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  • 1. Andersen, Toril
    et al.
    Vanić, Zeljka
    Flaten, Gøril Eide
    Mattsson, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Tho, Ingunn
    Skalko-Basnet, Nataša
    Pectosomes and chitosomes as delivery systems for metronidazole: the one-pot preparation method2013Inngår i: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 5, nr 3, 445-456 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mucoadhesive liposomes offer a potential for improved residence time of liposomal systems targeting contact with mucosal tissues, such as in buccal, oral, colon, and vaginal drug delivery. Most of the currently available methods rely on the coating of preformed liposomes by various mucoadhesive polymers. The aim of this study was to develop novel mucoadhesive system by the one-pot preparation method. The pectin- and chitosan-containing liposomes, namely pectosomes and chitosomes, were prepared by the modified solvent injection method. In order to optimize this novel delivery system, we used pectins and chitosans of both high and low degree of esterification/deacetylation (DE/DD), respectively. Sonication was applied to reduce the original vesicle size. All vesicles were characterized for their size, zeta potential, metronidazole entrapment, and stability. Both pectosomes and chitosomes were found to entrap more metronidazole than conventional plain liposomes. Preliminary data indicate that the polymer is present on the liposomal surface, embedded within inner liposomal bilayers, and entrapped inside the aqueous compartment. The next step in the evaluation of this system is the testing of its mucoadhesiveness.

  • 2. Benetou, V
    et al.
    Orfanos, P
    Zylis, D
    Sieri, S
    Contiero, P
    Tumino, R
    Giurdanella, M C
    Peeters, P H M
    Linseisen, J
    Nieters, A
    Boeing, H
    Weikert, C
    Pettersson, U
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Kariologi.
    Bueno-de-Mesquita, H B
    Dorronsoro, M
    Boffetta, P
    Trichopoulou, A
    Diet and hip fractures among elderly Europeans in the EPIC cohort2011Inngår i: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 65, nr 1, 132-139 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In a prospective study of the elderly, diet, including consumption of dairy products, alcohol and vitamin D, did not appear to play a major role in hip fracture incidence. There is however, weak and statistically non-significant evidence that vegetable and fish consumption and intake of polyunsaturated lipids may have a beneficial, whereas saturated lipid intake a detrimental effect.

  • 3. Benetou, Vassiliki
    et al.
    Orfanos, Philippos
    Benetos, Ioannis S
    Pala, Valeria
    Evangelista, Alberto
    Frasca, Graziella
    Giurdanella, Maria Concetta
    Peeters, Petra HM
    van der Schouw, Yvonne T
    Rohrmann, Sabine
    Linseisen, Jakob
    Boeing, Heiner
    Weikert, Cornelia
    Pettersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bueno-de-Mesquita, H Bas
    Altzibar, Jone
    Boffetta, Paolo
    Trichopoulou, Antonia
    Anthropometry, physical activity and hip fractures in the elderly2011Inngår i: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 42, nr 2, 188-193 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: Hip fractures constitute a major and growing public health problem amongst the elderly worldwide. We examined the association of anthropometry and physical activity with hip fracture incidence in a cohort of elderly Europeans, participants in the European Prospective Investigation into Cancer and nutrition (EPIC) study.

    MATERIALS AND METHODS: The study population consisted of 27982 volunteers (10553 men and 17429 women) aged 60 years and above from five European countries. Information on anthropometry, physical activity, medical history and other characteristics was collected at baseline. During a median follow-up of 8 years, 261 incident hip fractures (203 women and 58 men) were recorded. Data were analysed through Cox proportional hazard regression with adjustment for potential confounders.

    RESULTS: A higher body mass index (BMI) was associated with lower hip fracture risk (hazard ratio (HR) per increasing sex-specific-quintile: 0.85, 95% confidence interval (95% CI): 0.77-0.94). Body height was associated with increased hip fracture risk (HR per 5cm: 1.13, 95% CI: 1.01-1.25). Waist-to-hip ratio was not related to hip fracture risk. Increasing levels of leisure-time physical activity were related to lower risk (HR per increasing tertile: 0.84, 95% CI: 0.70-0.99, p for trend: 0.039).

    CONCLUSIONS: In a prospective cohort study of elderly Europeans, we found evidence that high body stature increased and high BMI decreased the incidence of hip fractures. After adjustment for BMI, waist-to-hip ratio was not associated with hip fracture risk. Leisure-time physical activity appears to play a beneficial role in the prevention of hip fractures.

  • 4. Bergström, Erik
    et al.
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Dahlqvist, Rune
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Birgander, Lisbeth Slunga
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    [Do better next time]2009Inngår i: Läkartidningen, ISSN 0023-7205, Vol. 106, nr 8, 527- s.Artikkel i tidsskrift (Annet vitenskapelig)
  • 5.
    Bergström, Ulrica
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Pettersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    The hip fracture incidence curve is shifting to the right: a forecast of the age-quake2009Inngår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 80, nr 5, 520-524 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The number of hip fractures has doubled in the last 30–40 years in many countries. Age-adjusted incidence has been reported to be decreasing in Europe and North America, but is there a decreasing trend in all age groups? Patients and methods This population-based study included all hip-fracture patients over 50 years of age (a total of 2,919 individuals, 31% of whom were men) admitted to Umeå University Hospital, Sweden, from 1993 through 2005. Results The incidence of hip fracture declined between the periods 1993–1996 and 2001–2005: from 706 to 625 hip fractures per 105 women and from 390 to 317 hip fractures per 105 men. However, there was a 114% increase in the number of fractures in women aged 90 or older (12 and 25 hip fractures/year, respectively, in the two time periods). For the period 2001–05, women ≥ 90 years of age accounted for almost the same numbers of hip fractures as women aged 75–79 (27 fractures/year). The rate increased during this period, from 2,700 per 105 women to 3,900 per 105 women > 90 years. In men there were declining trends for both relative and absolute numbers. Interpretation Although age-adjusted incidence declined in the population > 50 years of age, absolute fracture rate and incidence increased in the very old. Women over 90 now have the same absolute number of hip fractures every year as women aged 75–79 years. There was a right-shift in hip fracture distribution towards the oldest old, probably due to an increased number of octo/nonagenarians, a new population of particularly frail old people that hardly existed earlier. Better health among septuagenarians may also have delayed the age at which fractures occurred. This changing pattern will strain orthopedic and geriatric resources even more.

  • 6. Boman, Jens
    et al.
    Schneede, Jörn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Nylander, Elisabet
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Dermatologi och venereologi.
    Genitala klamydiainfektioner: rekommenderad handläggning2011Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, nr 13, 730-733 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    Klamydia är den vanligaste anmälningspliktiga infektionen i Sverige: 37 791 fall rapporterades till Smittskyddsinstitutet år 2009, och 87 procent av de smittade var i åldern 15–29 år.

    Klamydiainfektion är klassad som allmänfarlig sjukdom enligt smittskyddslagen, vilket bl a innebär att en läkare som misstänker att en patient bär på smitta är skyldig att se till att patienten lämnar prov, och vid positivt provresultat se till att förhållningsregler ges samt att smittskyddsanmälan och smittspårning görs.

    Provtagning görs vanligen med urinprov hos män och med självtaget vaginalprov hos kvinnor, eventuellt kombinerat med urinprov.

    Majoriteten av personer med klamydia har subkliniska infektioner men kan ändå få bestående reproduktiva skador och föra smittan vidare. Ungefär var tionde kvinna med obehandlad klamydiainfektion utvecklar klinisk salpingit inom en tolvmånadersperiod. Klamydiaorsakad salpingit ökar risken för utomkvedshavandeskap och nedsatt fertilitet.

    Okomplicerad genital klamydiainfektion behandlas i Sverige med doxycyklin, vanligen i lägre dosering än i många andra länder. Det är därför viktigt att se till att hela kuren tas enligt anvisningarna och att patienten informeras om att samtidigt intag av vissa läkemedel, spårämnen och födoämnen liksom alkohol kan resultera i suboptimal antibiotikaeffekt.

  • 7.
    Bredenberg, Susanne
    et al.
    Orexo AB, SE-75105 Uppsala, Sweden.
    Dahlgren, Anna
    Orexo AB, SE-75105 Uppsala, Sweden.
    Mattsson, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Evaluation of a sieve classification method for characterization of low-dose interactive mixtures2013Inngår i: Pharmaceutical development and technology (Print), ISSN 1083-7450, E-ISSN 1097-9867, Vol. 18, nr 6, 1366-1371 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study investigated a sieve classification method for evaluating carrier materials and particle size fractions, which could be a valuable tool in the early development of pharmaceutical dosage forms containing low-dose interactive mixtures. When developing new products based on interactive mixtures, it is essential to ensure that the drug particles are successfully deagglomerated and have adhered to the carrier particles. In this study, the effect on the demixing potential (DP) of low-dose interactive mixtures was assessed for various carrier particle sizes and surface textures. The model drug used was sodium salicylate and the tested carriers were lactose, mannitol, and isomalt. The results showed that the lowest DPs, i.e. the most mechanically stable mixtures, were obtained with lactose. Furthermore, for interactive mixtures, small carrier particles and/or a narrow carrier particle size range are essential for obtaining a low DP and high homogeneity. Calculation of the DP provided a reliable estimate of the quality of the low-dose interactive mixtures used in this study.

  • 8.
    Bäckström, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Ekman, Elizabet
    Regional Pharmacovigilance Unit, Skanes University hospital, CKFL, Lund, Sweden.
    Attitudes among nurses in Sweden and factors for their reporting of adverse drug reactions2011Inngår i: Abstracts 27th International Conference on Pharmacoepidemiology & Therapeutic Risk Management Hyatt Regency Chicago: Chicago, Illinois, USA August 14–17, 2011, Wiley , 2011, Vol. 20, S202-S203 s.Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Background: Adverse drug reactions (ADRs) is a common cause for hospitalization and death. Spontaneous reporting of ADRs remains as one of the cornerstones in post marketing drug safety surveillance. In March 2007 the Medical Product Agency (MPA) in Sweden decided to also accept reports of suspected ADRs from all nurses.

    Objectives: This study was designed to investigate attitudes and factors for reporting adverse drug reactions (ADRs) from nurses within the health care system in Sweden.

    Methods: A questionnaire was distributed to 753 randomly selected nurses in Sweden.

    Results: The most important factors in their decision to report as suspected ADRs were the severity, if the drug was newly approved and if the reaction were unusual. The nurses with a shorter professional experience responded to a higher degree than their colleagues that they made other priorities, did not have the time or where unaware/uncertain what and how to report. Almost two - thirds of the responders assessed that they had insufficient pharmacological knowledge. A vast majority (84%) of the responders would prefer a possibility to report a suspected ADR using a web - based formula.

    Conclusions: Nurses in Sweden have a fairly good knowledge about the existing rules for reporting. However, there is room for improvement in some areas. Further education and information is needed.

  • 9. Conaway, H Herschel
    et al.
    Persson, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral cellbiologi.
    Halén, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral cellbiologi.
    Granholm, Susanne
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral cellbiologi.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Pettersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Lie, Anita
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral cellbiologi.
    Lerner, Ulf H
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral cellbiologi.
    Retinoids inhibit differentiation of hematopoietic osteoclast progenitors2009Inngår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 23, nr 10, 3526-3538 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Whether vitamin A promotes skeletal fragility, has no effect on fracture rate, or protects against bone loss is unclear. In the present study, effects of retinoids on osteoclast differentiation in cultured mouse bone marrow cells (BMCs), bone marrow macrophages (BMMs), spleen cells, and RAW264.7 cells were evaluated by analyzing osteoclast formation and expression of genes important in signal transduction and osteoclast function. All-trans-retinoic acid (ATRA) did not stimulate osteoclastogenesis in BMCs, but inhibited hormone and RANKL-induced gene expression and formation of osteoclasts. In BMMs, spleen cells, and RAW264.7 cells, osteoclast differentiation and formation stimulated by M-CSF/RANKL were inhibited (IC(50) = 0.3 nM) by ATRA. The effect was exerted at an early step of RANKL-induced differentiation. ATRA also abolished increases of the transcription factors c-Fos and NFAT2 stimulated by RANKL and suppressed down-regulation of the antiosteoclastogenic transcription factor MafB. By comparing effects of several compounds structurally related to ATRA, as well as by using receptor antagonists, evaluation pointed to inhibition being mediated by RARalpha, with no involvement of PPARbeta/delta. The results suggest that activation of RARalpha by retinoids in myeloid hematopoietic precursor cells decreases osteoclast formation by altering expression of the transcription factors c-Fos, NFAT2, and MafB.

  • 10.
    Conaway, H. Herschel
    et al.
    Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
    Pirhayati, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Molekylär paradontologi.
    Persson, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Molekylär paradontologi.
    Pettersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lindholm, Catharina
    Center for Bone and Arthritis Research at the Institute for Medicine, Sahlgrenska Academy at the University of Gothenburg.
    Henning, Petra
    Center for Bone and Arthritis Research at the Institute for Medicine, Sahlgrenska Academy at the University of Gothenburg.
    Tuckermann, Jan
    Tissue-specific Hormone Action, Leibniz Institute for Age Research, Fritz Lipmann Institute, D-07745 Jena, Germany.
    Lerner, Ulf H.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Molekylär paradontologi.
    Retinoids Stimulate Periosteal Bone Resorption by Enhancing the Protein RANKL: a Response Inhibited by Monomeric Glucocorticoid Receptor2011Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 286, 31425-31436 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Increased vitamin A (retinol) intake has been suggested to increase bone fragility. In the present study, we investigated effects of retinoids on bone resorption in cultured neonatal mouse calvarial bones and their interaction with glucocorticoids (GC). All-trans-retinoic acid (ATRA), retinol, retinalaldehyde, and 9-cis-retinoic acid stimulated release of (45)Ca from calvarial bones. The resorptive effect of ATRA was characterized by mRNA expression of genes associated with osteoclast differentiation, enhanced osteoclast number, and bone matrix degradation. In addition, the RANKL/OPG ratio was increased by ATRA, release of (45)Ca stimulated by ATRA was blocked by exogenous OPG, and mRNA expression of genes associated with bone formation was decreased by ATRA. All retinoid acid receptors (RAR alpha/beta/gamma) were expressed in calvarial bones. Agonists with affinity to all receptor subtypes or specifically to RAR alpha enhanced the release of (45)Ca and mRNA expression of Rankl, whereas agonists with affinity to RAR beta/gamma or RAR gamma had no effects. Stimulation of Rankl mRNA by ATRA was competitively inhibited by the RAR alpha antagonist GR110. Exposure of calvarial bones to GC inhibited the stimulatory effects of ATRA on 45Ca release and Rankl mRNA and protein expression. This inhibitory effect was reversed by the glucocorticoid receptor (GR) antagonist RU 486. Increased Rankl mRNA stimulated by ATRA was also blocked by GC in calvarial bones from mice with a GR mutation that blocks dimerization (GR(dim) mice). The data suggest that ATRA enhances periosteal bone resorption by increasing the RANKL/OPG ratio via RAR alpha receptors, a response that can be inhibited by monomeric GR.

  • 11.
    Dahlqvist, Rune
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    [Knowledge on feet of clay]2008Inngår i: Läkartidningen, ISSN 0023-7205, Vol. 105, nr 19, 1405-1406 s.Artikkel i tidsskrift (Annet vitenskapelig)
  • 12.
    Dahlqvist, Rune
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    The European Journal of Clinical Pharmacology: 40 years young and going strong.2008Inngår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 64, nr 2, 95-6 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 13. de Batlle, J.
    et al.
    Ferrari, P.
    Chajes, V.
    Park, J. Y.
    Slimani, N.
    McKenzie, F.
    Overvad, K.
    Roswall, N.
    Tjønneland, A.
    Boutron-Ruault, M. C.
    Clavel-Chapelon, F.
    Fagherazzi, G.
    Katzke, V.
    Kaaks, R.
    Bergmann, M. M.
    Trichopoulou, A.
    Lagiou, P.
    Trichopoulos, D.
    Palli, D.
    Sieri, S.
    Panico, S.
    Tumino, R.
    Vineis, P.
    Bueno-de-Mesquita, H. B.
    Peeters, P. H.
    Hjartåker, A.
    Engeset, D.
    Weiderpass, E.
    Sánchez, S.
    Travier, N.
    Sanchez, M. J.
    Amiano, P.
    Chirlaque, M. D.
    Barricarte Gurrea, A.
    Khaw, K. T.
    Key, T. J.
    Bradbury, K. E.
    Ericson, U.
    Sonestedt, E.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Schneede, Jörn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Riboli, E.
    Romieu, I.
    Dietary folate intake and breast cancer risk: European prospective investigation into cancer and nutrition2015Inngår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 107, nr 1, dju367Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is limited evidence on the association between dietary folate intake and the risk of breast cancer (BC) by hormone receptor expression in the tumors. We investigated the relationship between dietary folate and BC risk using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 367993 women age 35 to 70 years were recruited in 10 European countries. During a median follow-up of 11.5 years, 11575 women with BC were identified. Dietary folate intake was estimated from country-specific dietary questionnaires. Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk. BC tumors were classified by receptor status. Subgroup analyses were performed by menopausal status and alcohol intake. Intake of other B vitamins was considered. All statistical tests were two-sided. A borderline inverse association was observed between dietary folate and BC risk (hazard ratio comparing top vs bottom quintile [HRQ5-Q1] = 0.92, 95% CI = 0.83 to 1.01, P (trend) = .037). In premenopausal women, we observed a statistically significant trend towards lower risk in estrogen receptor-negative BC (HRQ5-Q1 = 0.66, 95% CI = 0.45 to 0.96, P (trend) = .042) and progesterone receptor-negative BC (HRQ5-Q1 = 0.70, 95% CI = 0.51 to 0.97, P (trend) = .021). No associations were found in postmenopausal women. A 14% reduction in BC risk was observed when comparing the highest with the lowest dietary folate tertiles in women having a high (> 12 alcoholic drinks/week) alcohol intake (HRT3-T1 = 0.86, 95% CI = 0.75 to 0.98, P (interaction) = .035). Higher dietary folate intake may be associated with a lower risk of sex hormone receptor-negative BC in premenopausal women.

  • 14. de Vogel, Stefan
    et al.
    Schneede, Jörn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Ueland, Per Magne
    Vollset, Stein Emil
    Meyer, Klaus
    Fredriksen, Åse
    Midttun, Øivind
    Bjørge, Tone
    Kampman, Ellen
    Bretthauer, Michael
    Hoff, Geir
    Biomarkers related to one-carbon metabolism as potential risk factors for distal colorectal adenomas2011Inngår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, nr 8, 1726-1735 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Efficient one-carbon metabolism, which requires adequate supply of methyl group donors and B-vitamins, may protect against colorectal carcinogenesis. However, plasma folate and vitamins B2 and B12 have inconsistently been associated with colorectal cancer risk, and there have been no previous studies relating plasma concentrations of methionine, choline, and betaine to this outcome.

    METHODS: This study comprised 10,601 individuals, 50 to 64 years of age, participating in the Norwegian Colorectal Cancer Prevention (NORCCAP) screening study. Using logistic regression analyses, we crosssectionally investigated associations between distal colorectal adenoma occurrence-potential precursor lesions of colorectal carcinomas-and plasma concentrations of methyl group donors and B-vitamins, and polymorphisms of genes related to one-carbon metabolism.

    RESULTS: Screening revealed 1,809 subjects (17.1%) with at least one adenoma. The occurrence of high-risk adenomas (observed in 421 subjects) was inversely associated with plasma concentrations of methionine (highest versus lowest quartile: odds ratio (OR) = 0.61; 95% confidence interval (CI) = 0.45-0.83), betaine: OR = 0.74; 95% CI = 0.54-1.02, the vitamin B2 form flavin-mononucleotide (FMN): OR = 0.65; 95% CI = 0.49-0.88, and the vitamin B6 form pyridoxal 5'-phosphate (PLP): OR = 0.69; 95% CI = 0.51-0.95, but not with folate, choline, vitamin B12 concentrations, or with the studied polymorphisms. High methionine concentration in combination with high vitamin B2 or B6 concentrations was associated with lower occurrence of high-risk adenomas compared with these factors individually.

    CONCLUSIONS: High plasma concentrations of methionine and betaine, and vitamins B2 and B6 may reduce risk of developing colorectal adenomas.

    IMPACT: In addition to B-vitamins, methyl group donors such as methionine and betaine may play a role in colorectal carcinogenesis.

  • 15.
    Edstedt, Bertil
    et al.
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Jansson, J-H
    Boman, K
    Inga vetenskapliga skäl längre för B-vitaminer till hjärt-kärlsjuka2006Inngår i: Läkartidningen, Vol. 45, nr 103, 3464-3466 s.Artikkel i tidsskrift (Annet vitenskapelig)
  • 16. Ekman, Elisabet
    et al.
    Bäckström, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Attitudes among hospital physicians to the reporting of adverse drug reactions in Sweden2009Inngår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 65, nr 1, 43-46 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: This study was designed to investigate attitudes to and incentive for reporting adverse drug reactions (ADRs) in general and towards nurses as reporters of ADRs in particular in a sample of hospital physicians. METHOD: A questionnaire was sent to 1,201 randomly selected hospital physicians. RESULTS: The main factors for the decision to report an ADR were the severity of the reaction, a reaction to a new drug, and an unusual reaction. The most important factor for refraining from reporting was that the reaction was well known. There were no significant differences between males and females or between age groups in these aspects. A majority were positive or neutral to nurses as reporters. Only 6% stated that their willingness to report ADRs would be affected in a negative way if nurses were involved in the program for reporting. CONCLUSIONS: The results of this survey showed that inclusion of hospital nurses as reporters will not decrease the reporting rate from the physicians.

  • 17.
    Ekstedt, Bertil
    et al.
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Mjörndal, Tom
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Interaction between Trombyl and ACE inhibitor2006Inngår i: Läkartidningen, Vol. 103, nr 48, 3842- s.Artikkel i tidsskrift (Fagfellevurdert)
  • 18.
    Englund, Undis
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Littbrand, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Sondell, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Bucht, Gustaf
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Pettersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    The beneficial effects of exercise on BMC are lost after cessation: a 5-year follow-up in older post-menopausal women2009Inngår i: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 19, nr 3, 381-388 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study investigates whether the positive effects on bone mineral density (BMD, g/cm2) and neuromuscular function following a combined weight-bearing program are sustained in older women, a longer period after cessation of training. Thirty-four women (18 exercisers and 16 controls) aged 73–88 years, who completed a 12-month randomized-controlled trial, were invited to a 5-year follow-up assessment of BMD and neuromuscular function. Both groups sustained significant losses in BMD of the femoral neck, trochanter, and Ward's triangle during the follow-up period. Significant losses were also seen in all neuromuscular function tests. The inter-group change was, however, significant only for maximal walking speed where the exercise group had a significantly greater loss. In conclusion, this study suggests that gains in bone density and neuromuscular functions achieved by training are lost after cessation of training. Continuous high-intensity weight-loading physical activity is probably necessary to preserve bone density and neuromuscular function in older women.

  • 19.
    Englund, Undis
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Littbrand, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Sondell, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Pettersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Bucht, Gustaf
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    A 1-year combined weight-bearing training program is beneficial for bone mineral density and neuromuscular function in older women2005Inngår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 16, nr 9, 1117-1123 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Forty-eight community living women 66–87 years old volunteered to participate in a 12-month prospective, randomized, controlled, trial. The aim was to determine if a combined weight-bearing training program twice a week would be beneficial to bone mineral density and neuromuscular function. The participants were pairwise age-matched and randomly assigned to either an exercise group (n=24) or a control group (n=24). Twenty-one subjects in the intervention group and 19 in the control group completed the study. The exercise program lasted for 50 min and consisted of a combination of strengthening, aerobic, balance and coordination exercises. The mean percentage of scheduled sessions attended for the exercise group was 67%. At the completion of the study, the intervention group showed significant increments in bone mineral density of the Wards triangle (8.4%, P<0.01) as well as improvement in maximum walking speed (11.4%, P<0.001) and isometric grip strength (9.9%, P<0.05), as compared to the control group. The conclusion was that a combined weight-bearing training program might reduce fracture risk factors by improving bone density as well as muscle strength and walking ability. This program could be suitable for older community living women in general, and might, therefore, have important implications for fracture prevention.

  • 20.
    Englund, Undis
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nilsson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Bucht, Gustaf
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Björnstig, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Pettersson Kymmer, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Physical activity in middle-aged women and hip fracture risk: the UFO study2011Inngår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 22, nr 2, 499-505 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Summary: In a population-based case-control study, we demonstrate that middle-aged women who were active with walking or in different physical spare time activities were at lower risk of later sustaining a hip fracture compared to more sedentary women.

    Introduction: In middle-aged women participating in the Umeå Fracture and Osteoporosis (UFO) study, we investigated whether physical activity is associated with a subsequent decreased risk of sustaining a hip fracture.

    Methods: The UFO study is a nested case-control study investigating associations between bone markers, lifestyle, and osteoporotic fractures. We identified 81 female hip fracture cases that had reported lifestyle data before they sustained their fracture. Each case was compared with two female controls who were identified from the same cohort and matched for age and week of reporting data, yielding a total cohort of 237 subjects. Mean age at baseline was 57.2 ± 5.0 years, and mean age at fracture was 65.4 ± 6.4 years.

    Results: Conditional logistic regression analysis with adjustments for height, weight, smoking, and menopausal status showed that subjects who were regularly active with walking or had a moderate or high frequency of physical spare time activities (i.e. berry/mushroom picking and snow shovelling) were at reduced risk of sustaining a hip fracture (OR 0.14; 95% CI; 0.05–0.53 for walking and OR 0.19; 95% CI; 0.08–0.46, OR 0.17, 95% CI; 0.05–0.64 for moderate and high frequency of spare time activities, respectively) compared to more sedentary women.

    Conclusion: An active lifestyle in middle age seems to reduce the risk of future hip fracture. Possible mechanisms may include improved muscle strength, coordination, and balance resulting in a decreased risk of falling and perhaps also direct skeletal benefits.

  • 21.
    Englund, Undis
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nilsson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Bergström, Ulrica
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Pettersson Kymmer, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Active commuting reduces the risk of wrist fractures in middle-aged women: the UFO study2013Inngår i: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 24, nr 2, 533-540 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Middle-aged women with active commuting had significantly lower risk for wrist fracture than women commuting by car/bus.

    INTRODUCTION: Our purpose was to investigate whether a physically active lifestyle in middle-aged women was associated with a reduced risk of later sustaining a low-trauma wrist fracture.

    METHODS: The Umeå Fracture and Osteoporosis (UFO) study is a population-based nested case-control study investigating associations between lifestyle and fragility fractures. From a cohort of ~35,000 subjects, we identified 376 female wrist fracture cases who had reported data regarding their commuting habits, occupational, and leisure physical activity, before they sustained their fracture. Each fracture case was compared with at least one control drawn from the same cohort and matched for age and week of reporting data, yielding a total of 778 subjects. Mean age at baseline was 54.3 ± 5.8 years, and mean age at fracture was 60.3 ± 5.8 years.

    RESULTS: Conditional logistic regression analysis with adjustments for height, body mass index, smoking, and menopausal status showed that subjects with active commuting (especially walking) were at significantly lower risk of sustaining a wrist fracture (OR 0.48; 95 % CI 0.27-0.88) compared with those who commuted by car or bus. Leisure time activities such as dancing and snow shoveling were also associated with a lower fracture risk, whereas occupational activity, training, and leisure walking or cycling were unrelated to fracture risk.

    CONCLUSION: This study suggests that active commuting is associated with a lower wrist fracture risk, in middle-aged women.

  • 22. Estrada, Karol
    et al.
    Styrkarsdottir, Unnur
    Evangelou, Evangelos
    Hsu, Yi-Hsiang
    Duncan, Emma L
    Ntzani, Evangelia E
    Oei, Ling
    Albagha, Omar ME
    Amin, Najaf
    Kemp, John P
    Koller, Daniel L
    Li, Guo
    Liu, Ching-Ti
    Minster, Ryan L
    Moayyeri, Alireza
    Vandenput, Liesbeth
    Willner, Dana
    Xiao, Su-Mei
    Yerges-Armstrong, Laura M
    Zheng, Hou-Feng
    Alonso, Nerea
    Eriksson, Joel
    Kammerer, Candace M
    Kaptoge, Stephen K
    Leo, Paul J
    Thorleifsson, Gudmar
    Wilson, Scott G
    Wilson, James F
    Aalto, Ville
    Alen, Markku
    Aragaki, Aaron K
    Aspelund, Thor
    Center, Jacqueline R
    Dailiana, Zoe
    Duggan, David J
    Garcia, Melissa
    Garcia-Giralt, Natàlia
    Giroux, Sylvie
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hocking, Lynne J
    Husted, Lise Bjerre
    Jameson, Karen A
    Khusainova, Rita
    Kim, Ghi Su
    Kooperberg, Charles
    Koromila, Theodora
    Kruk, Marcin
    Laaksonen, Marika
    Lacroix, Andrea Z
    Lee, Seung Hun
    Leung, Ping C
    Lewis, Joshua R
    Masi, Laura
    Mencej-Bedrac, Simona
    Nguyen, Tuan V
    Nogues, Xavier
    Patel, Millan S
    Prezelj, Janez
    Rose, Lynda M
    Scollen, Serena
    Siggeirsdottir, Kristin
    Smith, Albert V
    Svensson, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Trompet, Stella
    Trummer, Olivia
    van Schoor, Natasja M
    Woo, Jean
    Zhu, Kun
    Balcells, Susana
    Brandi, Maria Luisa
    Buckley, Brendan M
    Cheng, Sulin
    Christiansen, Claus
    Cooper, Cyrus
    Dedoussis, George
    Ford, Ian
    Frost, Morten
    Goltzman, David
    González-Macías, Jesús
    Kähönen, Mika
    Karlsson, Magnus
    Khusnutdinova, Elza
    Koh, Jung-Min
    Kollia, Panagoula
    Langdahl, Bente Lomholt
    Leslie, William D
    Lips, Paul
    Ljunggren, Osten
    Lorenc, Roman S
    Marc, Janja
    Mellström, Dan
    Obermayer-Pietsch, Barbara
    Olmos, José M
    Pettersson-Kymmer, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Reid, David M
    Riancho, José A
    Ridker, Paul M
    Rousseau, François
    Lagboom, P Eline S
    Tang, Nelson LS
    Urreizti, Roser
    Van Hul, Wim
    Viikari, Jorma
    Zarrabeitia, María T
    Aulchenko, Yurii S
    Castano-Betancourt, Martha
    Grundberg, Elin
    Herrera, Lizbeth
    Ingvarsson, Thorvaldur
    Johannsdottir, Hrefna
    Kwan, Tony
    Li, Rui
    Luben, Robert
    Medina-Gómez, Carolina
    Th Palsson, Stefan
    Reppe, Sjur
    Rotter, Jerome I
    Sigurdsson, Gunnar
    van Meurs, Joyce BJ
    Verlaan, Dominique
    Williams, Frances MK
    Wood, Andrew R
    Zhou, Yanhua
    Gautvik, Kaare M
    Pastinen, Tomi
    Raychaudhuri, Soumya
    Cauley, Jane A
    Chasman, Daniel I
    Clark, Graeme R
    Cummings, Steven R
    Danoy, Patrick
    Dennison, Elaine M
    Eastell, Richard
    Eisman, John A
    Gudnason, Vilmundur
    Hofman, Albert
    Jackson, Rebecca D
    Jones, Graeme
    Jukema, J Wouter
    Khaw, Kay-Tee
    Lehtimäki, Terho
    Liu, Yongmei
    Lorentzon, Mattias
    McCloskey, Eugene
    Mitchell, Braxton D
    Nandakumar, Kannabiran
    Nicholson, Geoffrey C
    Oostra, Ben A
    Peacock, Munro
    Pols, Huibert AP
    Prince, Richard L
    Raitakari, Olli
    Reid, Ian R
    Robbins, John
    Sambrook, Philip N
    Sham, Pak Chung
    Shuldiner, Alan R
    Tylavsky, Frances A
    van Duijn, Cornelia M
    Wareham, Nick J
    Cupples, L Adrienne
    Econs, Michael J
    Evans, David M
    Harris, Tamara B
    Kung, Annie Wai Chee
    Psaty, Bruce M
    Reeve, Jonathan
    Spector, Timothy D
    Streeten, Elizabeth A
    Zillikens, M Carola
    Thorsteinsdottir, Unnur
    Ohlsson, Claes
    Karasik, David
    Richards, J Brent
    Brown, Matthew A
    Stefansson, Kari
    Uitterlinden, André G
    Ralston, Stuart H
    Ioannidis, John PA
    Kiel, Douglas P
    Rivadeneira, Fernando
    Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture2012Inngår i: Nature Genetics, ISSN 1061-4036, Vol. 44, 491-501 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

  • 23. Eussen, Simone JPM
    et al.
    Nilsen, Roy M
    Midttun, Oivind
    Hustad, Steinar
    IJssennagger, Noortje
    Meyer, Klaus
    Fredriksen, Ase
    Ulvik, Arve
    Ueland, Per M
    Brennan, Paul
    Johansson, Mattias
    Bueno-de-Mesquita, Bas
    Vineis, Paolo
    Chuang, Shu-Chun
    Boutron-Ruault, Marie Christine
    Dossus, Laure
    Perquier, Florence
    Overvad, Kim
    Teucher, Birgit
    Grote, Verena A
    Trichopoulou, Antonia
    Adarakis, George
    Plada, Maria
    Sieri, Sabina
    Tumino, Rosario
    Santucci de Magistris, Maria
    Ros, Martine M
    Peeters, Petra HM
    Luisa Redondo, Maria
    Zamora-Ros, Raul
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Sonestedt, Emily
    Ericson, Ulrika
    Schneede, Jörn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wark, Petra A
    Gallo, Valentina
    Norat, Teresa
    Riboli, Elio
    Vollset, Stein Emil
    North-south gradients in plasma concentrations of B-vitamins and other components of one-carbon metabolism in Western Europe: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study2013Inngår i: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 110, nr 2, 363-374 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Different lifestyle patterns across Europe may influence plasma concentrations of B-vitamins and one-carbon metabolites and their relation to chronic disease. Comparison of published data on one-carbon metabolites in Western European regions is difficult due to differences in sampling procedures and analytical methods between studies. The present study aimed, to compare plasma concentrations of one-carbon metabolites in Western European regions with one laboratory performing all biochemical analyses. We performed the present study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort among 5446 presumptively healthy individuals. Quantile regression was used to compare sex-specific median concentrations between Northern (Denmark and Sweden), Central (France, Germany, The Netherlands and United Kingdom) and Southern (Greece, Spain and Italy) European regions. The lowest folate concentrations were observed in Northern Europe (men, 10.4 nmol/l; women, 10.7 nmol/l) and highest concentrations in Central Europe. Cobalamin concentrations were slightly higher in Northern Europe (men, 330 pmol/l; women, 352 pmol/l) compared with Central and Southern Europe, but did not show a clear north-south gradient. Vitamin B-2 concentrations were highest in Northern Europe (men, 22.2 nmol/l; women, 26.0 nmol/l) and decreased towards Southern Europe (P-trend < 0.001). Vitamin B-6 concentrations were highest in Central Europe in men (77.3 nmol/l) and highest in the North among women (70.4 nmol/l), with decreasing concentrations towards Southern Europe in women (P-trend < 0.001). In men, concentrations of serine, glycine and sarcosine increased from the north to south. In women, sarcosine increased from Northern to Southern Europe. These findings may provide relevant information for the study of regional differences of chronic disease incidence in association with lifestyle.

  • 24. Filippov, Andrey
    et al.
    Munavirov, Bulat
    Sparrman, Tobias
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Ishmuhametova, Valentina
    Rudakova, Maya
    Shriram, Prashant
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Tavelin, Staffan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Interaction of a poly(acrylic acid) oligomer with dimyristoylphosphatidylcholine bilayers2011Inngår i: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 27, nr 7, 3754-3761 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We studied the influence of 5 kDa poly(acrylic acid) (PAA) on the phase state, thermal properties, and lateral diffusion in bilayered systems of dimyristoylphosphatidylcholine (DMPC) using (31)P NMR spectroscopy, differential scanning calorimetry (DSC), (1)H NMR with a pulsed field gradient, and (1)H nuclear Overhauser enhancement spectroscopy (NOESY). The presence of PAA does not change the lamellar structure of the system. (1)H MAS NOESY cross-peaks observed for the interaction between lipid headgroups and polyion protons demonstrated only surface PAA-biomembrane interaction. Small concentrations of PAA (up to ∼4 mol %) lead to the appearance of a new lateral phase with a higher main transition temperature, a lower cooperativity, and a lower enthalpy of transition. Higher concentrations lead to the disappearance of measurable thermal effects. The lateral diffusion coefficient of DMPC and the apparent activation energy of diffusion gradually decreased at PAA concentrations up to around 4 mol %. The observed effects were explained by the formation of at least two types of PAA-DMPC lateral complexes as has been described earlier (Fujiwara, M.; Grubbs, R. H.; Baldeschwieler, J. D. J. Colloid Interface Sci., 1997, 185, 210). The first one is characterized by a stoichiometry of around 28 lipids per polymer, which corresponds to the adsorption of the entire PAA molecule onto the membrane. Lipid molecules of the complex are exchanged with the "pure" lipid bilayer, with the lifetime of the complex being less than 0.1 s. The second type of DMPC-PAA complex is characterized by a stoichiometry of 6 to 7 lipids per polymer and contains PAA molecules that are only partially adsorbed onto the membrane. A decrease in the DMPC diffusion coefficient and activation energy for diffusion in the presence of PAA was explained by the formation of a new cooperative unit for diffusion, which contains the PAA molecule and several molecules of lipids.

  • 25.
    Glader, Eva-Lotta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sjölander, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Eriksson, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lundberg, Michael
    Persistent use of secondary preventive drugs declines rapidly during the first 2 years after stroke.2010Inngår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 41, nr 2, 397-401 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND PURPOSE: To prevent new cardiovascular events after stroke, prescribed preventive drugs should be used continuously. This study measures persistent use of preventive drugs after stroke and identifies factors associated with persistence.

    METHODS: A 1-year cohort (21,077 survivors) from Riks-Stroke, the Swedish Stroke Register, was linked to the Swedish Prescribed Drug Register.

    RESULTS: The proportion of patients who were persistent users of drugs prescribed at discharge from hospital declined progressively over the first 2 years to reach 74.2% for antihypertensive drugs, 56.1% for statins, 63.7% for antiplatelet drugs, and 45.0% for warfarin. For most drugs, advanced age, comorbidity, good self-perceived health, absence of low mood, acute treatment in a stroke unit, and institutional living at follow-up were independently associated with persistent medication use.

    CONCLUSIONS: Persistent secondary prevention treatment declines rapidly during the first 2 years after stroke, particularly for statins and warfarin. Effective interventions to improve persistent secondary prevention after stroke need to be developed.

  • 26. Gu, Qiang
    et al.
    Kong, Yan
    Schneede, Jörn
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Xiao, Ying-Bin
    Chen, Lin
    Zhong, Qian-Jin
    Wang, Xue-Feng
    Hao, Jia
    Chen, Bai-Cheng
    Chen, Jing-Jin
    VKORC1-1639G>A, CYP2C9, EPHX1691A>G genotype, body weight, and age are important predictors for warfarin maintenance doses in patients with mechanical heart valve prostheses in southwest China2010Inngår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 66, nr 12, 1217-1227 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There were great interindividual differences in warfarin maintenance dosage (ranging from 0.6 to 8.4 mg/day) among the 127 patients with mechanical heart valve prostheses. VKORC1-1639G>A, CYP2C9, EPHX1691A>G polymorphism, body weight, and age were found to affect the dose demands. Multiple linear regression models incorporating genetic polymorphisms of VKORC1, CYP2C9, EPHX1691A>G, and the nongenetic factors of age and body weight were developed, and explained up to 76.8% of the total variation (adjusted R (2) of 0.743) in warfarin maintenance doses in southwest Chinese patients with mechanical heart valve prostheses.

  • 27. Gudex, Claire
    et al.
    Hoffmann, Mikael
    Brørs, Odd
    Dahlqvist, Rune
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Praktiserende lægers opfattelse afInstitut for Rationel Farmakoterapi [GPs' perceptions of the Institute for Rational Pharmacotherapy]2009Inngår i: Ugeskrift for laeger, ISSN 1603-6824, Vol. 171, nr 7, 522-526 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: A questionnaire study was conducted among Danish general practitioners (GPs) as part of an international evaluation of the Institute for Rational Pharmacotherapy (IRF). The aim was to investigate GPs' use and opinion of the IRF's activities. MATERIAL AND METHODS: A questionnaire was sent to a random sample of 500 GPs, who were asked about their level of knowledge and frequency of use of IRF's activities, as well as their opinion on the relevance, credibility and independence of the IRF's activities. RESULTS: The response rate was 59%. IRF is generally not the first source of information about new drugs, but is frequently used in the search for information about comparability between drugs and in relation to sudden drug warnings. IRF's Rational Pharmacotherapy bulletin and its GP courses, which nine out of ten GPs knew about, were considered to be highly relevant by 80% and 71%, respectively. All of IRF's activities were considered highly credible. Most GPs felt that the IRF's information increased their confidence in prescribing decisions (84%) and supported them in their role as a GP (88%). CONCLUSION: IRF's activities support the GP's prescribing role through the production of credible, neutral and evidence-based pharmacotherapeutic information that is not available elsewhere. IRF could further refine its dissemination methods, however, in order to reach more GPs and to increase the use of its information.

  • 28.
    Gustafsson, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Sandman, Per-Olof
    Karlsson, Stig
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Lövheim, Hugo
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Association between behavioral and psychological symptoms and psychotropic drug use among old people with cognitive impairment living in geriatric care settings2013Inngår i: International psychogeriatrics, ISSN 1041-6102, E-ISSN 1741-203X, Vol. 25, nr 9, 1415-23 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Behavioral and psychological symptoms are common among cognitively impaired individuals and psychotropic drugs are widely used for their treatment. The aim of this study was to describe the prevalence and associated factors of psychotropic and anti-dementia drug use among old people with cognitive impairment living in geriatric care settings. Methods: The study comprised 2,019 cognitively impaired people living in geriatric care units in the county of Västerbotten, Sweden. Data concerning psychotropic and anti-dementia drug use, function in activities of daily living, cognitive function, and prevalence of behavioral and psychological symptoms were collected, using the Multi-Dimensional Dementia Assessment Scale. Results: Of the study population, 1,442 individuals (71%) were prescribed at least one psychotropic drug (antidepressants (49%), anxiolytics, hypnotics, and sedatives (36%), antipsychotics (25%)). Furthermore, 363 individuals (18%) received anti-dementia drugs. Associations between various behavioral and psychological symptoms were found for all psychotropic drug classes and anti-dementia drugs. Verbally disruptive/attention-seeking behavior was associated with all psychotropic drugs. Use of antipsychotics was associated with several behavioral and psychological symptoms, including aggressive behavior. Conclusion: The associations between behavioral and psychological symptoms and psychotropic drug use found in this study indicate that these drugs are prescribed to treat behavioral and psychological symptoms among cognitively impaired individuals despite limited evidence of their efficacy. Given the significant risk of adverse effects among old people with cognitive impairment, it is important to ensure that any medication used is both appropriate and safe.

  • 29. Hagnelius, Nils-Olof
    et al.
    Wahlund, Lars-Olof
    Schneede, Jörn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Nilsson, Torbjörn K
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Blood Concentrations of Homocysteine and Methylmalonic Acid among Demented and Non-Demented Swedish Elderly with and without Home Care Services and Vitamin B(12) Prescriptions2012Inngår i: Dementia and geriatric cognitive disorders extra, ISSN 1664-5464, Vol. 2, nr 1, 387-99 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND AIMS: Total plasma homocysteine (tHcy) has been suggested as a risk factor of dementia. Our aim was to investigate potential differences in tHcy status in relation to the prescription of vitamin B(12) and dementia diagnosis. We examined whether vitamin B(12) prescriptions, a family history of dementia, or the need for home care service might be associated with tHcy values. METHODS: A cross-sectional monocenter study comprising 926 consecutive subjects attending our Memory Care Unit was conducted. RESULTS: Demented subjects being prescribed vitamin B(12) had higher serum vitamin B(12) (p = 0.025) but also higher tHcy (p < 0.001) and serum methylmalonate (p = 0.032), and lower serum folate (p < 0.001) than those who did not receive vitamin B(12) prescriptions. tHcy levels were significantly higher in non-demented subjects receiving home care service (p = 0.007). This group also had lower serum albumin (dementia: p < 0.001; non-dementia: p = 0.004). There was no difference in renal function (estimated glomerular filtration rate) in demented or non-demented subjects with or without vitamin B(12) prescriptions (dementia with/without vitamin B(12) prescription: p = 0.561; non-dementia with/without vitamin B(12) prescription: p = 0.710). CONCLUSION: Despite vitamin B(12) prescriptions, demented subjects had higher tHcy and methylmalonate values. The elevated metabolite values could not be explained by differences in renal function. Thus, elderly subjects on vitamin B(12) prescription appear to have unmet nutritional needs.

  • 30. Henning, P.
    et al.
    Kindlund, B.
    Pettersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Conaway, H. H.
    Lerner, Ulf H
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Molekylär paradontologi.
    Inhibition of osteoclast formation in human peripheral CD14+cells by vitamin A2012Inngår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, nr Supplement 1, S92-S92 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 31. Henrohn, Dan
    et al.
    Sandqvist, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Hedeland, Mikael
    Egerod, Hanna
    Bondesson, Ulf
    Wikstrom, Gerhard
    Acute haemodynamic response in relation to plasma vardenafil concentrations in patients with pulmonary hypertension2012Inngår i: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 74, nr 6, 990-998 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS To evaluate the acute haemodynamic effects of a single oral dose of vardenafil and to study the drug concentration in relation to haemodynamic effects in patients with pulmonary hypertension (PH). METHODS Sixteen patients with PH (aged 29-85\ years), received one single oral dose of vardenafil (5, 10 or 20 mg). The haemodynamic effect was assessed over a 60 min period. Vardenafil plasma concentrations were measured after 15, 30, 45 and 60 min using liquid chromatography-tandem mass spectrometry. RESULTS At 60 min a reduction in mPAP with a median % decrease of -20.3% (range -48.3 to 3.0; P < 0.001) and an increase in cardiac output and the cardiac index with a median % change of 10.6% (range -25.0 to 88.1; P = 0.015) and 12.1% (range -24.0 to 94.4; P = 0.01) respectively was observed. The pulmonary vascular resistance (PVR) was reduced with a median % decrease of -28.9% (range -61.5 to -5.9; P < 0.001), and pulmonary selectivity was reflected by a median percent reduction of -16.9% (range -49.0 to 16.5; P = 0.002; n = 14) in the PVR/ systemic vascular resistance ratio. There was a correlation between the plasma concentrations of vardenafil and change in mPAP (r = -0.579, P = 0.019) and between vardenafil concentrations and change in PVR (r = -0.662, P = 0.005). CONCLUSIONS Vardenafil causes rapid changes in cardiopulmonary haemodynamics and there is a correlation between plasma vardenafil drug concentration and the acute changes in mPAP as well as PVR in patients with PH.

  • 32. Hoeyer, K
    et al.
    Olofsson, BO
    Mjörndal, Tom
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Lynoe, N
    The ethics of informed consent in biobankbased research: The Swedish case2005Inngår i: Arch Intern Med, Vol. 165, 97-100 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 33.
    Hoeyer, Klaus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Olofsson, Bert-Ove
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Mjörndal, Tom
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Lynöe, Niels
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    The ethics of research using biobanks: reason to question the importance attributed to informed consent.2005Inngår i: Archives of Internal Medicine, ISSN 0003-9926, E-ISSN 1538-3679, Vol. 165, nr 1, 97-100 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: During the past decade, the use of stored tissue has become an object of increased ethical query. A Swedish biobank and a biotech company have been praised for solving the ethical problems with explicit informed consent procedures, and we decided to investigate donors' perceptions of the system. METHODS: A questionnaire was sent to a randomized sample of 1200 donors who had donated blood and signed informed consent forms. RESULTS: The response rate was 80.9%. Of the respondents, 64.5% were aware that they had consented to donate a blood sample, 55.4% thought that they had consented to donate phenotypic information, and 31.6% believed that they could withdraw their consent. Among respondents, 3.9% considered informing donors about the research objective as the most important ethical issue in relation to biobanks, and 5.6% were unsatisfied with the information they had been given. There was 85.9% acceptance of surrogate decision making by regional research ethics committees. CONCLUSIONS: Considering that the donors in this study were not always aware of their donation but generally were not unsatisfied with the information they had received, and that they did not rate being informed about the research objective as an important issue, informed consent seems to be an inadequate measure of public acceptance of biobank-based research.

  • 34. Hoff, Geir
    et al.
    Grotmol, Tom
    Skovlund, Eva
    Bretthauer, Michael
    Schneede, Jörn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Risk of colorectal cancer seven years after flexible sigmoidoscopy screening: randomised controlled trial2009Inngår i: BMJ. British Medical Journal (International Ed.), ISSN 0959-8146, E-ISSN 1468-5833, Vol. 338, b1846- s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To determine the risk of colorectal cancer after screening with flexible sigmoidoscopy. DESIGN: Randomised controlled trial. SETTING: Population based screening in two areas in Norway-city of Oslo and Telemark county (urban and mixed urban and rural populations). PARTICIPANTS: 55 736 men and women aged 55-64 years. INTERVENTION: Once only flexible sigmoidoscopy screening with or without a single round of faecal occult blood testing (n=13 823) compared with no screening (n=41 913). MAIN OUTCOME MEASURES: Planned end points were cumulative incidence and mortality of colorectal cancer after 5, 10, and 15 years. This first report from the study presents cumulative incidence after 7 years of follow-up and hazard ratio for mortality after 6 years. RESULTS: No difference was found in the 7 year cumulative incidence of colorectal cancer between the screening and control groups (134.5 v 131.9 cases per 100 000 person years). In intention to screen analysis, a trend towards reduced colorectal cancer mortality was found (hazard ratio 0.73, 95% confidence interval 0.47 to 1.13, P=0.16). For attenders compared with controls, a statistically significant reduction in mortality was apparent for both total colorectal cancer (hazard ratio 0.41, 0.21 to 0.82, P=0.011) and rectosigmoidal cancer (0.24, 0.08 to 0.76, P=0.016). CONCLUSIONS: A reduction in incidence of colorectal cancer with flexible sigmoidoscopy screening could not be shown after 7 years' follow-up. Mortality from colorectal cancer was not significantly reduced in the screening group but seemed to be lower for attenders, with a reduction of 59% for any location of colorectal cancer and 76% for rectosigmoidal cancer in per protocol analysis, an analysis prone to selection bias. TRIAL REGISTRATION: Clinical trials NCT00119912.

  • 35. Holme, Oyvind
    et al.
    Loberg, Magnus
    Kalager, Mette
    Bretthauer, Michael
    Hernan, Miguel A.
    Aas, Eline
    Eide, Tor J.
    Skovlund, Eva
    Schneede, Jörn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Tveit, Kjell Magne
    Hoff, Geir
    Effect of Flexible Sigmoidoscopy Screening on Colorectal Cancer Incidence and Mortality A Randomized Clinical Trial2014Inngår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 312, nr 6, 606-615 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    IMPORTANCE

    Colorectal cancer is a major health burden. Screening is recommended in many countries. OBJECTIVE To estimate the effectiveness of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality in a population-based trial. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 100 210 individuals aged 50 to 64 years, identified from the population of Oslo city and Telemark County, Norway. Screening was performed in 1999-2000 (55-64-year age group) and in 2001 (50-54-year age group), with follow-up ending December 31, 2011. Of those selected, 1415 were excluded due to prior colorectal cancer, emigration, or death, and 3 could not be traced in the population registry.

    INTERVENTIONS

    Participants randomized to the screening group were invited to undergo screening. Within the screening group, participants were randomized 1: 1 to receive once-only flexible sigmoidoscopy or combination of once-only flexible sigmoidoscopy and fecal occult blood testing (FOBT). Participants with positive screening test results (cancer, adenoma, polyp >= 10 mm, or positive FOBT) were offered colonoscopy. The control group received no intervention.

    MAIN OUTCOMES AND MEASURES

    Colorectal cancer incidence and mortality.

    RESULTS

    A total of 98 792 participants were included in the intention-to-screen analyses, of whom 78 220 comprised the control group and 20 572 comprised the screening group (10 283 randomized to receive a flexible sigmoidoscopy and 10 289 to receive flexible sigmoidoscopy and FOBT). Adherence with screening was 63%. After a median of 10.9 years, 71 participants died of colorectal cancer in the screening group vs 330 in the control group (31.4 vs 43.1 deaths per 100 000 person-years; absolute rate difference, 11.7 [95% CI, 3.0-20.4]; hazard ratio [HR], 0.73 [95% CI, 0.56-0.94]). Colorectal cancer was diagnosed in 253 participants in the screening group vs 1086 in the control group (112.6 vs 141.0 cases per 100 000 person-years; absolute rate difference, 28.4 [95% CI, 12.1-44.7]; HR, 0.80 [95% CI, 0.70-0.92]). Colorectal cancer incidence was reduced in both the 50-to 54-year age group (HR, 0.68; 95% CI, 0.49-0.94) and the 55-to 64-year age group (HR, 0.83; 95% CI, 0.71-0.96). There was no difference between the flexible sigmoidoscopy only vs the flexible sigmoidoscopy and FOBT screening groups.

    CONCLUSIONS AND RELEVANCE

    In Norway, once-only flexible sigmoidoscopy screening or flexible sigmoidoscopy and FOBT reduced colorectal cancer incidence and mortality on a population level compared with no screening. Screening was effective both in the 50-to 54-year and the 55-to 64-year age groups.

  • 36. Holmgren, Helena M
    et al.
    Schneede, Jörn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Acetylsalicylsyra i låg dos plus naproxen: liten interaktionsrisk i praktiken2011Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, nr 26-28, 1374-1374 s.Artikkel i tidsskrift (Annet vitenskapelig)
  • 37.
    Holmgren, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Schneede, Jörn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    [NSAID can increase the risk of cardiovascular incidents. The risk increase is usually connected to dosage and the length of treatment].2012Inngår i: Läkartidningen, ISSN 0023-7205, Vol. 109, nr 4, 164-164 s.Artikkel i tidsskrift (Annet vitenskapelig)
  • 38. Jonsson, T. B.
    et al.
    Nilsson, Torbjörn K
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Breimer, L. H.
    Schneede, Jörn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Arfvidsson, B.
    Norgren, L.
    Cloxacillin concentrations in serum, subcutaneous fat, and muscle in patients with chronic critical limb ischemia2014Inngår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 70, nr 8, 957-963 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Patients suffering from critical limb ischemia (CLI) have poor wound healing in the ankle and foot areas. Secondary wound infections are frequent and often treated with prolonged courses of antibiotics. This study set out to investigate to what extent the unbound fraction of 4 g of cloxacillin i.v. reaches its target organ in poorly vascularized tissues, i.e., the calf and foot of patients suffering from CLI. Cloxacillin concentrations were measured by HPLC in serum and in microdialysis samples from skin and muscle of the lower part of the calf and as reference subcutaneously at the pectoral level in eight patients suffering from CLI (four males, four females, mean age 78 years, range 66-85 years) and in three healthy controls (two females, one male, mean age 67, range 66-68 years). In patients suffering from CLI, the tissue penetration of cloxacillin after a single 4 g dose was comparable to that of healthy controls, despite impaired blood circulation. The reduced blood flow in the peripheral vessels of the CLI patients presented here apparently is not the rate-limiting factor for delivery or tissue penetration of cloxacillin.

  • 39.
    Kling, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    5-HT2A: a serotonin receptor with a possible role in joint diseases2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background

    Serotonin (5-HT), an amino acid derivative and neurotransmitter, has for long been studied in relation to inflammation. It is an endogenous ligand for several different types of serotonin receptors. The serotonin receptor 5-HT2A has been reported to have a role in the pathophysiology of arthritis in animal experiment models. However, no studies into this subject have been reported in man.

    Objective

    The objectives of this project were firstly, to examine possible associations for the 5-HT2A receptor and also for the gene (HTR2A) encoding for the receptor with arthritis in man and secondly, to explore possible mechanisms underlying such associations.

    Methods

    The density and affinity of platelet 5-HT2A receptors were determined in 43 patients with a common inflammatory joint disease, i. e., rheumatoid arthritis (RA), in comparison with matched controls using a radio-ligand assay. The effects of treatment with prednisolone on 5-HT2A density and affinity were also examined in 27 individuals diagnosed with polymyalgia rheumatica before and after start of treatment. In addition, possible candidate HTR2A genes were studied in relation to RA in two Swedish cohorts incorporating a total of 2450 RA patients. Furthermore, a register study using reports of joint symptoms as adverse drug reactions (ADRs) in the Swedish and the WHO ADR databases was undertaken. The proportion of reports concerning joint symptoms in relation to all ADR reports and to sales figures was analysed for 5-HT2A blocking atypical antidepressant substances compared with another group of antidepressants, i. e., selective serotonin re-uptake inhibitors (SSRIs), used for similar clinical indications.

    Results

    The mean density of 5-HT2A receptors in RA patients was significantly lower than in controls, 45.3 versus 57.4 fmol/mg protein (p = 0.004). There was no significant difference in affinity. Variation of four single nucleotide polymorphisms (SNPs) (rs6314, rs1328674, rs6313 and rs6311) in the HTR2A gene was associated with RA, although not significantly so for all SNPs after testing for multiple comparisons. The proportion of joint symptoms reported as ADRs, relative to all ADRs was significantly higher for the 5-HT2A blocking antidepressants compared with the SSRIs in both databases (p< 0.001). In the Swedish material the comparison of ADRs was also related to sales figures, showing a considerable higher frequency of joint symptoms for the 5-HT2A antagonists (p< 0.001). The density of 5-HT2A receptors increased after treatment with prednisolone in 23 out of 27 individuals. The mean density at baseline was 45.2 versus 64.9 fmol/mg protein at the end of the study (p=0.001). There were no significant differences in affinity during the treatment period, although a low affinity at baseline was a predictor for higher density following treatment with prednisolone.

    Conclusions

    The density of 5-HT2A receptors, reflecting the number of receptors, was markedly reduced in a cohort of patients with RA from Northern Sweden. This may depend, at least in part, on an association between RA and certain HTR2A SNPs. Genetically determined or acquired low levels of accessible 5-HT2A receptors may contribute to susceptibility for development of joint symptoms, not only in RA but more generally, e. g., joint ADRs caused by 5-HT2A blocking atypical antidepressants. The benefits of treatment with glucocorticoids may, at least partially, be mediated by an effect on 5-HT2A receptors.

  • 40.
    Kling, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Danell-Boman, Marit
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap.
    Dahlqvist, Rune
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Association between the use of serotonin receptor 2A-blocking antidepressants and joint disorders2009Inngår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 61, nr 10, 1322-1327 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: There are case reports about antidepressants causing arthritis and arthralgia, and the majority of these reports deal with atypical antidepressants, which are serotonin receptor 2A (5-HT(2A))-blocking substances. The aim of this study was to examine a possible association between joint disorders and the use of 5-HT(2A)-blocking atypical antidepressants.

    METHODS: We performed a retrospective study using reports of adverse drug reactions (ADRs) of 5-HT(2A)-blocking atypical antidepressant substances concerning joint disorders reported to the Swedish Adverse Drug Reactions Committee and the World Health Organization (WHO) Adverse Reactions Database during the period January 1, 1990 to December 31, 2006. The reports of joint disorders were related to sales figures measured as defined daily doses and to the total number of ADR reports.

    RESULTS: In the Swedish material, the 5-HT(2A) antagonists were 45 times more often reported to give joint ADRs when related to sales figures and compared with the selective serotonin reuptake inhibitors (SSRIs; P < 0.001). Joint disorders constituted 6.6% of the total number of reports of possible ADRs for the three 5-HT(2A)-blocking substances mianserin, mirtazapine, and nefazodone compared with 0.5% for the SSRIs (P < 0.001). In the WHO material, the joint disorders constituted 1.3% of all ADRs for the 5-HT(2A)-blocking antidepressants and 0.6% for the SSRIs (P < 0.001).

    CONCLUSION: In this study, joint disorders were considerably more frequently reported ADRs of 5-HT(2A)-blocking antidepressants than of other comparable drugs, suggesting a possible association between the use of 5-HT(2A)-blocking antidepressants and joint disorders.

  • 41.
    Kling, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Mjörndal, Tom
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Glucocorticoid treatment increases density of serotonin 5-HT2A receptors in humans2012Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, nr 7, 1014-1020 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Interactions between the serotonergic system and the hypothalamic–pituitary–adrenal axis have been suggested, albeit the details for such interactions have yet to be established. Animal studies have shown that the density of serotonin 5-HT2A receptors is increased after administration of exogenous glucocorticoids.

    Objective: The objective of this study was to explore possible changes in the pattern of density and affinity of 5-HT2A receptors in humans after treatment with glucocorticoids.

    Methods: Using a radioactive binding assay, the density and affinity (measured as Bmax and Kd) of 5-HT2A serotonin receptors were measured in blood samples drawn from 27 individuals diagnosed with polymyalgia rheumatica and/or giant cell arteritis before and after start of an oral treatment with prednisolone. For each patient Bmax and Kd at baseline before prednisolone treatment were compared with Bmax and Kd in samples drawn at a first and second follow-up clinic visit at an average of 8.8 (±2.5) days and 33.6 (±6.8) days, respectively.

    Results: The density of 5-HT2A receptors increased after treatment in 23 individuals. The mean Bmax value at baseline for all patients was 45.2 fmol/mg protein compared with 64.9 fmol/mg protein in the corresponding samples drawn at the second follow-up visit (p = 0.001). There also was an association between individuals accumulated prednisolone dose and the magnitude of change in Bmax between baseline and the first follow-up visit. Erythrocyte sedimentation rate, platelet count or gender had no influence on the results. There were no significant differences in Kd during the treatment period. However, a low Kd value at baseline was a predictor for an increase in Bmax following treatment.

    Conclusions: The results of this study showed that the density of 5-HT2A serotonin receptors in man is increased after a subchronic treatment with glucocorticoids. The magnitude of the increase appears to be associated with the affinity of 5-HT2A receptors before treatment and the accumulated dose of glucocorticoid early in the treatment period.

  • 42.
    Kling, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Mjörndal, Tom
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sepsis as possible adverse drug reaction in patient with rheumatoid arthritis treated with TNF-alfa antagonists2004Inngår i: Journal of clinical rheumatology, Vol. 3, 119-229 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 43.
    Kling, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap.
    Mjörndal, Tom
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Decreased density of serotonin 5-HT2A receptors in rheumatoid arthritis2006Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 65, nr 6, 816-819 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Animal studies have indicated that 5-HT2A receptors could play a role in arthritic diseases.                             

    Objective: To analyse the binding properties of 5-HT2A receptors in patients with rheumatoid arthritis.                             

    Methods: Using a radioactive binding assay, 43 patients with rheumatoid arthritis were compared with 49 sex and age matched controls for density and affinity (measured as Bmax and Kd) of 5-HT2A serotonin receptors. Genotyping, using polymerase chain reaction, was undertaken to exclude the possibility that differences in the genetic polymorphism T102C for the 5-HT2A receptor determine differences in receptor density.                             

    Results: Mean of Bmax of 5-HT2A receptors in rheumatoid patients was significantly lower than in controls, at 45.3 v 57.4 fmol/mg protein (p = 0.004), but there was no significant difference in Kd. The T102C receptor polymorphism genotypes showed a skewed distribution between the two groups. Even when adjusted for this, there was a significant difference in Bmax between the groups.                             

    Conclusions: The density of 5-HT2A serotonin receptors in patients with rheumatoid arthritis is markedly reduced. This could either reflect a difference involved in the susceptibility to the disease or be a secondary effect of the disease.                             

  • 44.
    Kling, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Seddighzadeh, M
    Arlestig, Lisbeth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Alfredsson, L
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Padyukov, L
    Genetic variations in the serotonin 5-HT2A receptor gene (HTR2A) are associated with rheumatoid arthritis2008Inngår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 67, nr 8, 1111-1115 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: To analyse the association between the genetic polymorphisms within the HTR2A gene for the serotonin receptor and rheumatoid arthritis (RA).

    METHODS: HTR2A gene polymorphisms were analysed in patients with RA and controls from two study populations using PCR based restriction endonuclease mapping or TaqMan allelic discrimination with more than 4000 individuals included in the current study.

    RESULTS: At the discovery stage we detected significant differences in frequency of rs6313 (T102C polymorphism) between the patients with RA and controls (p = 0.006). Following validation with an extended set of single nucleotide polymorphisms (SNPs) and number of DNA samples, a trend in associations in allelic model for SNPs rs6314, rs1328674, rs6313 and rs6311 (p = 0.006, 0.002, 0.006, 0.009) was seen, although it was lost after correction for multi-comparison for all but rs1328674 (empirical p value = 0.021). However, haplotype frequency analysis based on these four SNPs showed significantly low representation of TCTT combination in patients with RA in comparison with controls (3.6% and 5.6%, p<0.001 on chi(2) test, empirical p = 0.004 after 100 000 permutations) and a significantly higher frequency of CTCC combination in patients with RA in comparison with controls (3.6% and 2.2%, p = 0.002 on chi(2) test, empirical p = 0.022 after 100 000 permutations).

    CONCLUSIONS: In our study, genetic polymorphisms at the HTR2A gene are associated with susceptibility for RA, suggesting possible links between the serotonergic system and development of the disease.

  • 45.
    Lakso, Hans-Ake
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Appelblad, Patrik
    Schneede, Jörn
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Quantification of methylmalonic acid in human plasma with hydrophilic interaction liquid chromatography separation and mass spectrometric detection2008Inngår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 54, nr 12, 2028-2035 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Measurement of methylmalonic acid (MMA) in serum or plasma is useful for diagnosing cobalamin deficiency. We developed a method for quantifying MMA in plasma based on hydrophilic interaction liquid chromatography (HILIC) and single-stage negative electrospray ionization (ESI) mass spectrometry.

    Methods: We deproteinized plasma samples (200 microL) with 800 microL acidified acetonitrile containing 0.17 micromol/L deuterated MMA (D(3)-MMA) internal standard, centrifuged the samples, and injected 4 microL of the supernatant into the LC-MS instrument. Separation was achieved within 3 min on a Merck SeQuant ZIC-HILIC column with a mobile phase consisting of 4 volumes acetonitrile plus 1 volume 100 mmol/L ammonium acetate buffer, pH 4.5, at a flow rate of 400 microL/min. Subsequent column washing and reconditioning contributed to a total run time of 10 min. MMA and D(3)-MMA were quantified by single-ion monitoring (m/z 117.2 and 120.2, respectively) in negative ESI mode at a drying-gas flow rate of 10 L/min, 300 degrees C, and a capillary voltage of 3.0 kV.

    Results: The estimated limits of MMA quantification and detection were 0.09 micromol/L and 0.03 micromol/L, respectively, in plasma. The assay was linear to 200 micromol/L. Interassay and intraassay CVs were < or = 5% at all tested concentrations. Recoveries were 90%-93%.

    Conclusions: This robust assay allows analysis of MMA in human plasma without derivatization. Sample preparation is simple and suitable for automation.

  • 46.
    Landerholm, Lisa
    et al.
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Mjörndal, Tom
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Impaired absorption of antibiotics in diarrhea?2006Inngår i: Läkartidningen, Vol. 103, nr 43, 3207-3208 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 47.
    Landerholm, Lisa
    et al.
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Mjörndal, Tom
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Systemic effect of nasal corticoteroids?2006Inngår i: Läkartidningen, Vol. 103, nr 42, 3208-3209 s.Artikkel i tidsskrift (Fagfellevurdert)
  • 48.
    Lennestål, Roland
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Lakso, Hans-Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Nilsson, Mats
    Mjörndal, Tom
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Urine monitoring of diazepam abuse: new intake or not?2008Inngår i: Journal of Analytical Toxicology, ISSN 0146-4760, Vol. 32, nr 6, 402-407 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Testing for drugs-of-abuse in urine is requested for multiple reasons, including legal and workplace policies. Two cases were studied in which there was a suspicion that the patients continued to abuse diazepam, because of repeatedly positive urine samples. In these cases, diazepam metabolites were measured in urine samples by gas or liquid chromatography coupled to mass spectrometry. The concentrations of diazepam metabolites were subsequently creatinine correlated. Very long elimination times were found in the described cases. None of them had in fact ingested diazepam again during the study period. By the use of pharmacogenetic typing, one of the subjects was found to have a slow metabolism for CYP2C9 as well as for CYP2C19. In the second case, there was a possible drug interaction between diazepam and zolpidem.

  • 49.
    Lennestål, Roland
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Otterblad Olausson, Petra
    Källén, Bengt
    Maternal use of antihypertensive drugs in early pregnancy and delivery outcome, notably the presence of congenital heart defects in the infants2009Inngår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 65, nr 6, 615-625 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose To investigate the association between maternal use of antihypertensives in early pregnancy and delivery outcome, notably infant congenital malformations.

    Methods A cohort study of 1,418 women who had used antihypertensive drugs in early pregnancy but had no diabetes diagnosis were identified from the Swedish Medical Birth Register.

    Results There was an excess risk for placental abruption, caesarean section, delivery induction, and post-delivery hemorrhage in women taking hypertensives. Infants were more often than expected born preterm, were small for gestational age, and had an excess of various neonatal symptoms. Cardiovascular defects occurred with an adjusted odds ratio of 2.59 (95% CI 1.92-3.51). The results were similar when the woman had used ACE inhibitors or other antihypertensives, notably beta blockers. Stillbirth rate was increased (risk ratio 1.87, 95% CI 1.02-3.02), again without any clear drug specificity.

    Conclusions There seems to be little drug specificity in the association between maternal use of antihypertensives and an increased risk for infant cardiovascular defects.

  • 50. Manger, Mari S.
    et al.
    Taneja, Sunita
    Strand, Tor A.
    Ueland, Per M.
    Refsum, Helga
    Schneede, Jörn
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Nygard, Ottar
    Sommerfelt, Halvor
    Bhandari, Nita
    Poor Folate Status Predicts Persistent Diarrhea in 6-to 30-Month-Old North Indian Children2011Inngår i: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 141, nr 12, 2226-2232 s.Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Poor micronutrient status is associated with diarrheal illness, but it is not known whether low folate and/or cobalamin status are independent risk factors for diarrhea. We measured the association between plasma folate and cobalamin and subsequent diarrheal morbidity in a prospective cohort study of 2296 children aged 6-30 mo in New Delhi, India. Plasma concentrations of folate, cobalamin, total homocysteine (tHcy), and methylmalonic acid were determined at baseline. Whether a child had diarrhea was recorded during weekly visits in a 4-mo zinc supplementation trial. Diarrhea episodes lasting <7, >= 7, and >= 14 d were classified as acute, prolonged, and persistent, respectively. There was a total of 4596 child periods with acute, 633 with prolonged, and 117 with persistent diarrhea during follow-up. Children with plasma folate concentrations in the lowest quartile had higher odds of persistent diarrhea than children in the other quartiles [adjusted OR = 1.77(95% CI = 1.14, 2.75); P = 0.01]. This effect differed between boys [adjusted OR = 2.51 (95% CI = 1.47, 4.28)] and girls [adjusted OR = 1.03 (95% CI = 0.53, 2.01); P-interaction = 0.030]. We found a small but significant association between high plasma tHcy concentration and acute diarrhea [adjusted OR = 1.14 (95% CI = 1.04, 1.24); P = 0.006]. Plasma cobalamin concentration was not a predictor of diarrheal morbidity. In conclusion, poor folate status was an independent predictor of persistent diarrhea in this population. J. Nutr. 141: 2226-2232, 2011.

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