in the primary tumour was increased compared to normal mucosa (p=0.008). We concluded that FXYD-3 expression was a prognostic factor in patients receiving preoperative radiotherapy for rectal cancer. Study II investigated FXYD-3 expression in tumours that developed local recurrences following surgery and compared this with expression in tumours that did not develop local recurrences. There was no difference in the expression of FXYD-3 between the group that developed local recurrences and the group that did not develop local recurrences. There was no difference in survival between those with strong or weak FXYD-3 expression. We concluded that this study could not confirm the findings from study 1 i.e. that FXYD-3 expression has prognostic significance in rectal cancer. Study III was a register-based study on the incidence and effects of complete response to neoadjuvant treatment. Eight per cent of the patients with adequate CRT to achieve complete response also had a complete histological response of the luminal tumor in the resected bowel. Sixteen per cent of that group had remaining lymph node metastases in the operative specimen. Chemotherapy together with radiotherapy doubled the chance of complete response in the luminal tumour. Patients with remaining lymph node metastases had a lower survival rate compared to those without. We concluded that residual nodal involvement after neoadjuvant treatment was an important factor for reduced survival after complete response in the luminal tumour. Study IV followed up the results from the previous study by re-evaluating magnetic resonance imaging (MRI)- images in patients with complete tumour response. Two experienced MRI radiologists performed blinded re-staging of post CRT MR- images from patients with complete response in the luminal tumour. One group with lymph node metastases and another one without were studied and the results compared with the pathology reports. The sensitivity, specificity, and positive and negative predicted values for correct staging of positive lymph nodes was 37%, 84%, 70% and 57%. The size of the largest lymph node (4.5 mm, p=0.04) seemed to indicate presence of a tumour positive lymph node. We concluded that MRI couldn’t correctly stage patients for lymph node metastases in patients with complete response to CRT in the luminal tumour.

Kolesterol transporteras i blodet med hjälp av lipoproteinpartiklar. Höga nivåer av low-density lipoprotein (LDL)-kolesterol i blodet är en riskfaktor för kardiovaskulär sjukdom. Koncentrationen av LDL-kolesterol kan beräknas med hjälp av Friedewalds formel men det finns även metoder där LDL-kolesterol kan analyseras direkt. Syftet med arbetet var att verifiera metoden direkt LDL-kolesterol på analysinstrumentet Beckman Coulter AU680. Metodens inomserie- och totalimprecision analyserades. Två korrelationsstudier utfördes mellan direkt LDL-kolesterol och beräknat LDL-kolesterol, en med 43 patientprover med triglycerider < 4,5 mmol/L och en med 11 patientprover med triglycerider > 4,5 mmol/L. Friedewalds formel ska egentligen inte användas vid triglycerider > 4,5 mmol/L, men i detta fall användes formeln ändå för att utvärdera eventuella skillnader mellan metodernas resultat vid höga triglyceridkoncentrationer. Vid analys av metodens inomserieimprecision blev variationskoefficienten (CV) omkring 0,5 % vid analys av både den låga kontrollen (A1) och den höga kontrollen (A2). CV för totalimprecisionen blev 1,21 % vid analys av A1 och 1,11 % vid analys av A2. Korrelationsstudierna visade ett linjärt samband mellan metoderna men den direkta metoden gav något högre resultat vid lägre koncentrationer och något lägre resultat vid högre koncentrationer jämfört med beräknat LDL-kolesterol. Vid triglycerider > 4,5 mmol/L gav den direkta metoden betydligt högre resultat än beräknat LDL-kolesterol. Slutsatsen blev att metoden hade god precision. Överensstämmelsen mellan metodernas resultat var relativt bra för proverna med triglycerider < 4,5 mmol/L. Vid triglycerider > 4,5 mmol/L var differensen mellan metoderna stor, troligtvis på grund av falskt för låga resultat från beräknat LDL-kolesterol. / Cholesterol is transported in the blood by lipoproteins. High levels of low-density lipoprotein (LDL)-cholesterol in the blood is a risk factor for cardiovascular disease. The concentration of LDL-cholesterol can be calculated using the Friedewald formula but there are also methods that measure LDL-cholesterol directly. The aim of this study was to verify the method P-LDL-cholesterol on a Beckman Coulter AU680 analyzer. Within-run imprecision and total imprecision were analyzed. The correlation between direct LDL-cholesterol and calculated LDL-cholesterol was examined using 43 patient samples with triglyceride levels < 4,5 mmol/L and 11 patient samples with triglyceride levels > 4,5 mmol/L. The Friedewald formula is not supposed to be used on triglyceride levels > 4,5 mmol/L, but in this case the formula was used anyway to evaluate differences between the methods at high triglyceride concentrations. The coefficient of variation (CV) for the within-run imprecision was about 0,5 %, both for the low control (A1) and the high control (A2). Total imprecision had a CV of 1,21 % for A1 and 1,11 % for A2. There was a linear relationship between the methods, but the direct method gave slightly higher results at low concentrations and slightly lower results at high concentrations compared to calculated LDL-cholesterol. At triglyceride levels > 4,5 mmol/L the results from the direct method was considerably higher than calculated LDL-cholesterol. The conclusion is that the precision of the method was good. The correlation between the results from direct LDL-cholesterol and calculated LDL-cholesterol was relatively high for samples with triglyceride levels < 4,5 mmol/L. At triglyceride levels > 4,5 mmol/L there was a big difference between the methods, probably because of falsely low results from calculated LDL-cholesterol.

Snabb och korrekt artidentifiering är avgörande för effektiv behandling av svampinfektioner, särskilt bland immunsupprimerade patienter. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) används rutinmässigt på kliniska laboratorier för identifiering av karaktäristiska proteinmönster hos bakterier och jästsvampar genom tolkning av proteinspektra i en masspektradatabas för korrekt artidentifiering. Mögelsvamparnas hårda cellvägg och heterogena växtsätt med varierande proteinuttryck beroende på mognadsstadie, försvårar identifiering med MALDI-TOF MS. Metodens tänkbara fördelar mot traditionella metoden mikroskopering är förkortade svarstider, säkrare artidentifiering av fler arter och mindre beroende av subjektiv morfologisk bedömning. Studiens syfte var att undersöka om MALDI-TOF MS kunde anpassas och användas för identifieringen av mögelsvamp i klinisk rutindiagnostik. Fyra referensstammar (Aspergillus niger, A. fumigatus, A.terreus, A.flavus) och ett kliniskt isolat (A.terreus) undersöktes. Preparationsmetoderna (I) fullständig myrsyraextraktion, (II) direktapplicering och (III) suspension i destillerat vatten användes för analys av sporer och frontmycel hos yngre och äldre mögelkulturer. Två olika masspektradatabaser för artidentifiering jämfördes; rutindatabasen BDAL och den specialiserade mögeldatabasen Filamentous Fungi Library. Även plocktekniken av mögelmaterial inför analys med MALDI-TOF MS utvärderades. Vid vissa tillfällen förbättrades artidentifieringen efter extraktion av mögelkulturerna, medan i andra fall var direktapplicering fullt tillräcklig. Mögelmaterial med mycket sporer tenderade ge något fler artidentifieringar i BDAL oavsett kulturernas ålder.  Filamentous Fungi Library tenderade i vissa fall ge bättre resultat jämfört med BDAL för yngre kulturer. Fler studier krävs för att utvärdera och optimera MALDI-TOF MS som metod för artidentifiering av mögelsvamp. / Rapid and accurate species identification is crucial for successful treatment of fungal infections, especially among immunosuppressed patients. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is used routinely at clinical laboratories to identify characteristic protein patterns of bacteria and yeast by the interpretation of protein spectra in a database for accurate species identification. The hard cell wall of the mold and the heterogeneous growth with varying protein expression due to maturation, complicates identification with MALDI-TOF MS. The potential benefits of this method compared to microscopy as traditional method are shortened turn-around times, safer species identification of more species that is independent on subjective morphological assessment. The purpose of the study was to investigate whether MALDI-TOF MS could be adapted and used for the identification of molds in clinical routine diagnostics. Four reference strains (Aspergillus niger, A.fumigatus, A.terreus, A.flavus) and a clinical isolate (A.terreus) were examined. The preparation methods (I) complete formic acid extraction, (II) direct application and (III) suspension in distilled water were used for analysis of spores and frontmycelium from younger and older mold cultures. Two different masspektradatabases for species identification were compared; routine database BDAL and the specialized mold database, Filamentous Fungi Library. Also the collecting technique of mold prior to analysis with MALDI-TOF MS was evaluated. Sometimes, the species identification improved after extraction of mold cultures, while in other cases direct application was sufficient. Cultures with a lot of spores tended to give slightly more species identifications in BDAL regardless of the age of cultures. Filamentous Fungi Library, in some cases, tended to improve the performance compared to BDAL for younger cultures. More studies are required to evaluate and optimize MALDI-TOF MS as a method of mold identification.

Trigger finger is one of the most common hand conditions, with a prevalence of almost 3%. The aetiology remains unclear even though many causes have been suggested. The prevailing paradigm is that the pathogenesis of trigger finger is ascribed to primary changes in the first fibrous condensation of the tendon sheath (A1-pulley). Several studies have investigated pathology in the pulley, but few have investigated the tendon. The general aim of this thesis was to find out if there is pathology in the trigger finger tendon and to define it. We first looked at trigger finger tendon biopsies in a light microscope, and found that they were histologically different from healthy tendons. They showed signs of micro-ruptures, collagen degradation, increased amounts of ground substance, both hyper- and hypo-cellular areas, round active cell nuclei and absence of inflammatory cells, all similar to tendinosis. The histological picture was further assessed by using a scoring system for Achilles tendinosis. The trigger finger tendons scored high, suggesting a similar histopathology. Next, we performed a quantitative real-time polymerase chain reaction (qPCR) on trigger finger tendons. We assessed the mRNA expression of 10 genes, which have been described to be differently expressed in Achilles tendinosis (collagen 1 and 3, versican, decorin, biglycan, aggrecan, MMP-2, MMP-3, ADAMTS-5, and TIMP-3). The overall expression pattern agreed with previous studies on Achilles tendinosis, suggesting that the cellular function in trigger finger tendons is disturbed in a similar way as in Achilles tendinosis. Recent experimental and observational research has suggested potential side effects of statin treatment on tendons, but firm evidence was lacking. We performed an epidemiological study on two large population-based cohorts. Statin use was found to increase the risk of both trigger finger and tendinosis in the shoulder and Achilles tendons, especially among men. This suggests a similar pathology in trigger finger and tendinosis. We have also studied the time to treatment effect after a single injection of glucocorticoid in trigger finger. Our results suggest that 60-80% of patients can expect resolution of the triggering within 14 days, and half of them within seven days. This result allows correct information to be given to the patient and proper planning of follow-ups. In conclusion, the pathology in trigger finger tendons is similar to tendinosis in other tendons.

Warfarin är ett läkemedel som används för att förhindra att högriskpatienter såsom de med förmaksflimmer får tromboembolism. Denna verkan uppnås genom att hämma de K-vitaminberoende faktorerna VII, X och protrombin och på så sätt minska blodets förmåga att koagulera. Att hitta rätt dosering av läkemedlet för warfarinbehandlade patienter har visat sig vara svårt eftersom det kräver regelbunden provtagning och påverkas av mat- och levnadsvanor. Det vanligaste sättet att mäta protrombinkomplexhalten är med venös plasma men det är även möjligt att använda sig av kapillär plasma. Helblod kan användas för mekaniska metoder som inte använder sig av optisk detektion. Fördelen är att helblod inte kräver centrifugering. Studiens syfte var att undersöka om det fanns en signifikant skillnad (p≤0,05) mellan helblod och plasma som används i den nuvarande metoden för kapillära prover och om det finns en skillnad i stabiliteten av dessa prov. Dubbla prover togs från 30 warfarinbehandlade patienter och 5 icke warfarinbehandlade individer. Ett av proven centrifugerades och analyserades på plasma, det andra analyserades på helblod. Resultaten visade att det fanns en signifikant skillnad (p≤0,05) mellan metoderna. Bland-Altman diagrammet visade att 95 % av helblodsproverna inte var högre än 0,25 INR och lägre än 0,14 INR. Detta har en låg klinisk inverkan. 4 Proverna förvarades i rumstemperatur i upp till 24 timmar och analyserades sedan om. Ingen förändring över 10 % kunde observeras i hållbarheten. Studien visade att trots att det finns en signifikant skillnad är det möjligt att ersätta den nuvarande metoden med plasma och använda helblod istället. / Warfarin is a drug used to prevent high-risk patients such as those with atrial fibrillation from thromboembolisms. This effect is achieved by suppressing vitamin-K dependent factors VII, X and prothrombin and therefore decreasing the bloods ability to clot. Finding the right dosage of the drug for warfarin treated patients has proven difficult, as it demands regular blood draws to monitor their prothrombin complex level, which is affected by dietary and living habits. The most common way to measure prothrombin complex levels is by using venous plasma but it is also possible to use capillary plasma. Whole blood can be used for mechanical methods, which don’t use optical detection. The benefit is that whole blood doesn’t require centrifugation. The aim of this study was to investigate if there was a significant difference (p≤0,05) between using whole blood and plasma which is the existing method for capillary sample and also if there is any differences between the stability of these samples. Double samples from 30 warfarin treated patients and 5 non-treated persons were taken. One of the samples were centrifuged and analyzed on plasma and the other analyzed on whole blood. The results showed that there was a significant difference (p≤0,05) between the methods. Bland-Altman plot comparison showed that 95 % of the whole blood samples would not be higher than 0,25 INR and lower than 0,14 INR. This has low clinical impact. The samples were stored at room temperature for up to 24 hours and reanalyzed. No changes over 10 % in INR values were observed. This study showed that even though there is a significant difference, it is possible to replace the existing method which using plasma with the whole blood instead.