| Abstract: | Natural transformation is recognaized as a major horizontal gene transfer mecahnism which impacts the genetic adaptaion , diversity and evolution of prokaryotes. Natural ransformation is uptake of extracellular DNA and its integration in a host genome. The fact that species take up foregin nucleotide sequences is believed to be followed by elimination of non-adventageous DNA sequence since bacterial genome do not grow in size.Transfer of gene from one species into the gene pool of another by backcrossing of hybid transformants with one parents is defined as intrgression. In this study the hypothesis that bacteria during introgrssion might regulate aquisition of foreign DNA by non-selected sequence by recombination was examined. The thesis contribute to earlier (Ray 2007)and ongoing projects investigating the fate of non-selected DNA during introgression of a choromsomal antibiotic resistance gene (nptII) in the bacterium A. baylyi. Hybrid transormants f A.baylyi ADP17021 contained a kanamycin resistance gene ande a mutS-gene deletion and an undeteramined amount of the donor strain A.sp.62A1. In this study DNA sequencing technologies and the Acinetobacter baylyi BD413 (ADP1) published geneome sequence was used to achive important results as identifying putative recombination junctions in ten back-transformants among the 10th and first generation and the effect of methyl-directet mismatch repair (mutS-deletion) on flanking DNA aquired by the recipient. The generation of the initial heterogamic transformation and ten subsequent backcross transformants were performed in a previous study (Ray, 2007). The aim of this study was identifying recombination junctins and the insert size of flanking DNA. It was clear that back-cross transformants harboured a significantly shorter donor sequence when compared to the initial genration. This indicates that during introgression, the non selected sequence will be gradually eliminated. |
| URI: | http://hdl.handle.net/10037/1569 |
| Abstract: | Til påvisning av selektive serotonin reopptakshemmere (SSRI) i sjøvann har det tidligere blitt benyttet ulike teknikker; væske-væske mikroekstraksjon (LPME) og tradisjonell fast faseekstraksjon (SPE). Disse metodene har vært begrenset av henholdsvis prøvevolum og tidkrevende ekstraksjon. Det har derfor vært et mål å utvikle en SPE-metode som er rask og effektiv, og som samtidig ved hjelp av store prøvevolum kan senke deteksjons- og kvantifikasjonsgrensene. Polymersorbentene XAD 2 og XAD 7HP har i et tradisjonelt SPE-oppsett blitt benyttet til å ekstrahere sjøvannsprøver med volum på 10 l. Prøvene ble analysert ved hjelp av UPLC-MS/MS. Innledende tester viste at XAD 7HP ga bedre gjenvinning enn XAD 2 og at begge sorbentene hadde gode fysiske egenskaper som tillot hurtig ekstraksjon av store prøvevolum. Ved oppskalering av sorbentmengde og prøvevolum kunne imidlertid ikke gode kromatografiresultater oppnås, og det ble konkludert med at dette mest trolig ble forårsaket av forurensninger fra sorbenten. Innenfor gitte tidsrammer har det derfor ikke vært mulig å utvikle en fungerende metode, og videre utvikling vil være nødvendig. Forutsatt utvikling av en effektiv metode for rensing av sorbentmaterialet vil metoden kunne være brukbar for både sure, nøytrale og basiske forbindelser fra sjøvann. |
| URI: | http://hdl.handle.net/10037/2213 |
| Abstract: | Masteroppgaven er en del av prosjektet ” Legemiddelgjennomgang ved utskriving fra St. Olavs hospital til sykehjem i Trondheim kommune”. Som har som mål å vinne praktisk kunnskap om og erfaring med en integrert intervensjon for legemiddelgjennomgang, overføring av legemiddelinformasjon og opplæring i legemiddelbruk for eldre pasienter som skrives ut fra St. Olavs hospital til sykehjem i Trondheim kommune. Formålet med masteroppgaven var å utarbeide en mal for pasientsamtalen, gjennomføre pasientsamtaler i rehabiliteringsinstitusjon og i hjemmet, og evaluere effekten av gitt legemiddelinformasjon på pasientens kunnskap om egen legemiddelbruk. Hensikten med pasientsamtalen er å oppnå at pasientene bruker legemidlene sine riktig når han/hun kommer tilbake i hjemmebasert omsorg. Resultatene fra denne studien tyder på at samtlige av pasientene kunne hatt behov for mer informasjon, og at flere av pasientene ønsket mer informasjon. Intervju med pasienter, pasientsamtaler og hjemmebesøk ser ut til å være nyttige tiltak, for å nå målet om riktig legemiddelbruk. |
| URI: | http://hdl.handle.net/10037/1647 |
| Abstract: | Gemcitabine, an anticancer agent, is currently in clinical use for the treatment of several types of cancer. Unfortunately, gemcitabine is rapidly metabolised with a short plasma half-life and its cytostatic action is strongly exposure-time dependent. In order to achieve the required concentration over sufficient periods of time, repeated application of relatively high doses is required. This, in turn, leads to dose-limiting systemic toxicity. In order to improve both the efficiency and the toxicity profile of gemcitabine the use of liposomes appears promising. In literature, only a few attempts to entrap gemcitabine within liposomes are found, however none of these liposomal formulations has reached clinical practice. In this study, an ammonium sulphate gradient was tried for active loading of gemcitabine into liposomes. Firstly, unsaturated egg phosphatidyl choline liposome dispersion was prepared with ammonium sulphate as hydration medium by the hand shaken method followed by filter extrusions with decreasing filter sizes down to 0.1 µm. Then, a transmembrane ammonium sulphate gradient was generated by removing extra-liposomal ammonium sulphate by size exclusion chromatography. Quantitative determination of the ammonium sulphate concentration, both outside and inside the liposomes, via electric conductivity measurement revealed that a gradient of external to internal ammonium sulphate of about 1:58 was achieved. Secondly, the liposomes were loaded with gemcitabine by incubation at different conditions. Among the loading conditions tested, a total loading time of 24 hours including heating for 2 hours at 60 ˚C seemed advantageous in achieving efficient loading. A higher starting concentration of gemcitabine resulted in enhanced loading efficiency, calculated on a molar basis. Comparing these results to a VPG passive loading technique, the active loading technique resulted in a gemcitabine:lipid ratio of about 1:20 versus 1:140 for the vesicular phospholipid gel loaded liposomes. Unfortunately, the actively loaded liposomes revealed poor storage stability with 80 % leakage after 24 hours. Further studies are needed in order to optimise loading and stability of the liposomes. |
| URI: | http://hdl.handle.net/10037/22 |
| Abstract: | S100A4 er et lite kalsiumbindende protein som tilhører S100-proteinfamilien. Proteinet er vist å ha en viktig rolle i metastaseprosessen, bl.a. ved å stimulere kreftcellenes motilitet og invasjonsevne. I de senere år har man blitt klar over at flere av de observerte biologiske effektene av S100A4 kan skyldes ekstracellulært protein. Ved transient transfeksjon med et reporterkonstrukt for transkripsjonsfaktoren NF-κB er det vist at ekstracellulær S100A4 øker aktiviteten av NF-κB i cellelinjen II-11b og at denne økningen skyldes økt aktivitet i den klassiske NF-κΒ signalveien. NF-κB spiller en sentral rolle i prosesser som inflammasjon, metastasering, apoptose og stimulering av proliferasjon, og sammenhengen mellom ekstracellulært S100A4 og aktivering av NF-κB er således interessant å studere videre. I denne oppgaven er S100A4-indusert NF-κB aktivering undersøkt i et utvalg humane kreftcellelinjer. Signifikant økning ble observert i fire av 15 undersøkte cellelinjer. Ved hjelp av mikromatriseanalyser av S100A4-behandlete osteosarkomceller er ephrin-A1 og optineurin identifisert som S100A4-induserte gener. I denne oppgaven er osteosarkomcellelinjen II-11b behandlet med rekombinant S100A4 og hemmere av den klassiske NF-κB signalveien. NF-κB-avhengig induksjon av ephrin-A1 og optineurin er vist med Western blot analyser og real-time RT-PCR. Videre er signaltransduksjonsmekanismer nødvendig for S100A4-indusert aktivering av NF- κB undersøkt ved bruk av rekombinant protein og hemmere av ulike intracellulære signalveier. Hemmere av følgende signaltransduksjonsveier/molekyler er undersøkt: serin/treonin kinaser, protein kinase C, G-protein koblede reseptorer, protein tyrosin kinaser, fosfatidylinositol-3-kinaser og fosfolipase C. Inhibering av serin/treonin kinaser med H-7 viste tydelig inhiberende effekt på aktivitet i NF-κB signalveien. Inhibering av protein tyrosin kinaser vha genistein viste en mulig inhiberende effekt på signalveien, men her er videre undersøkelser nødvendig for å trekke konklusjon. |
| URI: | http://hdl.handle.net/10037/1175 |
| Abstract: | Chronic myelogenous leukaemia is a monoclonal hematopoetic stem cell disorder characterised by the t(9;22) translocation and results in the constitutively activated Bcr-Abl tyrosine kinase. Since the tyrosine kinase activity of the Bcr-Abl fusion protein is the causative molecular event in CML, targeting the tyrosine kinase activity appears to be an attractive therapeutic strategy. Imatinib, Glivec, is a drug that inhibits the tyrosine kinase activity of Bcr-Abl. By binding to the ATP binding pocket, it prevents ATP from binding and the phosphorylation of downstream substrates is disrupted. Clinical studies have proven imatinib to be highly effective in the treatment of CML and imatinib is now the first-line therapy for all stages of CML However; point mutations have been detected in the ATP binding region of the Abl kinase domain. These mutations alter the conformation of the ATP binding pocket, disturb the binding of imatinib, and lead to imatinib resistance. We wanted to develop an experimental system where the effects of mutations in Bcr-Abl, leading to imatinib resistance, could be studied and new targets for therapy identified. For this we were going to clone Bcr-Abl into a pMACS 4-IRES.II vector. The Bcr-Abl gene is large, so to get the full-length construct, the cloning strategy involved ligation of PCR fragments in a stepwise order. Once inside the vector, the construct had to be transfected into BA/F3 cells. To study single point mutations some of the relevant point mutations were supposed to be subcloned into the Bcr-Abl construct and expressed in BA/F3 cells. To monitor the transfection and selection strategy with the pMACS 4-IRES.II vector and the BA/F3 cells, a pilot study was performed. A GFP gene was cloned into the pMACS 4-IRES.II vector and transfected into the BA/F3 cells. Expressed GFP will make fluorescent light that can be observed in a microscope. In conclusion, the cloning of this long Bcr-Abl gene proved to be more difficult than expected. First, misannealing resulted in an incomplete PCR product, which forced us to develop another strategy for this fragment. The 5’ part and the 3’part of Bcr-Abl was then successfully cloned in two vectors. However, all attempts to try to join the different Bcr-Abl fragments into one vector failed. |
| URI: | http://hdl.handle.net/10037/21 |
| Abstract: | Anabolic-androgenic steroids are naturally occurring or synthetic derivates of male sex hormones. All anabolic-androgenic steroids are prohibited by the World Anti-Doping Agency because of their muscle growth stimulating effect. At the Seibersdorf Doping-Control Laboratory, urine samples from athletes are first screened with a screen testing procedure to obtain an endogenous steroid profile, in order to identify samples suspected of containing endogenous steroids of exogenous origin. This is currently done using liquid-liquid extraction (LLE) followed by gas chromatography (GC) coupled with mass spectrometry (MS). It is desirable to perform the screening using GC- tandem mass spectrometry (MS/MS), and additionally optimise the extraction and the calibration curve conditions, to provide better specificity and selectivity. This thesis shows that the examined endogenous urine steroids can be quantified accurately using GC-MS/MS, the optimal hydrolysis condition include 2 hours with β-glucuronidase hydrolysis and water can be used as matrix for calibration curve samples. If the screen testing procedure indicates use of testosterone or any of its precursors, this needs to be confirmed using a confirmation procedure to accurately determine testosterone and epitestosterone concentrations, either as equivalents of their glucuronated metabolites, or by hydrolysing the glucuronides and measure free testosterone and epitestosterone. At the Seibersdorf Doping-Control Laboratory, confirmation is currently carried out using a time consuming LLE-GC-MS method. Solid phase extraction (SPE) – liquid chromatography- MS/MS would offer shorter extraction and analysis time, and the selectivity and sensitivity of MS/MS. A SPE-HPLC-MS/MS confirmation procedure, that simultaneously extracts and analyses testosterone, epitestosterone and their glucuronated metabolites, was developed. Through validation, the method was shown to provide good linearity, limit of detection, limit or quantification, intra- and intermediate precision, no matrix interference or carry over of substance from one sample to the next and high extraction recoveries for all substances. The method was tested using samples previously reported positive for elevated testosterone levels and different quality control samples. Measured testosterone/epitestosterone (T/E) – ratios were no further away from previously determined T/E – ratios than 10 %. Overall, the developed confirmation procedure proved to be a promising method for confirmation of elevated T/E – ratios. |
| URI: | http://hdl.handle.net/10037/2748 |
| Abstract: | Background: A previous study has shown that variations in threshold and intensity (lipid goal attainment) of statins for primary prevention contribute to regional differences in overall consumption of statins in Norway. Our objective was to explore how differences in prevalences of use, dosing characteristics, choice of statin and continuity of therapy in individual patients adds new information to previous results. Methods: Data were retrieved from The Norwegian Prescription Database. We included individuals from counties with high, average, and low statin consumption, who had at least one statin prescription dispensed during 2004 (N = 40 143). 1-year prevalence, prescribed daily dose (PDD), statin of choice, and continuity of therapy assessed by mean number of tablets per day. Results: The high-consumption county had higher prevalence of statin use in all age groups. Atorvastatin and simvastatin were dispensed in 79–87% of all statin users, and the proportion was significantly higher in the high-consumption county. The estimated PDDs were higher than the DDDs, up to twice the DDD for atorvastatin. The highconsumption county had the highest PDD for simvastatin (25.9 mg) and atorvastatin (21.9 mg), and more users received tablets in the upper range of available strengths. Continuity of therapy was similar in the three counties. Conclusion: Although differences in age-distribution seems to be an important source of variation in statin consumption, it cannot account for the total variation between counties in Norway. Variations in prevalences of use, and treatment intensity in terms of PDD and choice of statin also affect the total consumption. The results in this study seems to correspond to previous findings of more frequent statin use in primary prevention, and more statin users achieving lipid goal in the highest consuming county. |
| URI: | http://hdl.handle.net/10037/1388 |
| Abstract: | Gentamicin er hyppig brukt til å behandle alvorlige infeksjoner, men kan ved langvarig behandling eller ved høy serumkonsentrasjon gi vevsskade i både nyrer og ører. Måling av serumkonsentrasjonen skjer rutinemessig med en immunologisk metode som krever et blodvolum på 500 µl. Hyppige målinger er i noen tilfeller nødvendig for å få god kontroll på behandlingen. Premature barn har lav kroppsvekt og lite blodvolum, og et prøvevolum på 500 µl er for stort til at man kan ta hyppige prøver for å følge serumkonsentrasjon. Målet med studien var å utvikle en LC-MS basert analysemetode som vil kreve et mindre prøvevolum enn den immunologiske metoden. Prøvene ble opparbeidet med felling av proteiner med 10 % TCA. Deretter ble supernatanten overført til OSTRO-kolonne for å fjerne lipider før analyse med LC-MS. Kromatografien ble utført med en BEH AMIDE-kolonne En standardrekke med serumprøver i konsentrasjoner på 1, 4, 15, 30 og 50 µg/ml ble opparbeidet og analysert for validering av metoden. Det er utviklet en LC-MS metode for analyse av gentamicin basert på et prøvevolum på 25 µl serum. De fem ulike molekylene i gentamicin lot seg ikke fullstendig separere, men kunne kvantifiseres individuelt i det aktuelle konsentrasjonsområdet. Etter om lag 300 injeksjoner av prøve på var retensjonstid og form av gentamicin-toppene uendret. Metoden må videreutvikles for å innfri krav til linearitet, relativt standardavvik og nøyaktighet. |
| URI: | http://hdl.handle.net/10037/4328 |
| Abstract: | Legemidlet Plavix® (klopidogrel) er en blodplatehemmer som brukes i kombinasjon med acetylsalisylsyre (ASA) som profylakse etter stentimplantasjon for å hindre dannelsen av stenttrombose. Klopidogrel er et prodrug og krever hepatisk biotransformasjon for å utøve sin antiaggregerende effekt. Bruken av klopidogrel har økt betraktelig de siste årene. I 2004 ble klopidogrel brukt av 17973 individer i Norge, mens det i 2007 var 23283 brukere. Samtidig har man blitt klar over at det er variasjonen i grad av respons på behandlingen, og nonrespons (resistens) ser ut til å være et økende problem. Det overordnede formålet med denne oppgaven var å utvikle en metode for å identifisere non-respondere av klopidogrel. Målet var å utvikle en HPLC-MS/MS basert analysemetode for kvantitativ analyse av klopidogrel og dets metabolitter i serum. Det ble utviklet en HPLC-MS/MS metode som ga god kromatografisk separasjon av tiklopidin, N-7084 og klopidogrel. Det ble analysert vandige prøver av klopidogrel og tiklopidin, og det ble analysert serumprøver som var tilsatt klopidogrel, tiklopidin og internstandarden N-7084. Utfelling av proteiner i serum ble gjort med acetonitril og 10 % trikloreddiksyre i Milli-Q vann. Prøvene ble analysert direkte etter proteinutfelling, etter oppkonsentrering og etter fast-fase ekstraksjon hvor oppkonsentrering av prøver også ble utført. Metoden kan brukes til å måle klopidogrel, tiklopidin og metabolitter i serum, men det er nødvendig med videre optimalisering. Viktigst vil være å sikre en fullstendig utfelling av proteiner fra serum og utvikle en metode for analyse av klopidogrels inaktive karboksylsyremetabolitt. Metoden må valideres og prøves ut på reelle blodprøver fra pasienter behandlet med klopidogrel. |
| URI: | http://hdl.handle.net/10037/2212 |
| Abstract: | Chitosan is currently proposed to be one of the most promising polymers in wound dressing development. Our research focuses on its potential as a vehicle for nano-delivery systems destined for burn therapy. One of the most important features of wound dressing is its bioadhesion to the wounded site. We compared the bioadhesive properties of chitosan with those of Carbopol, a synthetic origin polymer. Chitosan-based hydrogels of different molecular weights were first analyzed by texture analysis for gel cohesiveness, adhesiveness and hardness. In vitro release studies showed no difference in release of model antimicrobial drug from the different hydrogel formulations. Bioadhesion tests were performed on pig ear skin and the detachment force, necessary to remove the die from the skin, and the amount of remaining formulation on the skin were determined. Although no significant difference regarding detachment force could be seen between Carbopol-based and chitosan-based formulations, almost double the amount of chitosan formulation remained on the skin as compared to Carbopol formulations. The findings confirmed the great potential of chitosan-based delivery systems in advanced wound therapy. Moreover, results suggest that formulation retention on the ex vivo skin samples could provide deeper insight on formulation bioadhesiveness than the determination of detachment force |
| URI: | http://hdl.handle.net/10037/4921 |
| Abstract: | Background: Pharmaceutical care is delivered in various ways and settings. There is a need for ways of describing the care delivered to be able to compare the care delivered in different settings. Aim and objectives: The aim of the project was to compare the prescribing activity and delivery of pharmaceutical care in two clinical settings. In order to quantitatively compare the pharmaceutical care activity, a categorisation system for pharmaceutical care issues previous developed at University of Strathclyde was used. This categorisation system was modified as part of this and three other projects before it was used. Methods: The categorisation system was modified through literature review and discussions between the four researchers. Categorisation of care issues was used to quantitatively describe the delivery of pharmaceutical care at a Care of the Elderly ward. The data was also used to statistically compare the delivery of pharmaceutical care with another ward at the same hospital. Two separate projects surveyed the prescribing activity at the two wards, and the results from these are included in this project. Results: The comparison of pharmaceutical care between the two wards showed that the pharmacists had different focus in the delivery of care. Differences in prescribing activity were also showed between the two wards. Discussion: The difference in pharmaceutical care activity can be explained by differences in patient population, prescribing activity and pharmacist preferences. The data collection was based upon documentation made by the pharmacists during their work in the clinical setting. Variations in recording can have contributed to the differences seen. Conclusion: The categorisation system can be used to describe and compare delivery of pharmaceutical care in different settings. |
| URI: | http://hdl.handle.net/10037/1581 |
| Abstract: | Curcumin (I), demethoxy curcumin (II) and bisdemethoxy curcumin (III) are commonly called curcuminoids, and derived products from the spice, turmeric. It has reported numerous of therapeutic activities including, anti-inflammatory, and anticancer properties. The aim of the current study was to develop a formulation which can overcome the limitation of curcumin being so poorly soluble in aqueous medium. Our approach has been directed toward investigating the potential of using liposomal formulations as carrier system for curcumin destined for treatment of vaginal inflammation. Curcumin containing liposomes were prepared using soya phosphatidylcholine by the modified film method. Moreover, we added cholesterol in various molar ratios to affect the vesicle membrane rigidity. Curcumin entrapped in the liposomes was quantified and the entrapment efficiency was found to be reaching up to 100%. The size and size distribution of liposomes were determined on photon correlation spectroscopy. The results showed an increase in size of liposomes containing curcumin in comparison with empty liposomes. The accelerated stability testing was used to predict the stability of the formulations. The test revealed changes in the characteristics of the liposomes. The free radical scavenging activity (DPPH) assay of curcumin and Curcuma extract, as well as isolated pure curcumin I, revealed that curcuminoids mixtures have stronger activity. |
| URI: | http://hdl.handle.net/10037/2751 |
| Abstract: | Abstract Background There is a need for a common way of documenting and planning pharmaceutical care within the electronic prescribing system used at Ayr hospital. Aims and objectives Conduct a contents analysis of care issues in a formal survey of the care plans in order to categorise the issues, and propose a starting point for an electronic care plan template. Methods Documentation of pharmaceutical care and the distribution of care issues in two different settings were investigated in a prospective, clinical audit. A categorisation system was modified and guideline for this categorisation system was made, and documented care issues were subsequently subject to content analysis in the system. All results were evaluated in a focus group. A proposal for an electronic care plan template was made Results It was confirmed in a focus group meeting that the electronic care plan template had captured the needs set by the pharmacists at Ayr Hospital. The validity and usability of the different parts of the categorisation system differed. The content analysis of care issues between two wards at Ayr Hospital showed differences in the mean value of care issues per patient and also the type of care issues most commonly seen at the wards. Conclusion An electronic care plan template have great potentials. The categorisation system as a whole needs further development, since certain parts of it were ambiguous. |
| URI: | http://hdl.handle.net/10037/1582 |
| Abstract: | Det har lenge vært hevdet at DNA som finnes i mat er innskrenket til, og blir hurtig degradert i fordøyelsessystemet til pattedyrene. Denne antagelsen har vist seg å være riktig for majoriteten av DNA i mat som går inn i fordøyelsessystemet, men mange studier har vist at denne degraderingen ikke skjer 100 %. DNA er et stabilt molekyl som kan overleve forholdene i fordøyelsessystemet, og herfra muligens bli tatt opp inn i celler, blodomløp og andre organer. Dette har i studier vist seg å kunne skje. Hvis fremmed DNA blir tatt opp av celler er det også en mulighet for at det kan bli integrert inn i vertenes eget kromosom. Integrasjon av fremmed DNA i mammalske celler er sannsynlig en meget lav frekvensbegivenhet som in vivo er nesten umulig å detektere med nåværende tilgjengelig metodikk. Dette studiet bruker en tarm enterocyte lignende cellelinje (Caco-2) til å undersøke muligheten av spontant opptak og mulig integrasjon av fremmed DNA in vitro. DNAet som ble brukt som markør er plasmidet pRc/CMV-SLT. Det inneholder Simian Virus 40 sitt stort T-antigen som har vist seg å ha onkogenisk potensiale under kontroll av den menneskelige cytomegalovirus promoter. Hvis integrert inn i de mammalske cellene, ville utvendig forandringer være synlige ved at det forandrer cellens morfologi. PCR som amplifiserer stort T-antigen sekvensen ble brukt til å analysere DNAet som ble isolert fra celle kulturene. Cellene som ble dyrket i tilstedeværele av plasmidet pRc/CMV-SLT ga positive signaler for stort T-antigen når amplifisert med PCR. Men denne metoden kunne ikke angi om DNAet som ble detektert faktisk hadde blitt tatt opp av cellene og var integrert. Ingen visuelle forandringer av morfologien til cellen ble observert i løpet av studiet. |
| URI: | http://hdl.handle.net/10037/2175 |
| Abstract: | A study of mortality for all patients with schizophrenia admitted to the University Hospital of North Norway during 1980-2006 was performed, with a special focus on gender differences and changes in mortality during a period of transition from hospital-based to community-based care. A total of 1111 patients with schizophrenia were included, and the cohort was linked to the Causes of Death Register of Norway. Males and females had 3.5 and 2.6 times, respectively, higher mortality than the general population. The standardized mortality ratios were higher during the last nine years than the first nine years, and for women admitted after 1992, we found evidence for an increasing difference in mortality compared to the general female population as well as an increase in absolute mortality. In the subgroup of patients who had always been admitted voluntarily, women tended to have higher mortality, and a particularly high standardized mortality rate (SMR) was found in this group of female schizophrenic patients. Our results confirmed a persisting mortality gap between patients with schizophrenia and the general population over a period of 27 years, with a tendency of increasing standardized mortality ratios over time. The SMR for total mortality of women with schizophrenia is rising and becoming just as high as for men, both for unnatural and natural causes of death. |
| URI: | http://hdl.handle.net/10037/4096 |
| Abstract: | Samandrag Masteroppgåva er ein del av prosjektet ”Bruk av Marevan (warfarin) i klinisk praksis”. Tidlegare er det gjennomført pilotstudie og spørjeundersøking blant pasientar som henta Marevan® frå apotek i Tromsø. Det er under utvikling eit verktøy (Anticoagulation Tool warfarin, ATw) der det blir vurdert om behandlinga av kvar einskild pasient oppfyller visse kriterier. Verktøyet skal kunne brukast til evaluering av warfarinbehandling og skal prøvast ut på profilar for pasientar som tok del i spørjeundersøkinga. Formål Det overordna formålet med studien ”Bruk av Marevan (warfarin) i klinisk praksis” var å kartleggje klinisk praksis for oppstart og gjennomføring av warfarinbehandling i Tromsø, gjere synleg kvar det eventuelt skjer svikt og fremje forslag til betre gjennomføring av behandlinga. Hensikta med masteroppgåva var å byggje opp ein database med relevante journaldata, og bruke denne som grunnlag for utprøving av eit verktøy (ATw) for evaluering av warfarinbehandling under norske forhold. Material og metode Studiepopulasjonen i masteroppgåva var 65 apotekkundar i Tromsø som brukte Marevan® på det tidspunktet dei vart spurt om å ta del i studien. Pasientane som tok del i journalstudien har i ei tidlegare undersøking svara på spørjeskjema om bruk av Marevan. Ein database for journaldata vart opparbeidd av masterstudenten. Informasjon samla frå spørjeundersøking og journalar vart overført til eit verktøy (ATw) for evaluering av antikoagulasjons¬behandling. Verktøyet vart evaluert i forhold til kor enkelt det var å forstå og bruke, og om nødvendig informasjon kunne finnast i det tilgjengelege datamaterialet som første ledd i valideringa av verktøyet. Det vart kalkulert score for dei ulike svaralternativa og appliseringsgrad og svarprosent for kvart enkelt kriterium. Som mål på behandlingskvalitet i pasientgruppa vart det brukt prosentdel oppfylte kriterier for god behandling i forhold til appliserbare kriterier. For å kunne identifisere ”care issues” vart tal på ikkje oppfylte kriterier brukt. Resultat Databasen inneheldt ved registreringsstans journaldata for 65 pasientar. Fire kriterier vart endra før verktøyet vart tatt i bruk. Det vart fremja forslag for fleire endringar i verktøy, rettleiing og journaldatabase. Tre kriterier var det vanskeleg å finne tilstrekkelege data for i journal. Det foreløpige datamaterialet viste at prosentdel oppfylte kriterier var på 62,5 % for journaldelen og for spørjeundersøkingsdelen 45,4 %. I gjennom¬snitt var 26,8 % av appliserbare kriterier svara med Nei for journaldelen og 44,9 % for spørjeundersøkingsdelen. Få pasientar hadde meir enn 12 veker mellom INR-målingane. Det var sjeldan notert i journal at informasjon var gitt til pasienten. Mange epikriser mangla viktige opplysingar om oppstart av behandling. INR-mål vart ofte funne i AK-journal. Ved INR > 4,5 vart det i dei fleste tilfella målt ny INR etter 1-2 veker. For 10 av 17 episodar med INR > 4,5 var det ikkje notert at warfarin var midlertidig seponert. Konklusjon Verktøyet ATw kan brukast til å kartleggje warfarinbruk ut frå spørjeundersøking og informasjon frå journalar i ein database, men utvida validering må utførast før det er pålitelig nok til evaulering av warfarinbehandling. I gjennomsnitt var 54 % av anvendte kriterier oppfylt (svara med Ja). Databasen fungerer tilstrekkeleg for datamateriale av moderat storleik. Det kan bli enklare å bruke verktøyet med ein betre tilpassa journal¬database. |
| URI: | http://hdl.handle.net/10037/1176 |
| Abstract: | Industrial chemicals, pesticides and other similar compounds are all known to be a burden for the environment. In high concentrations they can all affect the biological environment in a manner that is dangerous for organisms. The presence of pharmaceuticals and personal care products (PPCPs) in the environment are of great interest regarding to their potential toxicity. Pharmaceuticals and PPCPs are discovered in soil, sludge, sewage and in the adjacent aquatic environment. The aim of this study was to develop and optimize a hollow fiber liquid- phase microextraction (HF-LPME) method for extraction and pre-concentration of benzodiazepines and its metabolites in sewage water. Different parameters like donor- and acceptor phases, fibers and organic phases were to be tested. The compounds that was to be investigated in this study were chosen by looking at sales statistics for benzodiazepines in Norway over a three years period, 2005-2007. Some metabolites of the compounds were also included. The chosen compounds were zopiclone, zopiclone-d8, zopiclone N-oxide, N-desmethyl zopiclone hydrochloride, zolpidem, zolpidem-d6, alprazolam, alprazolam 5-oxide, 1-hydroxy alprazolam, midazolam, midazolam- d5 and 1`-hydroxy midazolam. Later in the project clonazepam and 7-aminoclonazepam were included. Sewage water samples were collected at Langnes Sewage Treatment Plant (STP), Tromsø, before they were filtered and extracted by hollow fiber liquid phase microextraction and analysed on Ultra Performance Liquid Chromatography- Mass Spectrometry/ Mass Spectrometry (UPLC- MS/MS). Quantifiable amounds of zolpidem was found during the collection in January, midazolam and 1- hydroxyl midazolam were detectable. In April 1- hydroxy midazolam, midazolam and zolpidem were detectable. |
| URI: | http://hdl.handle.net/10037/2211 |
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