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Rakvaag, Hilde (Master thesis; Mastergradsoppgave, 19-Jun-2007)[+][-]
Abstract: Makrofager kan utgjøre en betydelig del av en kreftsvulst. Det er tidligere vist at monocytter ved differensiering mot makrofager uttrykker økte mengder av enkelte cysteinproteaser. Maligne celler er vist å bruke cysteinproteaser i forbindelse med metastasering, og endogene cysteinproteasehemmere antas å kunne hemme denne prosessen. Det var derfor interessant å studere reguleringen i uttrykk og aktivitet av cystatiner ved differensiering av monocyttiske celler mot makrofager. Det ble etablert en funksjonell metode for måling av inhibitorisk aktivitet mot cysteinproteaser i laboratoriet ved hjelp av fluorometrisk måling med cysteinproteasen papain som enzym. Metoden ble brukt til å måle inhibitorisk aktivitet av cystatiner i THP-1 celler (en human monocyttliknende akutt leukemisk cellelinje), i diverse humane kreftcellelinjer, i diverse xenografter (human/mus), og i cystatin M-transfekterte HEK 293 celler (nyreepitelceller). THP-1 celler ble stimulert med PMA (40 ng/ml) i 24 timer, og dyrket i opptil 10 dager. Ved stimulering med PMA gikk cellene fra å være frittlevende monocytter til å bli adherente makrofager. Grad av inhibitorisk aktivitet ble regnet ut i inhibitoriske enheter per mg totalprotein for cellelysater og inhibitoriske enheter per ml for cellemedier. En inhibitorisk enhet ble definert som den konsentrasjonen som må til for å hemme 50 % av papainaktiviteten. Uttrykk av cystatinene C, M og F ble analysert ved hjelp av immunodeteksjon (Western blotting). Det ble sett på endring av total inhibitorisk aktivitet over tid, og en eventuell sammenheng mellom inhibitorisk aktivitet og uttrykk av cystatin C, F og M. Målingene i medieprøver fra cystatin M-transfekterte celler viste tydelig økt inhibitorisk aktivitet i de transfekterte cellene, noe som bekreftet at metoden fungerte for å måle hemming forårsaket av ekstracellulært cystatin M. Det ble observert en tidsavhengig økning i inhibitorisk aktivitet både i cellelysater og cellemedier. Uttrykk av cystatin C og M ble detektert, men ikke cystatin F. Det ble observert en sammenheng mellom den tidsavhengige økningen i ekstracellulær inhibitorisk aktivitet og uttrykk av ekstracellulært cystatin M. URI: http://hdl.handle.net/10037/1187 File(s) in this item: 1
thesis.pdf (443.1Kb) -
Rasmussen, Viktoria Emily (Master thesis; Mastergradsoppgave, 28-Aug-2009)[+][-]
Abstract: Natural transformation is one of three ways for bacteria to acquire genetic material (DNA) horizontally. Several hypotheses exist for why some bacteria have this ability to take up DNA, and what the incoming DNA is used for. These include use of DNA for recombination, repair or as nutrients. This master study focuses on the “food hypothesis”. This hypothesis implies that the exogenous DNA is either used in the synthesis of new DNA and RNA molecules, or broken down to carbon, nitrogen and phosphate to use as energy and in synthesis of new nucleotides. The naturally transformable Acinetobacter baylyi is used as a model organism to test this hypothesis. By removing the comFECB operon from the wild type bacteria a non-transformable strain is produced. Comparisons of growth rates between these two strains in monocultures give the absolute fitness, whereas co-cultures give the relative fitness. If the comFECB operon has evolved as a means to use DNA as food, than the transformable wild type would have a fitness advantage over the non-transformable strain when DNA is the only nutrient in the growth media. Although the addition of DNA to the growth media resulted in increased growth of A. baylyi, this effect was seen in both strains, independently of functional com-genes. This implies that DNA is in fact used as nutrients by this species, but not only by natural transformable bacteria with intact comFECB operons. The experiments done in this thesis do therefore not offer support for the “food hypothesis”. URI: http://hdl.handle.net/10037/2208 File(s) in this item: 1
thesis.pdf (268.0Kb) -
Reiersen, Anne-Lise (Mastergradsoppgave; Master thesis, 08-Jun-2006)[+][-]
Abstract: Innledning. Den revmatiske pasienten får ofte livslang legemiddelbehandling for sin kroniske sykdom. Behovet for legemiddelinformasjon er stort. Hensikt. Hensikten med studien var å undersøke pasientenes erfaringer med legemiddelinformasjon ved revmatologiske avdelinger på utvalgte sykehus i Norge. Studien søkte å finne ut hvem som ga informasjon, hvor tilfredse pasientene var med den, hvordan den best kunne organiseres, og om det gjorde noen forskjell om det var farmasøyt eller annet helsepersonell som ga informasjon. Metoder. En kombinasjon av kvalitative intervju med helsepersonell og en kvantitativ spørreskjemaundersøkelse for utskrevne pasienter, fra revmatologiske avdelinger ved Universitetssykehuset Nord-Norge, Nordlandssykehuset, St. Olavs Hospital og Diakonhjemmet Sykehus, ble utført. Intervjuene ga bakgrunnsopplysninger for analysering av svarene i spørreskjemaundersøkelsen. Resultater. Studien hadde en svarprosent på 51% og antallet respondenter var 250. Legene ga informasjon i størst grad, etterfulgt av sykepleierne og så i minst grad farmasøytene. Et mindretall (37%) av respondentene fikk legemiddelinformasjon fra team med farmasøyt. 58% av respondentene som begynte med nye legemidler, fikk både muntlig og skriftlig informasjon, mens det var 81% av dem som foretrakk det. Respondentene var mest tilfredse med informasjon fra team med farmasøyt (p < 0,001), og med informasjon som var både muntlig og skriftlig (p < 0,001). Konklusjoner. Revmatiske pasienter er mest tilfredse med legemiddelinformasjon når de får den fra team med farmasøyt, og når den er både muntlig og skriftlig. Det er potensial for å gjøre legemiddelinformasjonen bedre for pasientene ved revmatologiske avdelinger på sykehus i Norge, og farmasøyter kan bidra til det. URI: http://hdl.handle.net/10037/25 File(s) in this item: 1
thesis.pdf (1.347Mb) -
Risberg, Kine (Master thesis; Mastergradsoppgave, 20-May-2010)[+][-]
Abstract: Escherichia coli(E.coli) belongs to the Enterobacteriaceae family of gram negative rods. It is the most common cause for bacterial sepsis. According to NORM (Norwegian system for surveillance of antibiotic resistance in microbes); E.coli is the main pathogen found in blood samples from humans submitted to Norwegian microbial laboratories (page 49 NORM report 2008)(1). E.coli is also the most common cause of human urinary tract infections (The Journal of the Norwegian Medical Association) (2). Empiric treatment for sepsis and urosepsis in Norway is betalactam antibiotics in combination with aminoglycosides(3). In case of allergy, patients with urosepsis are treated with quinolones and aminoglycosides(4). There is concern related to recent years development of resistance against gentamicin (aminoglycoside) and ciprofloxacin (quinolone) among E.coli strains (page 52 NORM report 2008) (1). This work was initiated as a first step to identify the most common mechanisms for aminoglycoside resistance in Enterobacteriaceae collected in western Norway. The focus for this work was to characterize antibiotic resistance and detect the presence of the genes encoding two aminoglycoside modifying enzymes. The genes chosen encodes two enzymes from the group aminoglycoside acetyltransferases (AAC`s); aac(6`)-Ib and aac(3)-IIc (aacC2). The use of ciprofloxacin has increased markedly during the past few years. Recent studies have reported a variant of AAC(6`)-Ib characterized by two amino acid changes, Trp102Arg and Asp179Tyr. This variant called AAC(6`)-Ib-cr inflicts ciprofloxacin resistance in addition to aminoglycoside resistance. We suspected that increased use of ciprofloxacin could cause selection of isolates resistant to aminoglycosides by selecting the isolates that possess AAC(6`)-Ib-cr. We decided to examine the prevalence of aac(6`)-Ib-cr in isolates of Enterobaceriaceae resistant aminoglycosides, in order to provide either indirect support or rejection of this hypothesis. URI: http://hdl.handle.net/10037/2747 File(s) in this item: 1
thesis.pdf (1.522Mb) -
Rist, Maria (Master thesis; Mastergradsoppgave, 07-Jun-2011)[+][-]
Abstract: The incidence rate of malignant melanoma is increasing in Norwegian population as well as worldwide. It’s one of the most aggressive human cancers showing exceptional abilities to metastasize and develop resistance to therapy, and ccurrently there are no effective treatments against metastatic melanoma. Traditionally, melanoma aggressiveness was linked to intrinsic properties of the malignant cells themselves. However, it is becoming apparent now that the tumour microenvironment (TME) factors – non-malignant (stroma) cells, soluble molecules and extracellular matrix components – can play an important role in modulating metastatic properties and drug-sensitivity of cancer cells. In the present work we investigated how various TME factors like extracellular matrix components like fibronectin and laminin and soluble factors released from mice organs – common sites of melanoma metastasis - affected melanoma cells, specifically their metastasis-associated properties like growth/proliferation and sensitivity to the experimental dug Elesclomol. The study was based on three-dimensional (3D) in vitro cultures, where melanoma cells were grown in a Collagen or Matrigel matrix in the presence of investigated factors of TME. Two melanoma cells lines, Melmet 1 and Melmet 5 derived from the metastatic melanoma patents with different clinical indications were employed. It was observed that fibronectin and laminin did not have a notable effect on cell growth or viability. However, the soluble factors from the organs showed a slight stimulating effect on cell growth and a notable effect on cell morphology and growth pattern. The latter was especially pronounced for the bone marrow-derived factors. Comparison of the sensitivity of Melmet cells to Elesclomol in 3D versus 2D revealed, that 3D cultures were less sensitive to the drug, and that Melmet 5 was less sensitive compared to Melmet 1. The sensitivity was not modulated by the soluble factors derived from the healthy or metastatic brain. URI: http://hdl.handle.net/10037/3405 File(s) in this item: 1
thesis.pdf (1.412Mb) -
Rud, Ane Kristine Kongsgaard; Lund-Iversen, Marius; Berge, Gisle; Brustugun, Odd Terje; Solberg, Steinar; Mælandsmo, Gunhild; Pedersen, Kjetil Boye (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)[+][-]
Abstract: The metastasis-promoting protein S100A4 induces expression of ephrin-A1 and osteopontin in osteosarcoma cell lines. The aim of this study was to investigate S100A4-mediated stimulation of ephrin-A1 and osteopontin in non-small cell lung cancer (NSCLC) cell lines, and to characterize the expression of these biomarkers in primary tumor tissue from NSCLC patients. Four NSCLC cell lines were treated with extracellular S100A4, and ephrin-A1 and osteopontin expression was analyzed by real time RT-PCR and Western blotting. Immunohistochemical staining for S100A4, ephrin-A1 and osteopontin was performed on tissue microarrays containing primary tumor samples from a cohort of 217 prospectively recruited NSCLC patients, and associations with clinicopathological parameters were investigated. S100A4 induced ephrin-A1 mRNA and protein expression in adenocarcinoma, but not in squamous carcinoma cell lines, whereas the level of osteopontin was unaffected by S100A4 treatment. In primary tumors, moderate or strong immunoreactivity was observed in 57% of cases for cytoplasmic S100A4, 46% for nuclear S100A4, 86% for ephrin-A1 and 77% for osteopontin. Interestingly, S100A4 expression was associated with ephrin-A1 also in vivo, but there was no association between S100A4 and osteopontin. Expression levels of S100A4 and ephrin-A1 were significantly higher in adenocarcinomas compared to other histological subtypes, and S100A4-positive tumors were smaller and more differentiated than tumors without expression. Our findings suggest that S100A4, ephrin-A1 and osteopontin are involved in the biology of NSCLC, and further investigation of their potential use as biomarkers in NSCLC is warranted. URI: http://hdl.handle.net/10037/4903 File(s) in this item: 1
article.pdf (721.6Kb) -
Ruud, Maren Rambøl (Master thesis; Mastergradsoppgave, May-2008)[+][-]
Abstract: Objective This audit was conducted by reviewing two cohorts of patients in terms of pharmaceutical care delivered by examining free text electronic records and categorising care issues into a proposed reporting system. Qualitative research methods in an action research process were used to test the validity and the utility of the reporting system. A template for an electronic pharmaceutical care plan that meets defined criteria for service developments including non-medical prescribing was proposed by the investigators. Methods The investigator identified and gathered documented care plans from samples of patients receiving pharmaceutical care during February 2008 to April 2008 using the electronic care monitoring system. The context and outcomes of each care plan were identified by obtaining additional information from paper case records and through dialogue with the clinical pharmacist authors to overcome any gaps in the free text electronic records. An existing categorisation system used at the University of Strathclyde was modified to increase the robustness and clinical usefulness and a guideline for use of the system was developed. A contents analysis of the care plans was conducted in order to categorise the care issues. The inter-rater reliability in the categorisation of the care issues in the survey was demonstrated using Cohens kappa analysis. The proposed care plan template was evaluated in terms of validity and utility for reporting care plans using an action research approach and revised in response to the feedback obtained. The survey findings were also reported to the clinical pharmacy team. Setting The survey was sited at the orthopaedic ward at the Ayr Hospital where an electronic prescribing system is in use. A clinical pharmacist is at the orthopaedic ward every day from Monday to Friday. Results Ideas generated from group meeting with the clinical pharmacist at the Ayr Hospital were among others to implement databases and forms that already are used today. The care issue section should be more structured and include functions as review date and predefined texts. The 90 patients that were included at orthopaedic ward had totally 270 care issues identified compared to the 71 patients at the cardiology ward where totally 377 care issues were identified (p<0.0001). The number of care issues per patient categorised as a Check was significant higher at the cardiology ward than the orthopaedic ward (3.8 versus 1.1, p<0.0001). The subcategory ‘Change in clinical (shared) record of drug history’, which includes changes in the patients drug therapy based on errors or omissions in medicines prescribed on admission, was relative high on both wards (63 issues on orthopaedic and 37 on cardiology). For both wards most of the Checks were done during the treatment of the patient and therefore categorised as a ‘monitoring’. Similarly were the majority of care issues in both of the Change categories found at the ‘verification’ stage in the delivery of the patient’s treatment. Few ‘reviews’ were identified among the ‘Changes in drug therapy’ in both settings. The inter-rater reliability test for the categorisation found the agreement to be highest within the Check and the two Change categories and poorest in the part of the system with the Quality Assurance Descriptors ‘Degree of change’. Conclusion A care plan template will make the plan more structured and complete and the documentation process more effective and uniform between pharmacists. The categorisation system describes the contribution the clinical pharmacist to the patient’s treatment but there is a need for a language within the pharmaceutical care. URI: http://hdl.handle.net/10037/1589 File(s) in this item: 1
thesis.pdf (1.084Mb) -
Salbu, Linda; Picker-Freyer, Katharina M.; Schmid, Wolfgang; Bauer-Brandl, Annette; Tho, Ingunn (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)[+][-]
Abstract: This study examines the contribution of the 3-D model in an early development set-up for pectin tablets. Therefore, the aim of this work is to extract as much information on the compression behaviour from as few tablets as possible. Pectins with various degrees of methoxylation (DM) were studied (4-72%). The compressibility was evaluated by classical “in-die” Heckel and Kawakita analyses in addition to the 3-D modelling. For validation purposes well-known reference materials were included. 3-D modelling applied on data of single tablets yielded a certain degree of information on the compressibility. When several tablets with different maximum relative densities were included, no additional information was gained in the classical evaluation, whereas the 3D-model provided additional information through the shape of the 3-D parameter plot: pectins with a DM ? 25% consolidated predominantly by elastic deformation similarly to the 3-D parameter plot of pregelatinized starch (PGS). The 3-D analysis also suggests some degree of fragmentation, and for some of the low-methoxylated pectins (DM ? 10%) viscoelastic deformation. This study showed that by application of 3-D modelling it is possible to differentiate elastic and viscoelastic materials, if tablets of different maximum relative densities are evaluated. URI: http://hdl.handle.net/10037/4486 File(s) in this item: 1
article.pdf (494.2Kb) -
Seippel, Ninja Elise A (Master thesis; Mastergradsoppgave, 20-May-2009)[+][-]
Abstract: For at en kreftsvulst skal kunne spre seg må kreftcellene ha evnen til å bryte ned den ekstracellulære matriksen (ECM) som holder dem på plass. De må også kunne bevege seg ut fra svulsten og over i lymfesystemet eller blod for å transporteres til et nytt organ. Plasminogen aktivator systemet er en samling av proteiner som aktiverer hverandre og hvor disse aktiveringene fører til nedbrytning av ECM. Det systemet er derfor med på å bidra til at kreftsvulster kan spre seg til nye vev. Urokinase plasminogen aktivator reseptoren (uPAR) er en del av dette system og er vist å være overuttrykt på overflaten til flere typer kreftceller. Det er derfor trolig at det er en sammenheng mellom overuttrykk av uPAR i kreftceller og deres evne til å spre seg. Det er også vist at uPAR kan interagere med transmembranreseptorer i integrinfamilien og at denne interaksjonen også øker evnen cellen har til å bevege seg gjennom ECM. I denne oppgaven skulle man teste ut uPAR sin påvirkning på kreftcellers evne til å bevege seg og til å bryte ned ECM. cDNAet til uPAR ble klonet og sekvensene til dette cDNAet ble bekreftet av restriksjonskutting og DNA-sekvensering. Deretter ble cDNA som kodet for uPAR forsøkt stabilt uttrykt i to forskjellige humane kreftcellelinjer slik at man kunne tesete de migratoriske og invasive egenskapene deres. Det ble også gjort migrasjons- og invasjonsanalyser på celler fra mus som hadde uttrykk av humant uPAR og hvor den ene subenheten (β1) av integrinene var slått ut. Ved denne testingen ville man også kunne si noe om interaksjonen mellom uPAR og integriner. Nivået av uPAR i alle cellelinjene ble bestemt ved hjelp av Western blot. Av ulike årsaker lykkes det ikke å få dannet stabile kloner av uPAR i verken UT-SCC-12A eller U2OSTA. De migratoriske og invasive egenskapene til musecellene GD25, GD25- uPAR, GD25β1 og GD25β1- uPAR ble testet ved hjelp av Wound Healing assay og invasjonsassay. Ut fra disse testene var det vanskelig å trekke en bestemt konklusjon om uPAR hadde påvirkning på de migratoriske og invasive egenskapene til disse cellene. URI: http://hdl.handle.net/10037/2199 File(s) in this item: 1
thesis.pdf (3.247Mb) -
Skare, Erik Eidem (Master thesis; Mastergradsoppgave, Jun-2009)[+][-]
Abstract: Bakgrunn: Masteroppgaven er en del av et doktorgradsprosjekt for utvikling av en klinisk farmasøytisk service for pasienter med etablert CHD. Legemiddelrelaterte problemer kan gi økte kostnader og redusert klinisk effekt av medisinsk behandling, og gode verktøy for vurdering av kvalitet i legemiddelbehandling er mangelvare. Forekomsten av CHD er økende i den vestlige verden, og en økende andel av hjerte-karpasienter behandles sekundærprofylaktisk livet ut som følge av CHD. Et verktøy for å vurdere kvaliteten i sekundærprofylaktisk legemiddelbehandling ved CHD er i denne studien validert og anvendt på en pasientpopulasjon. Verktøyet; et Medication Assesement Tool vurderer hvorvidt behandlingen som er gitt samsvarer med kliniske retningslinjer. Materiale og metode: Et tidligere utviklet MAT (MAT- CHDsp) for sekundærprofylakse ved CHD ble validert, revidert og anvendt på pasientpopulasjon med etablert CHD. Validering ble gjort før og etter revidering av MAT- CHDsp og bestod av testing av reproduserbarhet ved intra og inter – rater test, gjennomførbarhet ved tidsbruk og appliserbarhet og klinisk samsvar ved adherence. Revidert MAT- CHDsp ble retrospektivt anvendt på et materiale bestående av 298 pasienter som fikk implantert stent ved hjertemedisinsk avdeling, UNN i 2008. Resultater: Overordnet reproduserbarhet for mat MAT -CHDsp var utmerket før og etter revidering, men enkelte kriterier hadde lav reproduserbarhet. Erfaring og trening med applisering av MAT- CHDsp viste seg å gi lavere tidsbruk. Det var ingen signifikant endring av kappa før og etter revidering av MAT -CHDsp. Prevalens for CHD dominerte i aldersgruppen 60 -80år der 79,2 % av populasjonen var menn. Adherence til anbefalt behandling var overordnet moderat, der enkelte kriterium hadde problematisk adherence. Etablering av platehemmende, lipidmodifiserende og blodtrykksenkende behandling var tilfredsstillende, men der de to siste grupper hadde begrenset samsvar for oppnåelse av behandlingsmål. Fortolkning: Et MAT rettet mot sekundærprofylakse ved koronarsykdom er validert og anvendt for kvalitetssikring av legemiddelbehandling for pasientgruppen. Paradoksale resultater ved bruk av Cohen`s kappa kan ha bidratt til usikker reproduserbarhet hos enkelte kriterium og det anbefales inklusjon av separate mål for enighet ved fremtidig bruk av kappa som mål for reproduserbarhet. Fordeling av MI og AP for pasienter med koronarsykdom viser liten kjønnsmessig forskjell der tileggsdiagnoser som hypertensjon, DM og KOLS inkluderer sykdomsbildet hos flere av pasientene. Samsvar til sekundærprofylaktisk legemiddelbehandling synes tilfredsstillende, men der oppnåelse av behandlingsmål er begrenset. URI: http://hdl.handle.net/10037/2745 File(s) in this item: 1
thesis.pdf (1.257Mb) -
Skarsaune, Mona (Master thesis; Mastergradsoppgave, Jun-2008)[+][-]
Abstract: Abstract Background Pharmaceutical care planning is increasingly seen as the most effective manner by which to deliver pharmaceutical care services to the patient. The role of the pharmacist, both specialist and generalist, is paramount, as much of the treatment in Mental Health is dependent on the effective management of the patients medication(1). Consequently, there is a need for standardised pharmaceutical care planning within the speciality. In Scotland, the Mental Health Pharmacy Strategy Group (MHPSG) commissioned a project to develop and implement a care plan document that could be used at a national level. This project has taken on the recommendations from that study to re-design and validate a standardised document for pharmaceutical care planning in a psychiatric in-patient population. Methods Recommendations from the MHPSG’s study and candidate care issues specific to mental health pharmacy were identified and incorporated into the re-design of the care plan document. A small field test was then conducted in NHS Lothian, where 12 care plans were completed by six pharmacists. Feedback from this study was used to re-develop a 2nd draft, which was subjected to peer review and assessment by focus group discussion. The focus group consisted of clinical mental health pharmacists from different health board areas who discussed the content, layout and general utility of the document. Findings from this discussion informed the re-development of a final version of the care plan document. Results A four page standardised document that will enable a uniform care planning approach within mental health pharmacy. Conclusion The development of a national care planning system is a labour intensive process. This project has managed to produce a care plan that may be used as a standard within mental health in-patients after further validation. Whilst the majority of pharmacists are aware of its benefits, several issues became apparent which may impede its implementation and use. URI: http://hdl.handle.net/10037/1595 File(s) in this item: 1
thesis.pdf (1.687Mb) -
Skogdalen, Kjersti (Master thesis; Mastergradsoppgave, Jun-2010)[+][-]
Abstract: Beboere på sykehjem ofte flere og kompliserte medisinske problemer. Dette skyldes at de bruker i gjennomsnitt fem legemidler fast daglig og at alder, organfunksjon, mentalsvikt og ernæringstilstand kan gjøre dem mer følsomme for bivirkninger og interaksjoner. Legemiddelbehandlingen blir derfor kompleks og medfører stor risiko for legemiddelrelaterte problemer. Legemiddelgjennomganger kan være et kvalitetssikrende tiltak for å håndtere legemiddelrelaterte problemer. Formålet med denne oppgaven var å finne en god arbeidsmetode for legemiddelgjennomganger på sykehjem, vurdere screening som metode og NORGEP-kriteriene som inklusjonskriterier. Fire sykehjem ble inkludert i kartleggingen av NORGEP-kriteriene og seks sykehjemsleger ble invitert til å delta i legemiddelgjennomganger. Totalt ble 164 pasienter inkludert i NORGEP-kartleggingen. Syv pasienter fikk sin legemiddelbehandling vurdert i en legemiddelgjennomgang. Blant de 164 inkluderte pasientene, hadde 54 % av pasientene treff på minst ett kriterium. Fem pasienter hadde treff på fire kriterier. Blant de syv pasientene som fikk en legemiddelgjennomgang, hadde seks pasienter treff på NORGEP-kriteriene. Alle disse seks hadde treff på kriterium 36 som førte til endringer i legemiddelbehandlingen. Blant de syv pasientene ble 14 legemidler gitt fast og 18 behovsmedisiner seponert. Det ble utarbeidet en metode for legemiddelgjennomganger, men det må gjøres flere legemiddelgjennomganger, da denne studien inkluderer for få pasienter til å konkludere. NORGEP-kriteriene ble vurdert mer klinisk relevant enn de fleste interaksjonene funnet i interaksjonsdatabaser, som kan tyde på at de er gode inklusjonskriterier. URI: http://hdl.handle.net/10037/2744 File(s) in this item: 1
thesis.pdf (12.54Mb) -
Skogly, Stian (Master thesis; Mastergradsoppgave, 20-May-2009)[+][-]
Abstract: Introduction — The aim of Edinburgh Improved Anticipatory Care and Treatment (IMPACT) service is to reduce admissions and re-admissions to hospital for people with LTCs. The service consists of nurse case managers co-ordinating patients’ care, including reviewing medication. As a pilot project, an arrangement was made to refer such patients to a team of primary care pharmacists for clinical medication review. This project will examine the pharmaceutical care needs of this particular patient group and prepare an electronic system for reporting pharmaceutical care contributions in the evaluation of this service. Methods — A model of care for COPD was generated to characterise the pharmaceutical care needs of patients recruited into the anticipatory care service from a pharmacy perspective. A generic database was designed for the purposes of characterising patients and for addressing their pharmaceutical care needs. Anonymous and categorised pharmaceutical care plans from the pharmacists conducting the medical reviews was used to populate the database. A pharmaceutical care plan for COPD was proposed to match the database. A qualitative research approach was used in order to design the potential clinical tools in response to specific feedback obtained from a nominal group. The nominal group consisted of pharmacists, three from the primary care pharmacists and one specialist pharmacist. Results — There were 21 patients’ pharmaceutical care plans included for analysis of care provided to 13 females (62%) and 8; males (38%). The mean age was 74 years (SD 10, range 51-88). COPD are present in 57% of the records (n=12), ischaemic heart failure in 43% (n=9), chronic heart failure in 33% (n=7), chronic kidney disease 33% (n=7), depression in 29% (n=6), myocardial infarction in 29% (n=6), hypertension in 29% (n=6), and diabetes type 2 in 24% (n=5). There were 127 pharmaceutical care issues identified, an mean of 6 care issues per person. Checks accounted for 46 (36%), and there were 65 (51%) changes in drug therapy, and 16 (13%) changes in drug therapy process. The most common drug therapy problem was inappropriate compliance in 35% (n=23) out of all drug therapy problems identified (n=65). The database was face validated by the nominal group and is fit for purpose. Discussion — The population of the database toolkit was done to demonstrate the functionality of reporting important outcomes from the pilot. For further work it is possible to link disease, medications, and pharmaceutical care issues, which will produce reports indicating the kind of medications or diseases / co-morbidities that are generating most problems. The database is fit for purpose and can be used for further evaluating the medication reviews conducted by pharmacists. It can also be a teaching tool for use during pharmacy education. URI: http://hdl.handle.net/10037/2209 File(s) in this item: 1
thesis.pdf (1.874Mb) -
Skurtveit, Svetlana; Bramness, Jørgen; Buajordet, Ingebjørg (Journal article; Tidsskriftartikkel; Peer reviewed, 2008)[+][-]
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Skurtveit, Svetlana; Engeland, Anders; Bramness, Jørgen G.; Mørland, Jørg (Journal article; Tidsskriftartikkel; Peer reviewed, 2008)[+][-]
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Skurtveit, Svetlana; Bachs, Liliana Casulleras; Bramness, Jørgen G.; Engeland, Anders (Journal article; Tidsskriftartikkel; Peer reviewed, 2008)[+][-]
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Sletvold, H; Johnsen, PJ; Wikmark, Odd-Gunnar; Simonsen, Gunnar Skov; Sundsfjord, A; Nielsen, KM (Journal article; Tidsskriftartikkel; Peer reviewed, 2010)[+][-]
Abstract: o determine the genetic composition of the first VanA-type plasmid (pIP816) reported, which was isolated from a clinical Enterococcus faecium (BM4147) strain in France in 1986, and to reveal the genetic units responsible for the dissemination of the vanA gene cluster by comparisons with current, published and additionally generated vanA-spanning plasmid sequences obtained from a heterogeneous E. faecium strain collection (n = 28).Plasmid sequences were produced by shotgun sequencing using ABI dye chemistry and primer walking, and were subsequently annotated. Comparative sequence analysis of the vanA region was done with published plasmids, with a partial vanA plasmid (pVEF4) reported here and to >140 kb of sequence obtained from a collection of vanA-harbouring plasmid fragments. Bioinformatic analyses revealed that pIP816 from 1986 and contemporary vanA plasmids shared a conserved genetic fragment of 25 kb, spanning the 10.85 kb vanA cluster encoded by Tn1546, and that the larger unit is present in both clinical and animal complexes of E. faecium. A new group II intron in pVEF4 was characterized. Comparative DNA analyses suggest that Tn1546 disseminates in and between clonal complexes of E. faecium as part of a larger genetic unit, possibly as a composite transposon flanked by IS1216 elements. URI: http://hdl.handle.net/10037/4124 File(s) in this item: 1
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Slipicevic, Ana; Holm, Ruth; Emilsen, Elisabeth; Rosnes, Anne Katrine Ree; Welch, Danny R.; Mælandsmo, Gunhild; Flørenes, Vivi Ann (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)[+][-]
Abstract: Breast cancer metastasis suppressor 1 (BRMS1) blocks metastasis in melanoma xenografts; however, its usefulness as a biomarker in human melanomas has not been widely studied. The goal was to measure BRMS1 expression in benign nevi, primary and metastatic melanomas and evaluate its impact on disease progression and prognosis. Paraffin-embedded tissue from 155 primary melanomas, 69 metastases and 15 nevi was examined for BRMS1 expression using immunohistochemistry. siRNA mediated BRMS1 down-regulation was used to study impact on invasion and migration in melanoma cell lines. A significantly higher percentage of nevi (87%), compared to primary melanomas (20%) and metastases (48%), expressed BRMS1 in the nucelus (p < 0.0001). Strong nuclear staining intensity was observed in 67% of nevi, and in 9% and 24% of the primary and metastatic melanomas, respectively (p < 0.0001). Comparable cytoplasmic expression was observed (nevi; 87%, primaries; 86%, metastases; 72%). However, a decline in cytoplasmic staining intensity was observed in metastases compared to nevi and primary tumors (26%, 47%, and 58%, respectively, p < 0.0001). Score index (percentage immunopositive celles multiplied with staining intensity) revealed that high cytoplasmic score index (≥ 4) was associated with thinner tumors (p = 0.04), lack of ulceration (p = 0.02) and increased disease-free survival (p = 0.036). When intensity and percentage BRMS1 positive cells were analyzed separately, intensity remained associated with tumor thickness (p = 0.024) and ulceration (p = 0.004) but was inversely associated with expression of proliferation markers (cyclin D3 (p = 0.008), cyclin A (p = 0.007), and p21Waf1/Cip1 (p = 0.009)). Cytoplasmic score index was inversely associated with nuclear p-Akt (p = 0.013) and positively associated with cytoplasmic p-ERK1/2 expression (p = 0.033). Nuclear BRMS1 expression in ≥ 10% of primary melanoma cells was associated with thicker tumors (p = 0.016) and decreased relapse-free period (p = 0.043). Nuclear BRMS1 was associated with expression of fatty acid binding protein 7 (FABP7; p = 0.011), a marker of invasion in melanomas. In line with this, repression of BRMS1 expression reduced the ability of melanoma cells to migrate and invade in vitro. Our data suggest that BRMS1 is localized in cytoplasm and nucleus of melanocytic cells and that cellular localization determines its in vivo effect. We hypothesize that cytoplasmic BRMS1 restricts melanoma progression while nuclear BRMS1 possibly promotes melanoma cell invasion. URI: http://hdl.handle.net/10037/4904 File(s) in this item: 1
article.pdf (1.334Mb) -
Stafne, Bente Helene (Master thesis; Mastergradsoppgave, 20-May-2009)[+][-]
Abstract: Forbruket av legemidler hos mennesker og dyr øker stadig, og som en konsekvens av dette, skilles mer legemidler ut, og ender opp i miljøet, og kan ende opp i sjøvann, jord og drikkevann til slutt. Legemidler kan ha toksiske effekter på andre organismer enn dem de er ment for, særlig siden legemidlene ikke er designet for å brytes hurtig ned. Enkelte ikke-steroide antiinflammatoriske legemidler (NSAIDs) med noen metabolitter ble valgt ut, i et forsøk på å påvise disse legemidlene i sjø- og avløpsvann på Svalbard og i Tromsø. Det ble utviklet en væske-væske mikroekstraksjonsmetode for å ekstrahere prøvene, samt en analysemetode ved hjelp av UPLC-MS/MS. Resultatene viste at noen av legemidlene ble påvist i sjøvann, dog ingen i kvantifiserbare konsentrasjoner, mens i avløpsvann ble det kvantifisert de fire legemidlene og en av metabolittene. Det var naturlig nok høyere konsentrasjoner i avløpsprøvene fra Tromsø enn i Longyearbyen, folketallet tatt i betraktning. Den samme metoden ble også benyttet til et UV-forsøk over 15 dager, der det ble undersøkt hvorvidt de analyserte legemidlene brytes ned i UV-lys sammenlignet med en kontrolløsning i mørket. Det legemidlet som det selges mest av, ibuprofen, ble ikke brutt ned i UV-lys, mens både naproxen, ketoprofen og diklofenak ble brutt ned, mens kontrolløsningene ikke ble brutt ned for noen stoffer. Det kunne ikke påvises noen av de undersøkte metabolittene, hvilket tyder på at de undersøkte metabolittene ikke dannes under UV-nedbrytning. URI: http://hdl.handle.net/10037/2198 File(s) in this item: 1
thesis.pdf (15.52Mb) -
Starikova, Irina; Harms, Klaus; Haugen, Pål; Lunde, Tracy Munthali; Primicerio, Raul; Samuelsen, Ørjan; Nielsen, Kaare Magne; Johnsen, Pål Jarle (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)[+][-]
Abstract: Horizontal gene transfer (HGT) plays a major role in bacterial microevolution as evident from the rapid emergence and spread of antimicrobial drug resistance. Few studies have however addressed the population dynamics of newly imported genetic elements after HGT. Here, we show that newly acquired class-1 integrons from Salmonella enterica serovar Typhimurium and Acinetobacter baumannii, free of associated transposable elements, strongly reduce host fitness in Acinetobacter baylyi. Insertional inactivation of the integron intI1 restored fitness, demonstrating that the observed fitness costs were due to the presence of an active integrase. The biological cost of harboring class-1 integrons was rapidly reduced during serial transfers due to intI1 frameshift mutations leading to inactivated integrases. We use a mathematical model to explore the conditions where integrons with functional integrases are maintained and conclude that environmental fluctuations and episodic selection is necessary for the maintenance of functional integrases. Taken together, the presented data suggest a trade-off between the ability to capture gene cassettes and long-term stability of integrons and provide an explanation for the frequent observation of inactive integron-integrases in bacterial populations. URI: http://hdl.handle.net/10037/4776 File(s) in this item: 1
article.pdf (288.7Kb)
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