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  • 1.
    Andersson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    TaqMan® Sample-to-SNP Kit™: evaluation of kit for low-cost and fast preparing of DNA-samples before genotype analysis2009Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

     

    Genotyping can be used to link genetic variation among individuals to certain diseases or conditions. Some known disorders and states that are dependent on single nucleotide polymorphism (SNPs) are lactose intolerance, venous thrombosis, hereditary hemochromatosis and the difference in sensibility among people to metabolise drugs.

    In this project a new kit, TaqManÒ Sample-to-SNP KitÔ for extraction of DNA and preparation of the extract for genotyping with real-time PCR and allelic discrimination, was evaluated. QIAamp® DNA Blood Biorobot® MDx Kit was used as the reference method.

    The purpose of the comparison was to find a method that makes DNA extraction from blood samples cheaper and faster, but with the same reliability as the reference procedure.

    The results of the evaluation showed a complete agreement of the genotype results between the methods tested, which means that the new method was as reliable as the reference method. The costs of reagents and material would be reduced with 52% if the new method is adopted, that alone would result in a cost reduction of 144 000SEK a year with a sample volume of 650 samples/month. The time for DNA extraction would also be reduced with the new procedure.

     

  • 2. Antonelli, Massimo
    et al.
    Bonten, Marc
    Cecconi, Maurizio
    Chastre, Jean
    Citerio, Giuseppe
    Conti, Giorgio
    Curtis, J Randall
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Joannidis, Michael
    Macrae, Duncan
    Maggiore, Salvatore M
    Mancebo, Jordi
    Mebazaa, Alexandre
    Preiser, Jean-Charles
    Rocco, Patricia
    Timsit, Jean-François
    Wernerman, Jan
    Zhang, Haibo
    Year in review in Intensive Care Medicine 2012: I. Neurology and neurointensive care, epidemiology and nephrology, biomarkers and inflammation, nutrition, experimentals2013In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 39, no 2, 232-246 p.Article, review/survey (Refereed)
  • 3.
    Asif, Sana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Jonsson, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden..
    Teramura, Yuji
    Univ Tokyo, Dept Bioengn, Tokyo, Japan..
    Gustafson, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Ekdahl, Kristina N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden..
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Conjugation of human recombinant CD39 to primary human hepatocytes protects against thromboinflammation2015In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, S87-S87 p.Article in journal (Other academic)
  • 4. Aspelund, Aleksanteri
    et al.
    Tammela, Tuomas
    Antila, Salli
    Nurmi, Harri
    Leppanen, Veli-Matti
    Zarkada, Georgia
    Stanczuk, Lukas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    Francois, Mathias
    Mäkinen, Taija
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    Saharinen, Pipsa
    Immonen, Ilkka
    Alitalo, Kari
    The Schlemm's canal is a VEGF-C/VEGFR-3-responsive lymphatic-like vessel2014In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 124, no 9, 3975-3986 p.Article in journal (Refereed)
    Abstract [en]

    In glaucoma, aqueous outflow into the Schlemm's canal (SC) is obstructed. Despite striking structural and functional similarities with the lymphatic vascular, system, it is unknown whether the SC is a blood or lymphatic vessel. Here, we demonstrated the expression of lymphatic endothelial cell markers by the SC in murine and zebrafish models as well as in human eye tissue. The initial stages of SC development involved induction of the transcription factor PROX1 and the lymphangiogenic receptor tyrosine kinase VEGFR-3 in venous endothelial cells in postnatal mice. Using gene deletion and function-blocking antibodies in mice, we determined that the lymphangiogenic growth factor VEGF-C and its receptor, VEGFR-3, are essential for SC development. Delivery of VEGF-C into the adult eye resulted in sprouting, proliferation, and growth of SC endothelial cells, whereas VEGF-A obliterated the aqueous outflow system. Furthermore, a single injection of recombinant VEGF-C induced SC growth and was associated with trend toward a sustained decrease in intraocular pressure in adult mice. These results reveal the evolutionary conservation of the lymphatic-like phenotype of the SC, implicate VEGF-C and VEGFR-3 as critical regulators of SC lymphangiogenesis, and provide a basis for further studies on therapeutic manipulation of the SC with VEGF-C in glaucoma treatment.

  • 5.
    Babiker, Adil A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ronquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Nilsson Ekdahl, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Prostasome Involvement in the Development and Growth of Prostate Cancer2010In: The Open Prostate Cancer Journal, ISSN 1876-8229, Vol. 3, 1-13 p.Article, review/survey (Refereed)
    Abstract [en]

    Prostasomes are extracellularly occurring submicron, membrane-surrounded organelles produced by the epithelial cells of the prostate and present in semen after secretion. Even dedifferentiated prostate cancer cells have preserved their ability to produce and export prostasomes to the extracellular space. The precise physiological role of prostasomes is not known, although some of their properties assign them to important physiological and patho-physiological functions that could be exploited in prostate cancer growth and development. In this review, some new properties of seminal and malignant cell line (DU145, PC-3 and LNCaP) prostasomes will be discussed.

    There are typical differences in the expressions and activities of prostasomal CD59, ATPase, protein kinases and tissue factor (TF) as well as in the transfer of prostasomal CD59 to CD59-deficient erythrocytes (rabbit and human PNH erythrocytes). CD59, protein kinases and TF exhibit characteristic patterns of overexpression by malignant cell prostasomes. A high ATPase activity is recognized on seminal prostasomes with minimal activity on malignant cell prostasomes resulting in more residual ATP available for phosphorylation reactions. Several proteins are phosphorylated by prostasomal protein kinases, namely, complement component C3, fibrinogen, vitronectin and E-cadherin. Furthermore, TF is identified as the main endogenous phosphorylation substrate on prostasomes. In addition, prothrombotic effects of prostasomes are demonstrated. DU145 and PC-3 cell-derived prostasomes exert a higher clotting effect on whole blood and plasma compared to LNCaP cell-derived and seminal prostasomes.

    In conclusion, malignant cell prostasomes show an increased ability to interact with the biological system in favor of prostate cancer cell promotion and survival. The roles played by prostasomes in this context may improve the understanding of the mechanisms that help the prostate cancer cells to avoid the complement attack (CD59 transfer and phosphorylation and inactivation of C3), to promote angiogenesis (TF) and to metastasize. It may also provide a better understanding of some of the complications usually seen in some terminal prostate cancer patients like thrombotic events and tendency to develop disseminated intravascular coagulation.

  • 6. Baskurt, Oguz
    et al.
    Boynard, Michel
    Cokelet, Giles
    Connes, Philippe
    Cooke, Brian M.
    Forconi, Sandro
    Liao, Fulong
    Hardeman, Max
    Jung, Friedrich
    Meiselman, Herbert
    Nash, Gerard
    Nemeth, Norbert
    Neu, Björn
    Sandhagen, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Shin, Sehyun
    Thurston, George
    Wautier, Jean Luc
    New guidelines for hemorheological laboratory techniques2009In: Clinical hemorheology and microcirculation, ISSN 1386-0291, E-ISSN 1875-8622, Vol. 42, no 2, 75-97 p.Article in journal (Refereed)
    Abstract [en]

    This document, supported by both the International Society for Clinical Hemorheology and the European Society for Clinical Hemorheology and Microcirculation, proposes new guidelines for hemorheological methods used in experimental and clinical studies. It is based on a similar document entitled: "Guidelines for measurement of blood viscosity and erythrocyte deformability" published in 1986 by the Expert Panel on Blood Rheology of the International Committee for Standardization in Hematology. Recent methods techniques and instruments, as well as new approaches to interpretation of results, are added to these new guidelines; wide spread adoption should improve comparability between hemorheological laboratories and increase the reliability of rheological tests.

  • 7.
    Biglarnia, Alireza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Yamamoto, Shinji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Sedigh, Amir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Drachenberg, Cinthia
    Univ Maryland Hosp, Dept Pathol, Baltimore, MD 21201 USA..
    Wagner, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Sund, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Berglund, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    von Zur-Muehlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Impact of duodenal cuff inflammation on outcome after clinical pancreas transplantation - a survey of a comprehensive follow-up strategy including serial protocol biopsy of the duodenal cuff2015In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, S15-S15 p.Article in journal (Other academic)
  • 8. Bischoff, Stephan C
    et al.
    Singer, Pierre
    Koller, Michael
    Barazzoni, Rocco
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    van Gossum, André
    Standard operating procedures for ESPEN guidelines and consensus papers2015In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 34, no 6, 1043-1051 p.Article in journal (Refereed)
    Abstract [en]

    The ESPEN Guideline standard operating procedures (SOP) is based on the methodology provided by the Association of Scientific Medical Societies of Germany (AWMF), the Scottish Intercollegiate Guidelines Network (SIGN), and the Centre for Evidence-based Medicine at the University of Oxford. The SOP is valid and obligatory for all future ESPEN-sponsored guideline projects aiming to generate high-quality guidelines on a regular basis. The SOP aims to facilitate the preparation of guideline projects, to streamline the consensus process, to ensure quality and transparency, and to facilitate the dissemination and publication of ESPEN guidelines. To achieve this goal, the ESPEN Guidelines Editorial board (GEB) has been established headed by two chairmen. The GEB will support and supervise the guideline processes and is responsible for the strategic planning of ESPEN guideline activities. Key elements of the SOP are the generation of well-built clinical questions according to the PICO system, a systemic literature search, a classification of the selected literature according to the SIGN evidence levels providing an evidence table, and a clear and straight-forward consensus procedure consisting of online voting's and a consensus conference. Only experts who meet the obligation to disclosure any potential conflict of interests and who are not employed by the Industry can participate in the guideline process. All recommendations will be graded according to the SIGN grading and novel outcome models besides biomedical endpoints. This approach will further extent the leadership of ESPEN in creating up-to-date and suitable for implementation guidelines and in sharing knowledge on malnutrition and clinical nutrition.

  • 9.
    Bjuhr, Mathias
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Berne, Christian
    Department of Medical Sciences.
    Larsson, Anders
    Department of Medical Sciences.
    External Quality Assessment of HbA1c for Point of Care Testing2005Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Objectives: To evaluate the long term total imprecision of HbA1c testing within the county of Uppsala in relation to the Swedish analytical goal of coefficient of variation (CV) <3% for HbA1c and to study the cost of an external quality assurance program for point-of-care HbA1c The county uses Bayer DCA 2000™ for point-of care HbA1c testing currently having 23 of these instruments.

    Methods: Method imprecision was assessed by analysis of patient samples performed as split samples during a 3 year period (2002-2004) as part of the quality assurance program for point-of-care HbA1c testing. The samples were first analysed on a Bayer DCA 2000™ and the samples were then sent to the centralised laboratory for reanalysis with an HPLC system (Variant II™, Biorad). The testing was performed approximately 8 times per year with each instrument.

    Results: The median CV between the HPLC method and the point-of-care instruments for each unit was slightly higher than 3%.

    Conclusion: The DCA 2000™ systems have an acceptable imprecision and agreement with the central laboratory. The test results show acceptable agreements within the county regardless where the patient is tested. The cost of the external quality assurance program is calculated to be approximately SEK 1340 (Euro 150) per instrument.

  • 10.
    Blomberg, Hans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lundström, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Toss, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Johansson, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Agreement between ambulance nurses and physicians in assessing stroke patients2013In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 129, no 1, 49-55 p.Article in journal (Refereed)
    Abstract [en]

    Objectives: If an ambulance nurse could bypass the emergency department (ED) and bring suspected stroke patients directly to a CT scanner, time to thrombolysis could be shortened. This study evaluates the level of agreement between ambulance nurses and emergency physicians in assessing the need for a CT scan, and interventions and monitoring beforehand, in patients with suspected stroke and/or a lowered level of consciousness.

    Materials and Methods: From October 2008 to June 2009 we compared the ambulance nurses’ and ED physicians’ judgement of 200 patients with stroke symptoms . Both groups answered identical questions on patients’ need for a CT scan, and interventions and monitoring beforehand.  

    Results: There was a poor agreement between ambulance nurses and ED physicians in judging the need for a CT scan: κ = 0.22 (95% confidence interval (CI): 0.06–0.37). The nurses’ ability to select the same patients as the physician for a CT scan had a sensitivity of 84% (95% CI: 77–89) and a specificity of 37% (95% CI: 23–53). Agreement concerning the need for interventions and monitoring was also low: κ = 0.32 (95% CI: 0.18–0.47). In 18% of cases, the nurses considered interventions before a CT scan unnecessary when the physicians’ deemed them necessary.

    Conclusions: Additional tools to support ambulance nurses decisions appear to be required before suspected stroke patients can be taken directly to a CT scanner.

     

     

  • 11.
    Carlsson, Josefine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Kartläggning av diskrepanser i ordinationslistan med hjälp av en klinisk farmaceut på infektionsavdelningar på Danderyds sjukhus2017Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Abstract

    Background and objective: It is essential to have a correct medication list when admitted to the hospital. A correct medication list enables a correct assessment of a patient’s condition. The aim of this study was to identify medication errors in the electronic medical record at infection wards at Danderyd Hospital. The secondary aim was to evaluate if gender, age or use of medication dispensing system influences the number of medication errors.

     

    Design: Medication reconcillation was performed by a clinical pharmacist at three infection wards during a five week period. The number of errors were calculated and classified as either wrong dose, omitted drug, drug not currently in use or duplicate therapy. Unpaired t-tests were used to compare the number of medication errors between gender and use of medication dispensing system. An ANOVA-test was used to compare the number of medication errors between different groups of ages.

     

    Setting: Three infection wards at Danderyd Hospital, Stockholm.

     

    Main outcome measures: The number of medication lists with at least one medication error, the mean value of medication errors among all patients and in different groups of patients.

     

    Results: The number of identified medication errors were 175 among 85 patients. The mean value was 2,1 ± 2,5 medication errors/patient and 64 % of the patients had at least one medication error. Most medication errors were classified as drug not currently in use followed by wrong dose. There were no significant differences between number of errors and gender (p=0,94); age (p=0,054) or use of medication dispensing system (p=0,84).

     

    Conclusions: The proportion of patients with at least one medication error were 64 % and the mean value was 2,1 ± 2,5 medication errors/patient. These results indicates that it is necessary to do a medication reconcilliation after admission to these wards, which a clinical pharmacist could help with.

     

  • 12.
    Cederholm, Tommy
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Bosaeus, Ingvar
    Brunner, Robert
    Ellegård, Lars
    Faxén Irving, Gerd
    Larsson, Jörgen
    Thorell, Anders
    Rothenberg, Elisabeth
    SBU-rapport "missar" övertygande evidensläge: Kosttillägg förlänger livet på undernärda äldre2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 51-52, 2299-2300 p., C7YMArticle in journal (Refereed)
    Abstract [sv]

    Tvärtemot slutsatserna i en ny SBU-rapport anser Tommy Cederholm och medförfattare att det finns övertygande ­evidens för att kosttillägg är gynnsamt för undernärda äldre. Ordination ska dock ske först efter utredning, ­göras patientsäkert, dokumenteras och utvärderas ­individuellt.

  • 13. Cook, Jackie
    et al.
    Aydin-Schmidt, Berit
    Gonzalez, Iveth J.
    Bell, David
    Edlund, Elin
    Nassor, Majda H.
    Msellem, Mwinyi
    Ali, Abdullah
    Abass, Ali K.
    Mårtensson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Bjorkman, Anders
    Loop-mediated isothermal amplification (LAMP) for point-of-care detection of asymptomatic low-density malaria parasite carriers in Zanzibar2015In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 14, 43- p.Article in journal (Refereed)
    Abstract [en]

    Background: Asymptomatic, low parasite density malaria infections are difficult to detect with currently available point-of-care diagnostics. This study piloted a loop-mediated isothermal amplification (LAMP) kit for field-friendly, high-throughput detection of asymptomatic malaria infections during mass screening and treatment (MSAT) in Zanzibar, a malaria pre-elimination setting. Methods: Screening took place in three known hotspot areas prior to the short rains in November. Finger-prick blood was taken for screening by rapid diagnostic test (RDT) and LAMP and collected on filter paper for subsequent polymerase chain reaction (PCR) analyses. LAMP results were compared to RDT and to PCR using McNemar's test. Results: Approximately 1,000 people were screened. RDT detected ten infections (1.0% (95% CI 0.3-1.6)) whilst both LAMP and PCR detected 18 (1.8% (95% CI 0.9-2.6)) infections. However, PCR identified three infections that LAMP did not detect and vice versa. LAMP testing was easy to scale-up in field conditions requiring minimal training and equipment, with results ready one to three hours after screening. Conclusions: Despite lower than expected prevalence, LAMP detected a higher number of infections than the currently used diagnostic, RDT. LAMP is a field-friendly, sensitive diagnostic test that could be useful for MSAT malaria campaigns which require quick results to enable prompt treatment.

  • 14. Cruz-Jentoft, A J
    et al.
    Boirie, Y
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Re: Issues concerning sarcopenia in ageing adults2015In: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 44, no 2, 343-344 p.Article in journal (Refereed)
  • 15.
    Dehmer, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Validation of Abbott Diagnostics turbidimetric cystatin C assay and enzymatic creatinine assay using the Architect c8000 analyzer2009Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Objective: Estimation of glomerular filtration rate (GFR) is an important tool in the diagnosis and management of chronic kidney disease. Today creatinine is the most frequently used marker for kidney function though several studies indicate that cystatin C is a superior marker. The purpose of this study was to validate Abbott Diagnostics turbidimetric cystatin C assay and enzymatic creatinine assay.

    Methods: The validation was performed by studies of CV for the two methods and correlations between the two and other available methods for assessing GFR. The stability of cystatin C at room temperature was also evaluated.

    Results: Both methods showed good precision. The Abbott cystatin C assay generally gave lower values and thereby higher estimated GFRs than the correlated Gentian method. The Abbott enzymatic creatinine assay gave higher values than the correlated Jaffe method. Those results are generally unexpected, but in this study the cause is an automatically applied negative intercept used together with the Jaffe method. Cystatin C showed high stability when stored at room temperature.

    Conclusions: Estimated GFRs tend to differ depending on the choice of method for analyzing cystatin C or creatinine and this study gives an overview of the range of variation. The study also enlightens the need for an international calibrator for the cystatin C methods presented by different manufacturers.

  • 16.
    Edblom, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    A Comparison of Two Immunoturbidimetric Assay Methods for Serum Amyloid A in Cats.2011Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The analysis of acute phase protein serum amyloid A (SAA) has recently been brought into clinical use in veterinary medicine. Some of the difficulties with incorporating the SAA method in clinical practice have been the expensive and rather large equipment required for the method. Due to these difficulties only larger clinics can afford to use the SAA analysis.

    The company Equinostic has recently developed a smaller instrument that costs one-tenth of a larger instrument. The instrument is named EVA1 and has so far only been used to analyze SAA in horses.

    The aim of this study was to investigate if the EVA1 instrument could be used to analyze SAA in cats. This study included 24 serum samples from cat, which were first analyzed twice on the EVA1 instrument and then sent to the Strömsholm Referral Animal Hospital in Sweden where they reanalyzed the samples using a validated reference method. Both instruments are based on an immunoturbidimetric assay.

    The correlation between the two instruments was good (r=0.97) but the EVA1 instrument showed constantly lower results than the reference method. The difference between the duplicates when analyzed on the EVA1 instrument was larger than expected.

    The conclusion is that EVA1 could be used to analyze SAA in cats. However, before it could be used clinically in veterinary practice an extended study is recommended.

  • 17. ElShafie, Amir Ibrahim
    et al.
    Elghazali, Gehad
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cystatin C as a marker of immune complex-associated renal impairment in a sudanese population with visceral leishmaniasis2006In: American Journal of Tropical Medicine and Hygiene, ISSN 0002-9637, E-ISSN 1476-1645, Vol. 75, no 5, 864-868 p.Article in journal (Refereed)
    Abstract [en]

    Renal function was studied in visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL) by means of the specific marker cystatin C and related to circulating immune complexes and cytokine production. Forty patients with VL (23 with sub-acute disease and 17 with acute disease), 17 patients with PKDL, and 22 healthy controls were included. Cystatin C, but not creatinine, was significantly raised in VL (P = 0.004). The highest levels of cystatin C were found in those with acute disease (P < 0.0001). In VL, cystatin C levels were positively correlated to circulating immune complexes and production of granulocyte-macrophage colony stimulating factor (GM-CSF), but negatively correlated to aspartate aminotransferase and lactate dehydrogenase. We conclude that cystatin C is a superior marker of glomerular function in leishmaniasis and that immune complex deposition and GM-CSF are two functions that most likely are causally involved in the mechanisms leading to glomerular dysfunction in leishmaniasis.

  • 18.
    Florvall, Gösta
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Basu, Samar
    Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Helmersson, Johanna
    Department of Public Health and Caring Sciences, Clinical Nutrition Research.
    Larsson, Anders
    Department of Medical Sciences.
    Microalbuminuria, blood pressure and cardiovascular risk factors in elderly males2005Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Objective - To correlate blood pressure and inflammatory markers with urine albumin analysed with a point-of-care testing (POCT) instrument, nephelometric determination of albumin and creatinine related urine albumin in elderly males.

    Methods and Results - The study population consisted of 103 diabetic and 603 nondiabetic males (age 77 years) in a cross-sectional study in central Sweden. We analyzed urine albumin with a HemoCue® Urine Albumin POCT instrument and a ProSpec® nephelometer and creatinine related urine albumin. There were strong correlation between both systolic and diastolic blood pressure and all three urine albumin methods (p<0.0001). There were also significant correlations between the different urine albumin measurements and SAA, hsCRP and IL-6.

    Conclusions - Hypertension has a strong impact on hyperfiltration in diabetic and nondiabetic elderly males.

  • 19.
    Fred, Rikard G.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Boddeti, Santosh Kumar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lundberg, Marcus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Welsh, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Imatinib mesylate stimulates low-density lipoprotein receptor-related protein 1-mediated ERK phosphorylation in insulin-producing cells2015In: Clinical Science, ISSN 0143-5221, E-ISSN 1470-8736, Vol. 128, no 1, 17-28 p.Article in journal (Refereed)
    Abstract [en]

    Low-density lipoprotein receptor-related protein 1 (LRP1) is an endocytic and multi-functional type I cell surface membrane protein, which is known to be phosphorylated by the activated platelet-derived growth factor receptor (PDGFR). The tyrosine kinase inhibitor imatinib, which inhibits PDGFR and c-Abl, and which has previously been reported to counteract beta-cell death and diabetes, has been suggested to reduce atherosclerosis by inhibiting PDGFR-induced LRP1 phosphorylation. The aim of the present study was to study LRP1 function in beta-cells and to what extent imatinib modulates LRP1 activity. LRP1 and c-Abl gene knockdown was performed by RNAi using rat INS-1 832/13 and human EndoC1-beta H1 cells. LRP1 was also antagonized by treatment with the antagonist low-density lipoprotein receptor-related protein associated protein 1 (LRPAP1). We have used PDGF-BB, a PDGFR agonist, and apolipoprotein E (ApoE), an LRP1 agonist, to stimulate the activities of PDGFR and LRP1 respectively. Knockdown or inhibition of LRP1 resulted in increased hydrogen peroxide (H2O2)(-) or cytokine-induced cell death, and glucose-induced insulin release was lowered in LRP1-silenced cells. These results indicate that LRP1 function is necessary for beta-cell function and that LRP1 is adversely affected by challenges to beta-cell health. PDGF-BB, or the combination of PDGF-BB+ApoE, induced phosphorylation of extracellular-signal-regulated kinase (ERK), Akt and LRP1. LRP1 silencing blocked this event. Imatinib blocked phosphorylation of LRP1 by PDGFR activation but induced phosphorylation of ERK. LRP1 silencing blocked imatinib-induced phosphorylation of ERK. Sunitinib also blocked LRP1 phosphorylation in response to PDGF-BB and induced phosphorylation of ERK, but this latter event was not affected by LRP1 knockdown. siRNA-mediated knockdown of the imatinib target c-Abl resulted in an increased ERK phosphorylation at basal conditions, with no further increase in response to imatinib. Imatinib-induced cell survival of tunicamycin-treated cells was partially mediated by ERK activation. We have concluded that imatinib promotes LRP1-dependent ERK activation, possibly via inhibition of c-Abl, and that this could contribute to the pro-survival effects of imatinib on beta-cells.

  • 20. Glimåker, Martin
    et al.
    Lindquist, Lars
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Lumbar puncture in adult bacterial meningitis: time to reconsider guidelines?2013In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 346, f361Article in journal (Refereed)
  • 21.
    Goto, Masafumi
    et al.
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan.;Tohoku Univ, Div Adv Surg Sci & Technol, Sendai, Miyagi 980, Japan..
    Friberg, Andrew
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ståhle, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Imura, Takehiro
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan..
    Yamagata, Youhei
    Tokyo Univ Agr & Technol, Dept Appl Biol Chem, Tokyo, Japan..
    Watanabe, Kimiko
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan..
    Murayama, Kazutaka
    Tohoku Univ, Div Biomed Measurements & Diagnost, Sendai, Miyagi 980, Japan..
    Inagaki, Akiko
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan..
    Igarashi, Yasuhiro
    Tohoku Univ, New Ind Creat Hatchery Ctr, Sendai, Miyagi 980, Japan..
    Satomi, Susumu
    Tohoku Univ, Div Adv Surg Sci & Technol, Sendai, Miyagi 980, Japan..
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Proof of concept for the clinical application of animal component free recombinant collagenase for isolating pancreatic islets2015In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, S50-S50 p.Article in journal (Other academic)
  • 22.
    Grapensparr, Liza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Intracardially injected neural crest stem cells home to the pancreas and delays disease progression in an animal model for type 1 diabetes2015In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, S198-S199 p.Article in journal (Other academic)
  • 23.
    Hamberg, Anna-Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Hellman, Jacob
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Dahlberg, Jonny
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Jonsson, E Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Wadelius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    A Bayesian decision support tool for efficient dose individualization of warfarin in adults and children2015In: BMC Medical Informatics and Decision Making, ISSN 1472-6947, E-ISSN 1472-6947, Vol. 15, no 7Article in journal (Refereed)
    Abstract [en]

    Warfarin is the most widely prescribed anticoagulant for prevention and treatment of thromboembolic events. Although highly effective, the use of warfarin is limited by a narrow therapeutic range combined with a more than ten-fold difference in the dose required for adequate anticoagulation in adults. For each patient, an optimal dose that leads to a favourable balance between the wanted antithrombotic effect and the risk of bleeding, measured as the prothrombin time International Normalised Ratio (INR), must be found. A model capable of describing the time-course of the INR response to warfarin therapy can be used to aid dose selection, both before starting therapy (a priori dose prediction) and after therapy has been initiated (a posteriori dose revision). In this paper we describe the transfer of a population PKPD-model for warfarin developed in NONMEM to a platform independent decision support tool written in Java. The tool proved capable of solving a system of differential equations representing the pharmacokinetics and pharmacodynamics of warfarin, with a performance comparable to NONMEM. To estimate an a priori dose the user provides information on body weight, age, CYP2C9 and VKORC1 genotype, baseline and target INR. With addition of information about previous doses and INR observations, the tool will use a Bayesian forecasting method to suggest an a posteriori dose, i.e. the dose with the highest probability to result in the desired INR. Results are displayed as the predicted dose per day and per week, and graphically as the predicted INR curve. The tool can also be used to predict INR following any given dose regimen, e.g. a loading-dose regimen. We believe it will provide a clinically useful tool for initiating and maintaining warfarin therapy in the clinic. It will ensure consistent dose adjustment practices between prescribers, and provide more efficient individualization of warfarin dosing in both children and adults.

  • 24.
    Hellman, Jana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Comparison of Different Electrophoretic Methods for Haptoglobin Phenotyping and an Investigation in Patients with Abdominal Aortic Aneurysm2011Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Haptoglobin is an acute phase protein with important biological role because of its capacity to bind to haemoglobin. Haptoglobin exists in three major genetic polymorphism types: Hp1-1, Hp2-1 and Hp2-2, the distribution of which has been associated with abdominal aortic aneurysm (AAA), an asymptomatic aortic disease common among men older than 65 years.    Five different electrophoretic methods were tested according to their ability to separate the haptoglobin phenotypes. The detection was based on a produced hemolysate of blood in which haemoglobin binds to haptoglobin thereby forming a complex that can be detected by specific haemoglobin staining using TMB-dihydrochloride and hydro peroxide as substrate resulting in an azure-green color of the bands. Samples from 15 patients who had suffered surgery for not broken AAA, that is more than5.0 cmaortic diameter, and 15 samples from matched controls were analyzed.    Among the five tested electrophoretic methods best migration and separation was seen on the pre-cast agarosgel Hydragel HR on the instrument Hydrasys. The other four methods gave less successful results. This pilot investigation showed the following distribution of the phenotypes of haptoglobin among AAA patients; 7 % Hp1-1, 40 % Hp2-1 and 53 % Hp2-2 and for the controls; 13 % Hp1-1, 33 % Hp2-1 and 53 % Hp2-2.    In conclusion, the used techniques has to be further optimized and more patients have to be included in the study before it can be ascertained if the phenotypes of Haptoglobin play any role in the progress of the AAA disease.

  • 25.
    Hikmet Noraddin, Feria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Measurement and validation of urinary cystatin C by particle-enhanced turbidimetric immunoassay on Architect ci82002011Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Cystatin C, a 13 kDa low molecular weight protein is an inhibitor of cysteine proteases. Due to its low molecular weight and positive charge at physiological pH, it is freely filtered by the glomerulus and catabolized after reabsorption by proximal tubular cells with a low concentration (0.03-0.3 mg/L) in urine amongst healthy subjects. Urinary cystatin C is a potential biomarker detection of acute kidney injury (AKI) in the acute phase when patients are submitted to the intensive care unit. The aim in this report was to perform a full method validation of urinary analysis of cystatin C on a high throughput chemical analyzer by particle-enhanced turbidimetric immunoassay (PETIA) at the University Hospital in Uppsala, Sweden. The antigen excess, linearity, lower limit of quantification (LoQ), recovery, assay precision, stability and interference caused by haemoglobin was evaluated. No hook effect was observed, the assay was linear over the studied interval <0.001-0.950 mg/L with a regression of R2=0.9994. The LoQ was calculated to 0.020 mg/L with a coefficient of variation (CV) ≤10% which was considered acceptable. The assay had a recovery between 93-100% and the assay precision had a total CV <3.5%. Cystatin C is stable for 3 days in room temperature and 14 days in +4C. The assay did not show any major interference with haemoglobin. The urinary cystatin C showed good precision and performance characteristics by measurements using PETIA all of which is a necessary qualification for a biomarker at a 24-h running routine laboratory.

  • 26.
    Jonsson, Susanne
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Comparison between four commonly used methods for detection of small M-components in plasma2008Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Analysis of M-components is an important part of the diagnosis of monoclonal gammopathies and for the evaluation of disease response during treatment. In this project, two widely used electrophoresis methods and their corresponding immunotyping method were compared to evaluate the sensitivity of each method for the detection of small M-components. The project included 30 plasma samples from patients with identified M-components; 10 samples containing each IgG, IgA and IgM, respectively. All samples were diluted with normal EDTA plasma to achieve M-components of 5,00g/L. The samples were then serially diluted to achieve M-component concentrations of; 5,00, 2,50, 1,25, 0,63, 0,31 and 0,16g/L. All 180 samples were analysed with agarose gel electrophoresis and capillary electrophoresis. The dilutions above and below the detection level of each method were then analysed with immunofixation and immunosubtraction. The results showed good agreement between agarose gel electrophoresis and capillary electrophoresis in the highest concentrations of IgG and IgM. With agarose gel electrophoresis, IgA was detected in the same location as transferrin and the lowest concentration detected were therefore 1,25g/L. Besides the samples containing IgG, immunofixation was the most sensitive method.

  • 27. Kaisdotter Andersson, Annika
    et al.
    Kron, Josefin
    Karolinska institutet.
    Castren, Maaret
    Karolinska institutet.
    Muntlin Athlin, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. School of Nursing, University of Adelaide.
    Hök, Bertil
    Wiklund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Assessment of the breath alcohol concentration in emergency care patients with different level of consciousness2015In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 23, no 1, 11Article in journal (Refereed)
    Abstract [en]

    Background

    Many patients seeking emergency care are under the influence of alcohol, which in many cases implies a differential diagnostic problem. For this reason early objective alcohol screening is of importance not to falsely assign the medical condition to intake of alcohol and thus secure a correct medical assessment.

    Objective

    At two emergency departments, demonstrate the feasibility of accurate breath alcohol testing in emergency patients with different levels of cooperation.

    Method

    Assessment of the correlation and ratio between the venous blood alcohol concentration (BAC) and the breath alcohol concentration (BrAC) measured in adult emergency care patients. The BrAC was measured with a breathalyzer prototype based on infrared spectroscopy, which uses the partial pressure of carbon dioxide (pCO2) in the exhaled air as a quality indicator.

    Result

    Eighty-eight patients enrolled (mean 45 years, 53 men, 35 women) performed 201 breath tests in total. For 51% of the patients intoxication from alcohol or tablets was considered to be the main reason for seeking medical care. Twenty-seven percent of the patients were found to have a BAC of <0.04 mg/g. With use of a common conversion factor of 2100:1 between BAC and BrAC an increased agreement with BAC was found when the level of pCO2 was used to estimate the end-expiratory BrAC (underestimation of 6%, r = 0.94), as compared to the BrAC measured in the expired breath (underestimation of 26%, r = 0.94). Performance of a forced or a non-forced expiration was not found to have a significant effect (p = 0.09) on the bias between the BAC and the BrAC estimated with use of the level of CO2. A variation corresponding to a BAC of 0.3 mg/g was found between two sequential breath tests, which is not considered to be of clinical significance.

    Conclusion

    With use of the expired pCO2 as a quality marker the BrAC can be reliably assessed in emergency care patients regardless of their cooperation, and type and length of the expiration.

  • 28.
    Klar, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hisatsune, Chihiro
    Baig, Shahid M.
    Tariq, Muhammad
    Johansson, Anna C. V.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Rasool, Mahmood
    Malik, Naveed Altaf
    Ameur, Adam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sugiura, Kotomi
    Feuk, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Mikoshiba, Katsuhiko
    Dahl, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Abolished InsP3R2 function inhibits sweat secretion in both humans and mice2014In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 124, no 11, 4773-4780 p.Article in journal (Refereed)
    Abstract [en]

    There are 3 major sweat-producing glands present in skin; eccrine, apocrine, and apoeccrine glands. Due to the high rate of secretion, eccrine sweating is a vital regulator of body temperature in response to thermal stress in humans; therefore, an inability to sweat (anhidrosis) results in heat intolerance that may cause impaired consciousness and death. Here, we have reported 5 members of a consanguineous family with generalized, isolated anhidrosis, but morphologically normal eccrine sweat glands. Whole-genome analysis identified the presence of a homozygous missense mutation in ITPR2, which encodes the type 2 inositol 1,4,5-trisphosphate receptor (InsP3R2), that was present in all affected family members. We determined that the mutation is localized within the pore forming region of InsP3R2 and abrogates Ca2+ release from the endoplasmic reticulum, which suggests that intracellular Ca2+ release by InsP3R2 in clear cells of the sweat glands is important for eccrine sweat production. Itpr2–/– mice exhibited a marked reduction in sweat secretion, and evaluation of sweat glands from Itpr2–/– animals revealed a decrease in Ca2+ response compared with controls. Together, our data indicate that loss of InsP3R2-mediated Ca2+ release causes isolated anhidrosis in humans and suggest that specific InsP3R inhibitors have the potential to reduce sweat production in hyperhidrosis.

  • 29. Koupil, I
    et al.
    Leon, D A
    Byberg, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Birth weight, hypertension and "white coat" hypertension: size at birth in relation to office and 24-h ambulatory blood pressure.2005In: J Hum Hypertens, ISSN 0950-9240, Vol. 19, no 8, 635-42 p.Article in journal (Refereed)
  • 30. Laguzzi, F
    et al.
    Alsharari, Zayed
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Vikström, M
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Gigante, B
    Hellénius, M-L
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Bottai, M
    de Faire, U
    Leander, K
    Cross-sectional relationships between dietary fat intake and serum cholesterol fatty acids in a Swedish cohort of 60-year-old men and women2016In: Journal of human nutrition and dietetics (Print), ISSN 0952-3871, E-ISSN 1365-277X, Vol. 29, no 3, 325-337 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The present study aimed to describe the relationship between self-reported dietary intake and serum cholesterol fatty acids (FAs) in a Swedish population of 60-year-old men and women.

    METHODS: Cross-sectional data collected in 1997-1998 from 4232 individuals residing in Stockholm County were used. Five diet scores were created to reflect the intake of saturated fats in general, as well as fats from dairy, fish, processed meat and vegetable oils and margarines. Gas chromatography was used to assess 13 FAs in serum cholesterol esters. The association between each diet score and specific FAs was assessed by percentile differences (PD) with 95% confidence intervals (CI) at the 10th, 25th, 50th, 75th and 90th percentile of each FA across levels of diet scores using quantile regression.

    RESULTS: Fish intake was associated with high proportions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). For each point increase in fish score, the 50th PD in EPA and DHA was 32.78% (95% CI = 29.22% to 36.35%) and 10.63% (95% CI = 9.52% to 11.74%), respectively. Vegetable fat intake was associated with a high proportion of linoleic acid and total polyunsaturated fatty acids (PUFA) and a low proportion of total saturated fatty acids (SFA). The intake of saturated fats in general and dairy fat was slightly associated with specific SFA, although the intake of fat from meat was not.

    CONCLUSIONS: In the present study population, using a rather simple dietary assessment method, the intake of fish and vegetable fats was clearly associated with serum PUFA, whereas foods rich in saturated fats in general showed a weak relationship with serum SFA. Our results may contribute to increased knowledge about underlying biology in diet-cardiovascular disease associations.

  • 31. Lampinen, Maria
    et al.
    Håkansson, Lena Douhan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Klinisk kemi.
    Venge, Per
    Klinisk kemi.
    Albumin stimulation of eosinophil migration involves PI3-kinases and is associated with diminished eosinophil CD49d and CD49f expression.2006In: Int Arch Allergy Immunol, ISSN 1018-2438, Vol. 140, no 2, 113-20 p.Article in journal (Refereed)
  • 32.
    Lampinen, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Carlson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Selective priming of peripheral blood eosinophils in patients with idiopathic hypereosinophilic syndrome2006In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 114, no 11, 757-763 p.Article in journal (Refereed)
    Abstract [en]

    The idiopathic hypereosinophilic syndrome (HES) is characterised by blood eosinophilia associated with organ involvement. Elevated numbers of blood neutrophils have been observed during episodes of active HES. However, an increased responsiveness of eosinophils to chemotactic and chemokinetic stimuli may explain the selective eosinophil infiltration of the tissue. We have studied the migratory responses of blood eosinophils and neutrophils from 9 patients with HES and from 13 healthy control subjects. Chemokinetic and chemotactic responses to factors acting on both cell types were analysed by means of a modification of the Boyden chamber technique. We found increased migratory responses of the eosinophils, but not of the neutrophils, from the patients with HES. Increased blood neutrophil counts in three of the patients did not coincide with alterations of the neutrophil migratory responses. Our finding of increased migratory responses of eosinophils from patients with HES towards non-specific chemoattractants suggests selective priming of eosinophils in this disease. Interleukin (IL)-5 has previously been shown to prime eosinophils for migratory responses, and successful anti-IL-5 therapy of patients with HES indicates an important role for this cytokine in the development of hypereosinophilia.

  • 33.
    Lannsjö, Marianne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    Clinical outcome and brain pathology after mild traumatic brain injury: an exploratory study by repeated MR examinationsManuscript (preprint) (Other academic)
  • 34.
    Lannsjö, Marianne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    Mild Traumatic Brain Injury: Studies on outcome and prognostic factors2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Objectives: To explore the prevalence and structure of self-reported disability after mild traumatic brain injury and the impact of traumatic brain pathology on such outcome.

    Material and methods: In study 1-3, symptoms data were collected by use of Rivermead Post-concussion Symptoms Questionnaire (RPQ) and data on global function by use of Glasgow Outcome Scale Extended (GOSE) from 2602 patients at 3 months after MTBI. RPQ data were subject to factor and Rasch-analyses Head CT data from 1262 patients were used in a prediction analysis that also included age and gender. In study 4, MRI and symptoms data were collected at 2-3 days and at 3-7 months follow-up after MTBI in 19 patients. Global function was assessed at follow-up by use of the Rivermead Head Injury Follow-Up Questionnaire (RHIFUQ) and GOSE.

    Results: I. Most respondents reported no remaining symptoms but 24% reported ≥3 and 10% ≥7 remaining symptoms. The factor analysis demonstrated that all symptoms are correlated but also identified subgroups of symptoms. II. Rasch-analysis of RPQ showed disordered category function, local dependency of items, poor targeting of persons to items and indications of 3 or more dimensions. There was no differential item functioning. III. Head CT pathology with no need for acute intervention was observed in 52 patients (4%) but was not associated with either frequency of remaining symptoms or global outcome at 3 months post injury. Female gender and age over 30 years were associated with less favourable outcome with respect to symptoms and GOSE. IV. Post-acute MRI indicated trauma-related pathology in one patient and follow-up MRI indicated loss of brain volume in 4 patients.

    Conclusions: A substantial proportion of patients with MTBI report remaining problems at three months after MTBI. RPQ is useful but not optimal to assess symptoms outcome after MTBI and calculation of a total sum score is not recommended. Female gender and older age are negative prognostic factors while brain pathology according to CT has no effect on self-reported outcome. Loss of brain volume after MTBI according to MRI may be a sensitive marker of traumatic brain pathology and deserves further studies.

    List of papers
    1. Prevalence and structure of symptoms at 3 months after mild traumatic brain injury in a national cohort
    Open this publication in new window or tab >>Prevalence and structure of symptoms at 3 months after mild traumatic brain injury in a national cohort
    Show others...
    2009 (English)In: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 23, no 3, 213-219 p.Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES

    To describe symptom prevalence and structure after mild traumatic brain injury (MTBI) in a population-based cohort.

    METHODS

    Symptoms data were collected at 3 months post-MTBI by use of the Rivermead Post-concussion Symptoms Questionnaire (RPQ) at follow-up of 2602 patients attending 39 Swedish hospitals. Spearmans rank correlation analysis was used to explore correlations between symptoms and structural equation modelling (SEM) was performed by use of several fit indices to explore if data were compatible with one or more factors.

    RESULTS

    Questionnaires were received from 2523 (97%) patients with a mean age of 31 years (median 22, range 6-96). A majority of the respondents (56%) reported no remaining injury related symptoms, 24% reported three or more symptoms and 10% reported seven or more symptoms. All symptoms exhibited strong positive inter-relations and SEM provided strong support for a single or two factor solution. Fit indices were only slightly weaker for three and four factor solutions.

    CONCLUSIONS

    A significant minority of patients reported multiple symptoms to persist at 3 months after MTBI. The observed structure of symptoms according to RPQ demonstrates a common factor for all symptoms, but also sub-groups of symptoms as previously suggested.

    Keyword
    Mild traumatic brain injury, post-concussion symptoms, rivermead post-concussion, symptoms, questionnaire
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-125599 (URN)10.1080/02699050902748356 (DOI)000263267100004 ()19205957 (PubMedID)
    Available from: 2010-05-24 Created: 2010-05-24 Last updated: 2017-12-12Bibliographically approved
    2. Internal construct validity of the Rivermead Post-Concussion Symptoms Questionnaire
    Open this publication in new window or tab >>Internal construct validity of the Rivermead Post-Concussion Symptoms Questionnaire
    Show others...
    2011 (English)In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 43, no 11, 997-1002 p.Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE: To investigate the internal construct validity of the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) by Rasch analysis of data from a national cohort of patients with mild traumatic brain injury.

    METHODS: Data collected at 3 months after mild traumatic brain injury from 2,523 patients were analysed using the partial credit model, describing rating scale structure, local dependency, age and gender differential functioning, dimensionality and model fit.

    RESULTS: Categories did not work in a consistent manner; however, collapsing of Categories 1 and 2 yielded ordered thresholds. Local dependency of items was present and 2 item pairs were combined. There was no differential item functioning by gender or age. The Rasch factor explained 47.7% of the variance and the first contrast explained 12.4% of the unexplained variance (eigenvalue 1.9). Further analysis indicated 3 or more dimensions. Person measure had a mean of -2.16, showing poor targeting of persons to items. Person reliability was 0.71 and person separation index was 1.56.

    CONCLUSION: According to this Rasch analysis of data from a representative sample of mild traumatic brain injury, the RPQ may not be optimal for this population. Even after reducing the number of categories and collapsing items with local dependency, unidimensionality was not reached, which argues against summation of a total score. However, the scale is unbiased for gender and age.

    National Category
    Other Clinical Medicine
    Research subject
    Rehabilitation Medicine
    Identifiers
    urn:nbn:se:uu:diva-161396 (URN)10.2340/16501977-0875 (DOI)000297658600006 ()22031345 (PubMedID)
    Available from: 2011-11-11 Created: 2011-11-11 Last updated: 2017-12-08Bibliographically approved
    3. Does head CT scan pathology predict outcome after mild traumatic brain injury?
    Open this publication in new window or tab >>Does head CT scan pathology predict outcome after mild traumatic brain injury?
    Show others...
    2013 (English)In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 20, no 1, 124-129 p.Article in journal (Refereed) Published
    Abstract [en]

    Background:

    More evidence is needed to forward our understanding of the key determinants of poor outcome after mild traumatic brain injury (MTBI). A large, prospective, national cohort of patients was studied to analyse the effect of head CT scan pathology on the outcome.

    Methods:

    Thousand two hundred and sixty-two patients with MTBI [Glasgow Coma Scale (GCS) score 15] at 39 emergency departments completed a study protocol including acute head CT scan examination and follow-up by the Rivermead Post Concussion Symptoms Questionnaire (RPQ) and the Glasgow Outcome Scale Extended (GOSE) at 3 months after MTBI. Binary logistic regression was used for the assessment of prediction ability.

    Results:

    In 751 men (60%) and 511 women (40%), with a mean age of 30 years (median 21, range 6–94), we observed relevant or suspect relevant pathologic findings on acute CT scan in 52 patients (4%). Patients aged below 30 years reported better outcome both with respect to symptoms and GOSE as compared to patients in older age groups. Men reported better outcome than women as regards symptoms (OR 0.64, CI 0.49–0.85 for 3 symptoms) and global function (OR 0.60, CI 0.39–0.92 for GOSE 1–6).

    Conclusions:

    Pathology on acute CT scan examination had no effect on selfreported symptoms or global function at 3 months after MTBI. Female gender and older age predicted a less favourable outcome. The findings support the view that other factors than brain injury deserve attention to minimize long-term complaints after MTBI.

    Keyword
    brain concussion, prediction
    National Category
    Other Clinical Medicine
    Research subject
    Rehabilitation Medicine
    Identifiers
    urn:nbn:se:uu:diva-180312 (URN)10.1111/j.1468-1331.2012.03813.x (DOI)000314996200019 ()
    Available from: 2012-09-03 Created: 2012-09-03 Last updated: 2017-12-07Bibliographically approved
    4. Clinical outcome and brain pathology after mild traumatic brain injury: an exploratory study by repeated MR examinations
    Open this publication in new window or tab >>Clinical outcome and brain pathology after mild traumatic brain injury: an exploratory study by repeated MR examinations
    (English)Manuscript (preprint) (Other academic)
    Keyword
    Brain concussion; Rivermead post-concussion symptoms questionnaire; Glasgow outcome scale extended
    National Category
    Other Clinical Medicine
    Research subject
    Rehabilitation Medicine
    Identifiers
    urn:nbn:se:uu:diva-180313 (URN)
    Available from: 2012-09-03 Created: 2012-09-03 Last updated: 2012-09-28
  • 35.
    Lannsjö, Marianne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Backheden, M
    Johansson, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    af Geijerstam, JL
    Borg, J
    Does head CT scan pathology predict outcome after mild traumatic brain injury?2013In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 20, no 1, 124-129 p.Article in journal (Refereed)
    Abstract [en]

    Background:

    More evidence is needed to forward our understanding of the key determinants of poor outcome after mild traumatic brain injury (MTBI). A large, prospective, national cohort of patients was studied to analyse the effect of head CT scan pathology on the outcome.

    Methods:

    Thousand two hundred and sixty-two patients with MTBI [Glasgow Coma Scale (GCS) score 15] at 39 emergency departments completed a study protocol including acute head CT scan examination and follow-up by the Rivermead Post Concussion Symptoms Questionnaire (RPQ) and the Glasgow Outcome Scale Extended (GOSE) at 3 months after MTBI. Binary logistic regression was used for the assessment of prediction ability.

    Results:

    In 751 men (60%) and 511 women (40%), with a mean age of 30 years (median 21, range 6–94), we observed relevant or suspect relevant pathologic findings on acute CT scan in 52 patients (4%). Patients aged below 30 years reported better outcome both with respect to symptoms and GOSE as compared to patients in older age groups. Men reported better outcome than women as regards symptoms (OR 0.64, CI 0.49–0.85 for 3 symptoms) and global function (OR 0.60, CI 0.39–0.92 for GOSE 1–6).

    Conclusions:

    Pathology on acute CT scan examination had no effect on selfreported symptoms or global function at 3 months after MTBI. Female gender and older age predicted a less favourable outcome. The findings support the view that other factors than brain injury deserve attention to minimize long-term complaints after MTBI.

  • 36.
    Lannsjö, Marianne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    Borg, Jörgen
    Björklund, Gunilla
    Af Geijerstam, Jean-Luc
    Lundgren-Nilsson, Asa
    Internal construct validity of the Rivermead Post-Concussion Symptoms Questionnaire2011In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 43, no 11, 997-1002 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the internal construct validity of the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) by Rasch analysis of data from a national cohort of patients with mild traumatic brain injury.

    METHODS: Data collected at 3 months after mild traumatic brain injury from 2,523 patients were analysed using the partial credit model, describing rating scale structure, local dependency, age and gender differential functioning, dimensionality and model fit.

    RESULTS: Categories did not work in a consistent manner; however, collapsing of Categories 1 and 2 yielded ordered thresholds. Local dependency of items was present and 2 item pairs were combined. There was no differential item functioning by gender or age. The Rasch factor explained 47.7% of the variance and the first contrast explained 12.4% of the unexplained variance (eigenvalue 1.9). Further analysis indicated 3 or more dimensions. Person measure had a mean of -2.16, showing poor targeting of persons to items. Person reliability was 0.71 and person separation index was 1.56.

    CONCLUSION: According to this Rasch analysis of data from a representative sample of mild traumatic brain injury, the RPQ may not be optimal for this population. Even after reducing the number of categories and collapsing items with local dependency, unidimensionality was not reached, which argues against summation of a total score. However, the scale is unbiased for gender and age.

  • 37.
    Liliegren, Julie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Persson, Frida
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Family-centered intervention: Auditory Verbal Therapy - empowering caregivers of children with cochlear implants2015Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The aims of this study were to examine a) whether the family-centered intervention method Auditory Verbal Therapy (AVT) has had an effect on the levels of empowerment of caregivers of children with CI; and b) whether the parents feeling most empowered have a continual habit of reading frequently with their child and have children who achieve higher scores on lexical-semantic tasks; c) whether the empowerment questionnaire “Att vara förälder” (“Being a parent”) is an appropriate assessment tool to evaluate intervention intending to empower the caregivers of children with hearing impairment. Vocabulary was used as a way to gauge the effectiveness of the method. Perceived empowerment of 23 parents was assessed with “Att vara förälder” (“Being a parent”) along with an informal conversation about the questionnaire. In addition, lexical-semantic ability of 11 children (age 5;1-11;8) was assessed with the BNT and the Semantic Feature Test for evaluation if the level of empowerment would affect vocabulary level. Overall the caregivers reported high levels of empowerment. Duration of intervention (range 6 months – 2 years or more) and levels of empowerment corresponded significantly positive. Further, a more active parent scored higher on empowerment than did the parent less active in intervention, as indicated by the self-reports. Qualitative data from the conversation revealed that many of the parents felt that the AVT intervention had helped them to feel more empowered. The results for lexical-semantic ability showed a large variability in the group, not significantly correlated to parents’ level of empowerment. The children older than eight years performed at stanine 5 and over on the BNT. The younger children did not score above stanine 4. In conclusion, the present study represents a first step towards applying empowerment as an instrument for the evaluation of family-centered intervention. Based on our results we argue that all children receiving a CI and their families would benefit from being provided with the possibility for prolonged intervention periods.

  • 38.
    Magnéli, Sara
    et al.
    Univ Uppsala Hosp, Dept Neurosurg, S-75185 Uppsala, Sweden.
    Howells, Timothy
    Univ Uppsala Hosp, Dept Neurosurg, S-75185 Uppsala, Sweden.
    Saiepour, Daniel
    Univ Uppsala Hosp, Dept Plast Surg, S-75185 Uppsala, Sweden.
    Nowinski, Daniel
    Univ Uppsala Hosp, Dept Plast Surg, S-75185 Uppsala, Sweden.
    Enblad, Per
    Univ Uppsala Hosp, Dept Neurosurg, S-75185 Uppsala, Sweden.
    Nilsson, Pelle
    Univ Uppsala Hosp, Dept Neurosurg, S-75185 Uppsala, Sweden.
    Telemetric intracranial pressure monitoring: a noninvasive method to follow up children with complex craniosynostoses. A case report2016In: Child's nervous system (Print), ISSN 0256-7040, E-ISSN 1433-0350, Vol. 32, no 7, 1311-1315 p.Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: There are no reliable noninvasive methods of monitoring ICP. Most assessments are made by indirect measures and are difficult to follow over time. Invasive studies can be used but up until now have required in-hospital transcutaneous measurements. Accurate ICP recordings over longer periods of time can be very valuable in timing different surgical procedures in syndromal cases. This case shows that telemetric ICP monitoring can be used for long-term follow-up in patients that may need repeated surgeries related to their craniosynostosis condition.

    CASE REPORT: In this report, the telemetric ICP probe (Raumedic Neurovent-P-tel) was implanted before surgery and was used for repeated "noninvasive" ICP recordings pre- and postoperatively in a patient with craniosynostosis. The patient was an eight-year-old girl with pansynostosis with only the right lambdoid suture open. A telemetric ICP probe was implanted the day before cranial vault remodeling and the ICP was monitored pre- and postoperatively. The ICP was above 15 mmHg 72.2 % of the monitoring time before surgery, and the amplitude of the curve was greater than normal suggesting impaired compliance. Direct postoperative ICP was normal, and the amplitude was lower. The ICP was then monitored both in out-patient clinic and in four longer hospital stays. Both the values and the curves were analyzed, and the time with ICP above 15 mmHg decreased over time, and the waveform amplitude of the curves improved.

    CONCLUSION: This "noninvasive" way of recording ICP is a feasible and helpful tool in decision-making and intervening in patients with craniosynostosis.

  • 39.
    Mannervik, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Runarsdottir, Arna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Kurtovic, Sanela
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Multi-substrate-activity space and quasi-species in enzyme evolution: Ohno's dilemma, promiscuity and functional orthogonality2009In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 37, no Pt 4, 740-744 p.Article in journal (Refereed)
    Abstract [en]

    A functional enzyme displays activity with at least one substrate and can be represented by a vector in substrate-activity space. Many enzymes, including GSTs (glutathione transferases), are promiscuous in the sense that they act on alternative substrates, and the corresponding vectors operate in multidimensional space. The direction of the vector is governed by the relative activities of the diverse substrates. Stochastic mutations of already existing enzymes generate populations of variants, and clusters of functionally similar mutants can serve as parents for subsequent generations of enzymes. The proper evolving unit is a functional quasi-species, which may not be identical with the 'best' variant in its generation. The manifestation of the quasi-species is dependent on the substrate matrix used to explore catalytic activities. Multivariate analysis is an approach to identifying quasi-species and to investigate evolutionary trajectories in the directed evolution of enzymes for novel functions.

  • 40.
    Marrero, Humberto Gonzalez
    et al.
    Karolinska Inst, Dept Clin Neurosci, Clin Neurophysiol Sect, Stockholm, Sweden.
    Stålberg, Erik V
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Optimizing testing methods and collection of reference data for differentiating critical illness polyneuropathy from critical illness myopathy.2016In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 53, no 4, 555-563 p.Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: In severe acute quadriplegic myopathy in intensive care unit (ICU) patients, muscle fibers are electrically inexcitable; in critical illness polyneuropathy the excitability remains normal. Conventional electrodiagnostic methods do not provide the means to adequately differentiate between them.

    OBJECTIVE: To further optimize methodology for the study of critically ill ICU patients and to create a reference database in healthy controls.

    METHODS: Different electrophysiologic protocols were tested to find sufficiently robust and reproducible techniques for clinical diagnostic applications.

    RESULTS: Many parameters show large test-retest variability within the same healthy subject. Reference values have been collected and described as a basis for studies of weakness in critical illness.

    DISCUSSION: Using the ratio of neCMAP/dmCMAP (response from nerve and direct muscle stimulation), refractory period, and stimulus-response curves may optimize the electrodiagnostic differentiation of patients with critical illness myopathy from those with critical illness polyneuropathy.

  • 41.
    Michaëlsson, Karl
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Warensjö Lemming, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wolk, Alicja
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Long term calcium intake and rates of all cause and cardiovascular mortality: community based prospective longitudinal cohort study2013In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 346, f228Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To investigate the association between long term intake of dietary and supplemental calcium and death from all causes and cardiovascular disease.

    DESIGN:

    Prospective longitudinal cohort study.

    SETTING:

    Swedish mammography cohort, a population based cohort established in 1987-90.

    PARTICIPANTS:

    61 433 women (born between 1914 and 1948) followed-up for a median of 19 years.

    MAIN OUTCOME MEASURES:

    Primary outcome measures, identified from registry data, were time to death from all causes (n=11 944) and cause specific cardiovascular disease (n=3862), ischaemic heart disease (n=1932), and stroke (n=1100). Diet was assessed by food frequency questionnaires at baseline and in 1997 for 38 984 women, and intakes of calcium were estimated. Total calcium intake was the sum of dietary and supplemental calcium.

    RESULTS:

    The risk patterns with dietary calcium intake were non-linear, with higher rates concentrated around the highest intakes (≥1400 mg/day). Compared with intakes between 600 and 1000 mg/day, intakes above 1400 mg/day were associated with higher death rates from all causes (hazard ratio 1.40, 95% confidence interval 1.17 to 1.67), cardiovascular disease (1 49, 1.09 to 2.02), and ischaemic heart disease (2.14, 1.48 to 3.09) but not from stroke (0.73, 0.33 to 1.65). After sensitivity analysis including marginal structural models, the higher death rate with low dietary calcium intake (<600 mg/day) or with low and high total calcium intake was no longer apparent. Use of calcium tablets (6% users; 500 mg calcium per tablet) was not on average associated with all cause or cause specific mortality but among calcium tablet users with a dietary calcium intake above 1400 mg/day the hazard ratio for all cause mortality was 2.57 (95% confidence interval 1.19 to 5.55).

    CONCLUSION:

    High intakes of calcium in women are associated with higher death rates from all causes and cardiovascular disease but not from stroke.

  • 42.
    Mindemark, Mirja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    The Use of Laboratory Analyses in Sweden: Quality and Cost-Effectiveness in Test Utilization2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Laboratory analyses, essential in screening, diagnosis, treatment, and monitoring of disease, are indispensable in health care, but appropriate utilization is intricate. The overall aim of this thesis was to study the use of laboratory tests in Sweden with the objective to evaluate and optimize test utilization.

    Considerable inter-county variations in test utilization in primary health care in Sweden were found; variations likely influenced by local traditions and habits of test ordering leading to over- as well as underutilization. Optimized test utilization was demonstrated to convey improved quality and substantial cost savings.

    It was further established that continuing medical education is a suitable means of optimizing test utilization, and consequently enhancing quality and cost-efficiency, as such education was demonstrated to achieve long-lasting improvements in the test ordering habits of primary health care physicians.

    Laboratory tests are closely associated with other, greater, health care costs, but their indirect effects on other areas of medicine are rarely evaluated or measured in monetary terms. In an illustrative example of the effects that optimal test utilization may have on associated health care costs it was demonstrated that F-calprotectin, a fecal marker of intestinal inflammation, has the potential to substantially reduce the number of invasive investigations necessary in, and the costs associated with, the diagnosis of Inflammatory Bowel Disease.

    Information on trends in test utilization is essential to optimal financial management of laboratories. A longitudinal evaluation revealed that test utilization had increased by 70% in 6 years, and even though the selection of tests more than doubled, a very small number of tests represented a stable, and disproportionally large, share of the total number of tests ordered. The study defines trends and thus has potential predictive values.

    In summary, appropriate utilization of laboratory analyses has both clinical and economical benefits on all levels of health care.

    List of papers
    1. Long-term effects of an education programme on the optimal use of clinical chemistry testing in primary health care
    Open this publication in new window or tab >>Long-term effects of an education programme on the optimal use of clinical chemistry testing in primary health care
    2009 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 69, no 4, 481-486 p.Article in journal (Refereed) Published
    Abstract [en]

    Objective: The aim of this study was to investigate whether continuing education on the optimal use of clinical chemistry testing in primary health care has had any long‐term effects on the test‐ordering behaviour of the participating physicians. Methods: The effects were monitored using 12 laboratory test ratios. Twenty‐three general practitioners at 16 primary health‐care centres in the county of Uppsala, Sweden, participated. A sign test was used to evaluate how individual physicians' test‐ordering patterns have changed during the 8 years since implementation of the educational programme. Maintained or improved ratios were interpreted as a sustained effect on the primary health‐care physician's test‐ordering habits. Results: Eleven out of 12 of the investigated ratios were the same or improved since the time of the short‐term follow‐up 6 months after the education. Conclusion: A short continuation course on optimal use of clinical chemistry assays can achieve permanent changes in the test‐ordering patterns of primary health‐care physicians. These findings highlight education as one possible means towards achieving cost‐efficiency and quality in test‐ordering.

    Keyword
    continuing medical education, cost control, cost savings, organizational efficiency, physician practice patterns, routine diagnostic tests
    National Category
    Other Clinical Medicine
    Research subject
    Biomedical Laboratory Science
    Identifiers
    urn:nbn:se:uu:diva-119610 (URN)10.1080/00365510902749123 (DOI)000267287000007 ()19340700 (PubMedID)
    Available from: 2010-02-26 Created: 2010-02-26 Last updated: 2017-12-12Bibliographically approved
    2. Ruling out IBD: Estimation of the possible economic effects of pre-endoscopic screening with F-calprotectin
    Open this publication in new window or tab >>Ruling out IBD: Estimation of the possible economic effects of pre-endoscopic screening with F-calprotectin
    2012 (English)In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 45, no 7-8, 552-555 p.Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: To estimate the possible economic effects of a sequential testing strategy with F-calprotectin to minimize colonoscopies.

    DESIGN AND METHODS: Retrospective study in a third party payer perspective. The costs were calculated from initial F-calprotectin test results of 3639 patients. Two cut-off levels were used: 50μg/g feces and 100μg/g feces, respectively. The cost-effectiveness of the testing strategy was estimated through the short-term cost avoidance and reduction in demand for colonoscopies.

    RESULTS: The estimated demand for colonoscopies was reduced by 50% with the 50μg/g cut-off and 67% with the 100μg/g cut-off. This corresponded to a cost avoidance of approximately €1.57million and €2.13million, respectively.

    CONCLUSIONS: The use of F-calprotectin as a screening test substantially could reduce the number of invasive measurements necessary in the diagnostic work-up of patients with suspected IBD, as well as the associated costs.

    Keyword
    cost-effectiveness, diagnostic tests, health care costs, inflammatory bowel disease, irritable bowel syndrome, calprotectin
    National Category
    Other Clinical Medicine
    Research subject
    Biomedical Laboratory Science
    Identifiers
    urn:nbn:se:uu:diva-120552 (URN)10.1016/j.clinbiochem.2011.10.015 (DOI)000303553300008 ()
    Note
    Original title of the manuscript: Ruling out IBD: The cost-effectiveness of pre-endoscopic screening with F-calprotectinAvailable from: 2010-03-12 Created: 2010-03-12 Last updated: 2017-12-12Bibliographically approved
    3. Longitudinal trends in laboratory test utilization at a large tertiary care university hospital in Sweden
    Open this publication in new window or tab >>Longitudinal trends in laboratory test utilization at a large tertiary care university hospital in Sweden
    2011 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 116, no 1, 34-38 p.Article in journal (Refereed) Published
    Abstract [en]

    Background. The aim of the study was to describe and evaluate longitudinal trends in laboratory test utilization over a 7-year period from 2002 to 2008. Method. Retrospective study using test request data from the Clinical Chemistry and Pharmacology Laboratory at Akademiska Sjukhuset, a large tertiary care university hospital in Sweden. Changes in test utilization, charges, and expenditures during the study period were used as main outcome measures. Results. Laboratory test utilization increased by over 70%, with a mean annual increase of 9.3% during the study period. After adjustment for inflation, the laboratory expenditures increased by 20.2% during the study period but represented only approximately 2.0% of the hospital's total expenditure in 2008. The test menu comprised 663 tests in 2008, an increase by 146% from 2002. The mean inflation-adjusted unit price charged per test increased from €34.9 to €37.5 during the study period. The top 10, 20, and 30 tests accounted for, on average, 46.9%, 66.9%, and 75.5% of the total test volume during the study period, and 47.8%, 66.4%, and 75.7% of the total test volume in 2008. In 2008, 10 analyses, i.e. 1.5% of the number of tests on the menu, accounted for almost half the number of generated test results. Conclusions. The total number of generated test results increased by over 70% in less than a decade. Even so, the laboratory's share of the hospital's total expenditure remained low and virtually unchanged. A very small number of tests accounted for a disproportionately large share of the total number of generated test results.

     

    Keyword
    clinical laboratory techniques, clinical chemistry, economics of laboratory operation, health care costs, laboratory management, test utilization, trends
    National Category
    Other Clinical Medicine
    Research subject
    Biomedical Laboratory Science
    Identifiers
    urn:nbn:se:uu:diva-120553 (URN)10.3109/03009734.2010.528071 (DOI)000287312100005 ()21067458 (PubMedID)
    Available from: 2010-03-12 Created: 2010-03-12 Last updated: 2017-12-12Bibliographically approved
    4. Costly regional variations in primary health care test utilization in Sweden
    Open this publication in new window or tab >>Costly regional variations in primary health care test utilization in Sweden
    2010 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 70, no 3, 164-170 p.Article in journal (Refereed) Published
    Abstract [en]

    Objective: Laboratory tests are used increasingly in primary health care and they are thus associated with rapidly growing costs. Variations in clinical practice, an important determinant of expenditure for laboratory tests, could further increase the financial burden. The study's threefold objective was to determine the presence and extent of regional variations in test ordering between eight counties in Sweden, to investigate the influence on these variations by factors earlier described in the literature as explanatory, and to calculate the achievable savings that could be realized through optimized test ordering. Design: A retrospective study using test request data. Setting: A total of 223 primary health care centers in eight counties in Sweden. Main outcome measures: Thirteen ratios of commonly used laboratory tests, demographic data and the number of ordered tests per 1000 inhabitants served as the basis of comparison. The total savings per 100,000 inhabitants that could be achieved through optimized test ordering was estimated. Results: Large variations were found between all studied counties for all investigated ratios. However, none of the demographic variables investigated seemed to be able to explain the full extent of the variations. The range of achievable yearly savings per 100,000 inhabitants was euro14,000-euro185,000. Conclusion: The inter-county variations in Sweden are large and the savings associated with optimized test utilization are substantial. The investigated factors previously described as explaining the variations in test ordering only seem to explain a small part of the variation, and the variations are likely influenced by regional habits and traditions.

    Keyword
    clinical chemistry tests, cost savings, diagnostic tests, family practice, health care costs, physicians' practice patterns
    National Category
    Medical and Health Sciences
    Research subject
    Biomedical Laboratory Science
    Identifiers
    urn:nbn:se:uu:diva-120551 (URN)10.3109/00365511003642519 (DOI)000276814500004 ()20178451 (PubMedID)
    Available from: 2010-03-12 Created: 2010-03-12 Last updated: 2017-12-12Bibliographically approved
  • 43.
    Mindemark, Mirja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Longitudinal trends in laboratory test utilization at a large tertiary care university hospital in Sweden2011In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 116, no 1, 34-38 p.Article in journal (Refereed)
    Abstract [en]

    Background. The aim of the study was to describe and evaluate longitudinal trends in laboratory test utilization over a 7-year period from 2002 to 2008. Method. Retrospective study using test request data from the Clinical Chemistry and Pharmacology Laboratory at Akademiska Sjukhuset, a large tertiary care university hospital in Sweden. Changes in test utilization, charges, and expenditures during the study period were used as main outcome measures. Results. Laboratory test utilization increased by over 70%, with a mean annual increase of 9.3% during the study period. After adjustment for inflation, the laboratory expenditures increased by 20.2% during the study period but represented only approximately 2.0% of the hospital's total expenditure in 2008. The test menu comprised 663 tests in 2008, an increase by 146% from 2002. The mean inflation-adjusted unit price charged per test increased from €34.9 to €37.5 during the study period. The top 10, 20, and 30 tests accounted for, on average, 46.9%, 66.9%, and 75.5% of the total test volume during the study period, and 47.8%, 66.4%, and 75.7% of the total test volume in 2008. In 2008, 10 analyses, i.e. 1.5% of the number of tests on the menu, accounted for almost half the number of generated test results. Conclusions. The total number of generated test results increased by over 70% in less than a decade. Even so, the laboratory's share of the hospital's total expenditure remained low and virtually unchanged. A very small number of tests accounted for a disproportionately large share of the total number of generated test results.

     

  • 44.
    Mindemark, Mirja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Long-term effects of an education programme on the optimal use of clinical chemistry testing in primary health care2009In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 69, no 4, 481-486 p.Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to investigate whether continuing education on the optimal use of clinical chemistry testing in primary health care has had any long‐term effects on the test‐ordering behaviour of the participating physicians. Methods: The effects were monitored using 12 laboratory test ratios. Twenty‐three general practitioners at 16 primary health‐care centres in the county of Uppsala, Sweden, participated. A sign test was used to evaluate how individual physicians' test‐ordering patterns have changed during the 8 years since implementation of the educational programme. Maintained or improved ratios were interpreted as a sustained effect on the primary health‐care physician's test‐ordering habits. Results: Eleven out of 12 of the investigated ratios were the same or improved since the time of the short‐term follow‐up 6 months after the education. Conclusion: A short continuation course on optimal use of clinical chemistry assays can achieve permanent changes in the test‐ordering patterns of primary health‐care physicians. These findings highlight education as one possible means towards achieving cost‐efficiency and quality in test‐ordering.

  • 45.
    Mindemark, Mirja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ruling out IBD: Estimation of the possible economic effects of pre-endoscopic screening with F-calprotectin2012In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 45, no 7-8, 552-555 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To estimate the possible economic effects of a sequential testing strategy with F-calprotectin to minimize colonoscopies.

    DESIGN AND METHODS: Retrospective study in a third party payer perspective. The costs were calculated from initial F-calprotectin test results of 3639 patients. Two cut-off levels were used: 50μg/g feces and 100μg/g feces, respectively. The cost-effectiveness of the testing strategy was estimated through the short-term cost avoidance and reduction in demand for colonoscopies.

    RESULTS: The estimated demand for colonoscopies was reduced by 50% with the 50μg/g cut-off and 67% with the 100μg/g cut-off. This corresponded to a cost avoidance of approximately €1.57million and €2.13million, respectively.

    CONCLUSIONS: The use of F-calprotectin as a screening test substantially could reduce the number of invasive measurements necessary in the diagnostic work-up of patients with suspected IBD, as well as the associated costs.

  • 46.
    Mitander, Maria
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Evaluation of platelet parameters from Advia 2120 and Sysmex XT-2000iV in samples from dogs, horses and cats.2008Independent thesis Basic level (degree of Bachelor), 15 credits / 22,5 HE creditsStudent thesis
    Abstract [en]

    Haematology instruments using optical and fluorescence techniques have improved the platelet count in domestic animals. There are still some difficulties present, especially when counting cat thrombocytes due to their ability to aggregate and the occurrence of large platelets.

    The objective of this study was to evaluate and compare the platelet count, mean platelet volume and platelet crit in dogs, horses and cats on Advia 2120 and Sysmex XT-2000iV.

    Fresh blood samples from 64 dogs, 40 horses and 39 cats with various medical conditions were analysed on both instruments. Manual blood smears of all feline samples were scrutiniously analysed to evaluate the aggregation warning flag from Advia.

    There was good agreement between the instruments for the optical platelet count in dogs and cats. Slightly higher values were reported from Advia. Samples from horses presented poor correlations for all studied parameters. Platelet clumps appeared in 70% of the 37 scrutinized feline blood smears, while 46% of the samples generated aggregation warning flags from the Advia instrument.

    Advia and Sysmex showed good agreement for platelet counts in blood from dogs and cats. Mean platelet volume and platelet crit need further evaluation before conclusions can be made concerning their clinical relevance. The sensitivity of the platelet aggregation warning flag from the Advia instument needs further elevation.

  • 47.
    Moens, Lotte. N.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Falk-Sörqvist, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    La Fleur, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Mattsson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Bergfors, M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sundström, M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Nilsson, M.
    Stockholm Univ, S-10691 Stockholm, Sweden..
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Clinical Validation of HaloPlex Targeted Resequencing in Formalin-Fixed, Paraffin-Embedded (FFPE) Cancer Biopsies2015In: Journal of Molecular Diagnostics, ISSN 1525-1578, E-ISSN 1943-7811, Vol. 17, no 6, 822-822 p.Article in journal (Other academic)
  • 48.
    Nilsson, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Characterization of IgY for Oral Immunotherapy and Prevention of Pseudomonas aeruginosa Infections in Cystic Fibrosis Patients2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Chicken antibodies, commonly referred to as IgY, have several properties that make them suitable for oral treatment of infections and there is essentially no risk for development of resistance. The overall aims of this thesis were to investigate Anti-Pseudomonas IgY as prophylaxis against infections with Pseudomonas aeruginosa for cystic fibrosis (CF) patients and to characterize the antibody treatment.

    We found that Anti-Pseudomonas IgY has affinity for P. aeruginosa flagellin, the major component of the flagellum. This is important since the flagellum is required for host invasion and establishment of infection. Flagellin induces inflammation.

    The main cause of morbidity and mortality among CF patients is chronic colonization of the airways with P. aeruginosa. We have studied prophylactic treatment of 17 Swedish CF patients with Anti-Pseudomonas IgY for up to twelve years. The results were compared with a control group of 23 Danish CF patients. Patients treated with IgY had 2.3 P. aeruginosa positive cultures/100 treatment months vs. 7.0 cultures/100 treatment months in the control group (p=0.028), and the time from inclusion to the first recolonization was significantly longer in the IgY-treated group (p=0.012). Lung function was preserved and patients treated with IgY had good nutritional status at the end of the study. Furthermore, other bacteria have not emerged instead of P. aeruginosa.

    Freeze-drying of IgY and the content of IgY preparations for oral use was investigated. Besides IgY, 26 egg yolk proteins were identified. Some of the proteins are known to have antimicrobial and immunostimulatory effects, and could have a positive additive effect to IgY treatment. Cholesterol levels were low.

    Conclusion: Anti-Pseudomonas IgY is a promising complement in the prevention of Pseudomonas aeruginosa infections in CF patients, partly explained by the fact that IgY binds to flagellin.

    List of papers
    1. Stability of chicken IgY antibodies freeze-dried in the presence of lactose, sucrose and trehalose
    Open this publication in new window or tab >>Stability of chicken IgY antibodies freeze-dried in the presence of lactose, sucrose and trehalose
    2007 (English)In: Journal of Poultry Science, ISSN 1349-0486, Vol. 44, no 1, 58-62 p.Article in journal (Refereed) Published
    Abstract [en]

    Freeze-drying is used as a method to stabilize proteins. The process itself may however cause protein unfolding and denaturation, but the risk is reduced if a stabilizing agent is added prior to freeze-drying. Here chicken antibody (IgY) preparations were freeze-dried in the presence or absence of lactose, sucrose and threalose as stabilizing agent at 0.3, 0.06 and 0.012M. The activity of freeze-dried IgY batches in the absence of stabilizing agent was similar before and after freeze-drying, but decreased slowly during eight weeks at 37°C. Addition of disaccharide resulted in a preserved activity after eight weeks in 37°C, compared to samples with no sugar added. The results were similar irrespective of sugar type and concentration (0.012-0.3M). This shows that IgY freeze-dried in the presence of disaccharide is very stable and a method to reduce the cost and simplify transport, storage and use of avian antibodies.

    Keyword
    ELISA, freeze-drying, IgY, lactose, sucrose, threalose
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-12980 (URN)
    Available from: 2008-01-19 Created: 2008-01-19 Last updated: 2010-04-09Bibliographically approved
    2.
    The record could not be found. The reason may be that the record is no longer available or you may have typed in a wrong id in the address field.
    3. Pseudomonas aeruginosa infections are prevented in cystic fibrosis patients by avian antibodies binding Pseudomonas aeruginosa flagellin: Pseudomonas aeruginosa infections are prevented in cystic fibrosis patients by avian antibodies binding Pseudomonas aeruginosa flagellin
    Open this publication in new window or tab >>Pseudomonas aeruginosa infections are prevented in cystic fibrosis patients by avian antibodies binding Pseudomonas aeruginosa flagellin: Pseudomonas aeruginosa infections are prevented in cystic fibrosis patients by avian antibodies binding Pseudomonas aeruginosa flagellin
    2007 (English)In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 856, no 1-2, 75-80 p.Article in journal (Refereed) Published
    Abstract [en]

    Pseudomonas aeruginosa (PA) is the main cause of morbidity and mortality in cystic fibrosis (CF) patients. CF patients with chronic PA infections have a more rapid deterioration of their lung function and the bacteria become impossible to eradicate from the lungs. Antibiotic resistance among PA strains in CF patients is steadily increasing. Specific chicken (IgY) antibodies against PA have been shown to have potential to prevent PA infections in CF. Anti-Pseudomonas IgY reduces PA adhesion to epithelia, but the mechanism has not been fully elucidated. To gain further insight into the prophylactic effect of these antibodies, the immunoreactivity was investigated by 2D electrophoresis of PA strains, immunoblotting and MALDI-TOF-MS. To confirm the identity of the proteins, the tryptic peptides were analyzed by MALDI-TOF-MS to accurately measure their monoisotopic masses as well as determine their amino acid sequences. In order to facilitate fragmentation of the peptides they were N-terminally or C-terminally labeled. Several strains were investigated and anti-Pseudomonas IgY was immunoreactive against all of these strains, which strengthens its potential as a prophylactic treatment against PA. Flagellin was identified as the major antigen. Flagellin is the main protein of the flagella and is crucial for establishing infections in hosts as well as being involved in PA chemotaxis, motility, adhesion and inflammation. Furthermore, secreted flagellin elicits an inflammatory response. In conclusion, anti-Pseudomonas IgY binds flagellin, which may prevent PA infections in CF patients by hindering host invasion.

    Keyword
    two-dimensional gel electrophoresis, antigen, IgY, mass spectrometry, proteomics
    National Category
    Medical and Health Sciences Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-100189 (URN)10.1016/j.jchromb.2007.05.029 (DOI)000249615100012 ()17581799 (PubMedID)
    Available from: 2009-03-26 Created: 2009-03-26 Last updated: 2017-12-13Bibliographically approved
    4.
    The record could not be found. The reason may be that the record is no longer available or you may have typed in a wrong id in the address field.
  • 49.
    Penell, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lundmark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Morris, Andrew P
    Lindgren, Cecilia
    Mahajan, Anubha
    Salihovic, Samira
    van Bavel, Bert
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, P Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Genetic variation in the CYP2B6 Gene is related to circulating 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) concentrations: an observational population-based study2014In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 13, 34- p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Since human CYP2B6 has been identified as the major CYP enzyme involved in the metabolism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and that human 2B6 is a highly polymorphic CYP, with known functional variants, we evaluated if circulating concentrations of a major brominated flame retardant, BDE-47, were related to genetic variation in the CYP2B6 gene in a population sample.

    METHODS:

    In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (men and women all aged 70), 25 single nucleotide polymorphisms (SNPs) in the CYP2B6 gene were genotyped. Circulating concentrations of BDE-47 were analyzed by high-resolution gas chromatography coupled to high-resolution mass spectrometry (HRGC/ HRMS).

    RESULTS:

    Several SNPs in the CYP2B6 gene were associated with circulating concentrations of BDE-47 (P = 10-4 to 10-9). The investigated SNPs came primarily from two haplotypes, although the correlation between the haplotypes was rather high. Conditional analyses adjusting for the SNP with the strongest association with the exposure (rs2014141) did not provide evidence for independent signals.

    CONCLUSION:

    Circulating concentrations of BDE-47 were related to genetic variation in the CYP2B6 gene in an elderly population.

  • 50.
    Peng, Z.
    et al.
    Karolinska Inst, Stockholm, Sweden..
    Andersson, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lindholm, J.
    Karolinska Univ Hosp, Stockholm, Sweden..
    Hrydziuszko, O.
    Karolinska Inst, Stockholm, Sweden..
    Pramana, S.
    Karolinska Inst, Stockholm, Sweden..
    Pawitan, Y.
    Karolinska Inst, Stockholm, Sweden..
    Nister, M.
    Karolinska Inst, Stockholm, Sweden..
    Nilsson, S.
    Karolinska Inst, Stockholm, Sweden..
    Li, C.
    Karolinska Inst, Stockholm, Sweden..
    Improving the Prediction of Prostate Cancer Overall Survival by Supplementing Readily Available Clinical Data with Gene Expression Levels of IGFBP3 and F3 in Formalin-Fixed, Paraffin-Embedded Core Needle Biopsy Material2015In: Journal of Molecular Diagnostics, ISSN 1525-1578, E-ISSN 1943-7811, Vol. 17, no 6, 815-815 p.Article in journal (Other academic)
12 1 - 50 of 66
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