| 1. |
- Yildiz, B, et al.
(author)
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Live well, die well - an international cohort study on experiences, concerns and preferences of patients in the last phase of life: the research protocol of the iLIVE study
- 2022
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In: BMJ OPEN. - : BMJ. - 2044-6055. ; 12:8
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Journal article (other academic/artistic)abstract
- Adequately addressing the needs of patients at the end of life and their relatives is pivotal in preventing unnecessary suffering and optimising their quality of life. The purpose of the iLIVE study is to contribute to high-quality personalised care at the end of life in different countries and cultures, by investigating the experiences, concerns, preferences and use of care of terminally ill patients and their families.Methods and analysisThe iLIVE study is an international cohort study in which patients with an estimated life expectancy of 6 months or less are followed up until they die. In total, 2200 patients will be included in 11 countries, that is, 200 per country. In addition, one relative per patient is invited to participate. All participants will be asked to fill in a questionnaire, at baseline and after 4 weeks. If a patient dies within 6 months of follow-up, the relative will be asked to fill in a post-bereavement questionnaire. Healthcare use in the last week of life will be evaluated as well; healthcare staff who attended the patient will be asked to fill in a brief questionnaire to evaluate the care that was provided. Qualitative interviews will be conducted with patients, relatives and healthcare professionals in all countries to gain more in-depth insights.Ethics and disseminationThe cohort study has been approved by ethics committees and the institutional review boards (IRBs) of participating institutes in all countries. Results will be disseminated through the project website, publications in scientific journals and at conferences. Within the project, there will be a working group focusing on enhancing the engagement of the community at large with the reality of death and dying.Trial registration numberNCT04271085.
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| 2. |
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| 3. |
- Gustafsdottir, S. S., et al.
(author)
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Making Europe health literate: including older adults in sparsely populated Arctic areas
- 2022
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In: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 22:1
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Journal article (peer-reviewed)abstract
- Background Older people have been identified as having lower health literacy (HL) than the general population average. Living in sparsely populated Arctic regions involves unique health challenges that may influence HL. The research aim was to explore the level of HL, its problematic dimensions, and its association with the selection of contextual factors among older adults living in sparsely populated areas in Northern Iceland. Method This was a cross-sectional study based on a stratified random sample from the national register of one urban town and two rural areas. The study included 175 participants (57.9% participation rate) who were community-dwelling (40% rural) and aged 65-92 years (M 74.2 +/- SD 6.3), 43% of whom were women. Data were collected in 2017-2018 via face-to-face interviews, which included the standardised European Health Literacy Survey Questionnaire-short version (HLS-EU-Q16) with a score range from 0 to 16 (low-high HL). Results The level of HL ranged from 6-16 (M 13.25, SD +/- 2.41) with 65% having sufficient HL (score 13-16), 31.3% problematic HL (score 9-12) and 3.7% inadequate HL (score 0-8). Most problematic dimension of HL was within the domains of disease prevention and health promotion related to information in the media. Univariate linear regression revealed that better HL was associated with more education (p=0.001), more resiliency (p=0.001), driving a car (p=0.006), good access to health care- (p=0.005) and medical service (p=0.027), younger age (p=0.005), adequate income (p=0.044) and less depression (p=0.006). Multivariable analysis showed that more education (p=0.014) and driving a car (p=0.017) were independent predictors of better HL. Conclusion Difficulties in HL concern information in the media. HL was strongly associated with education and driving a car however, not with urban-rural residency. Mobility and access should be considered for improving HL of older people.
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| 4. |
- Mikaelsdottir, E, et al.
(author)
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Genetic variants associated with platelet count are predictive of human disease and physiological markers
- 2021
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1, s. 1132-
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Journal article (peer-reviewed)abstract
- Platelets play an important role in hemostasis and other aspects of vascular biology. We conducted a meta-analysis of platelet count GWAS using data on 536,974 Europeans and identified 577 independent associations. To search for mechanisms through which these variants affect platelets, we applied cis-expression quantitative trait locus, DEPICT and IPA analyses and assessed genetic sharing between platelet count and various traits using polygenic risk scoring. We found genetic sharing between platelet count and counts of other blood cells (except red blood cells), in addition to several other quantitative traits, including markers of cardiovascular, liver and kidney functions, height, and weight. Platelet count polygenic risk score was predictive of myeloproliferative neoplasms, rheumatoid arthritis, ankylosing spondylitis, hypertension, and benign prostate hyperplasia. Taken together, these results advance understanding of diverse aspects of platelet biology and how they affect biological processes in health and disease.
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| 5. |
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| 6. |
- Sigurðardóttir, E. S., et al.
(author)
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Female sex hormones and symptoms of obstructive sleep apnea in European women of a population-based cohort
- 2022
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17
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Journal article (peer-reviewed)abstract
- Background The prevalence of obstructive sleep apnea is higher in women after menopause. This is suggested to be a result of an altered sex hormone balance but has so far not been confirmed in a population-based study. Objective To investigate whether serum concentration of estrogens and progesterone are associated with the prevalence of sleep apnea symptoms in middle-aged women of the general population. Methods We analyzed data from 774 women (40–67 years) from 15 study centers in seven countries participating in the second follow-up of the European Community Respiratory Health Survey (2010–2012). Multiple logistic regression models were fitted with self-reported symptoms of sleep apnea as outcomes and serum concentrations of various estrogens and progesterone as predictors. All analyses were adjusted for relevant covariates including age, BMI, education, study center, smoking habits, and reproductive age. Results Among all included women, a doubling of serum concentrations of estrone and progesterone was associated with 19% respectively 9% decreased odds of snoring. Among snorers, a doubling of the concentrations of 17β-estradiol, estrone and estrone 3-sulfate was associated with 18%, 23% and 17% decreased odds of breathing irregularly, and a doubling of the progesterone concentration was further associated with 12% decreased odds of waking up suddenly with a chocking sensation. Other evaluated associations were not statistically significant. Conclusions Middle-aged women with low serum estrogen and progesterone levels are more likely to snore and report symptoms of obstructive sleep apnea.
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| 7. |
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| 8. |
- Exarchou, S., et al.
(author)
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MORTALITY IN PATIENTS WITH PSORIATIC ARTHRITIS IN SWEDEN
- 2021
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In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80, s. 130-131
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Journal article (other academic/artistic)abstract
- In contrast to the increased mortality reported in other inflammatory diseases such as rheumatoid arthritis and psoriasis, prior mortality studies in psoriatic arthritis (PsA) have shown inconsistent results.Objectives:To compare all-cause mortality between PsA patients in Sweden and matched general population controls, and to describe cause of death distributions in the two groups.Methods:All individuals in Sweden with ≥1 main diagnosis of PsA (ICD-10: L40.5/M07.0-M07.3) from outpatient visits to rheumatology or internal medicine clinics at age ≥18 years (y) 2001-2017 were identified from the Swedish National Patient Register. Each case was matched to 5 general population controls based on sex, county and age in the year of the first registered arthritis diagnosis for the case. Cases and controls were followed from 1 Jan, 2007, or from first PsA diagnosis thereafter for index cases, until first occurrence of death (data from the Swedish Cause of Death Register), emigration or 31 Dec, 2018. Mortality was assessed overall, as well as stratified by sex (45% males) and disease duration (PsA diagnosis prior to 2007 [38% of cases] vs. 2007-2017), using matched Cox proportional hazard regression, or – in case the Cox assumption regarding proportionality did not hold – matched Breslow test. To account for potential PsA misclassification (in a previous validation study, 86% of 400 cases fulfilled PsA classification criteria), a sensitivity analysis was performed by randomly replacing 20% of cases with one of their own controls. Moreover, incidence rate ratios (IRR) of death were calculated overall and stratified by sex, disease duration and age. Finally, causes of death (from the Cause of Death Register) were described for PsA cases and controls.Results:Over the 12y follow-up, 3 121 deaths occurred among 33 036 PsA cases (268 402 person-years at risk) and 12 884 deaths among 161 144 controls (1 302 250 person-years), resulting in an increased mortality among the PsA cases (HR 1.11 [95%CI 1.07-1.16], p<0.001, Figure and Table; sensitivity analysis HR 1.09 [1.05-1.14]). The increased mortality was seen mainly among female PsA cases and among cases with longer disease duration (Figure; Table). IRR:s of death were significantly increased for all ages except <40y, with the numerically highest point-estimates for ages 40-49y and 50-59y (Table). Cause of death frequencies among the PsA cases/controls: cardiovascular disease 29/27%; diabetes mellitus 2.1/2.5%; chronic kidney disease 0.4/0.3%; infection 5.7/4.5%; chronic pulmonary disease 5.1/4.1%; malignancy 29/34%; suicide 2.3/2.0%; other 27/26%.Table 1.Mortality rates and incidence rate ratiosPsA casesPopulation controlsNumber of deathsPerson-yearsat riskMortality rate*Number of deathsPerson-yearsat riskMortality rate*Incidence rate ratio (95%CI)Overall3 121268 40211.612 8841 302 2509.91.18 (1.13-1.22)Males1 459120 51712.16 468580 28511.11.09 (1.03-1.15)Females1 662147 88611.26 416721 9668.91.27 (1.20-1.34)Longer disease duration1 943139 37913.97 459670 17411.11.25 (1.19-1.32)Shorter disease duration1 178129 0239.15 425632 0778.61.06 (1.00-1.13)Age intervals (years)<401833 5680.598163 2780.60.89 (0.54-1.48)40-499050 5521.8322246 9551.31.37 (1.08-1.73)50-5928065 8204.31 131321 7303.51.21 (1.06-1.38)60-6972370 22410.33 132341 5879.21.12 (1.04-1.22)70-7996037 23225.84 160178 90923.31.11 (1.03-1.19)≥801 05011 00795.44 04149 79181.21.18 (1.10-1.26)* Per 1000 person-years.Conclusion:In this nationwide 12y assessment, the mortality risk among PsA patients in Sweden was increased by around 10% as compared to the general population, mainly driven by increased risks among females and patients with longer disease duration. Cause of death distributions were numerically similar between PsA cases and controls.References:Disclosure of Interests:Sofia Exarchou Consultant of: AbbVie, Novartis, Daniela Di Giuseppe: None declared, Gerd-Marie Alenius: None declared, Eva Klingberg Speakers bureau: Eli Lilly, Consultant of: Novartis, Grant/research support from: Roche, Valgerdur Sigurdardottir Consultant of: Novartis, Sanofi, Sara Wedrén: None declared, Ulf Lindström: None declared, Carl Turesson Speakers bureau: AbbVie, BMS, Pfizer, Roche, Consultant of: Roche, Grant/research support from: BMS, Lennart T.H. Jacobsson Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Johan Askling Grant/research support from: For ARTIS: AbbVie, BMS, Eli Lilly, Merck, Pfizer, Roche, Samsung Bioepis, Sanofi, UCB. This study was supported by AbbVie, Amgen, Eli Lilly, Novartis and Pfizer. The sponsors were allowed to comment on the study protocol and were provided with a report of the results, but had no influence on the study design or decision to submit the abstract., Johan K Wallman Consultant of: Celgene, Eli Lilly, Novartis
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Skuladottir, AT, et al.
(author)
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A genome-wide meta-analysis uncovers six sequence variants conferring risk of vertigo
- 2021
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1, s. 1148-
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Journal article (peer-reviewed)abstract
- Vertigo is the leading symptom of vestibular disorders and a major risk factor for falls. In a genome-wide association study of vertigo (Ncases = 48,072, Ncontrols = 894,541), we uncovered an association with six common sequence variants in individuals of European ancestry, including missense variants in ZNF91, OTOG, OTOGL, and TECTA, and a cis-eQTL for ARMC9. The association of variants in ZNF91, OTOGL, and OTOP1 was driven by an association with benign paroxysmal positional vertigo. Using previous reports of sequence variants associating with age-related hearing impairment and motion sickness, we found eight additional variants that associate with vertigo. Although disorders of the auditory and the vestibular system may co-occur, none of the six genome-wide significant vertigo variants were associated with hearing loss and only one was associated with age-related hearing impairment. Our results uncovered sequence variants associating with vertigo in a genome-wide association study and implicated genes with known roles in inner ear development, maintenance, and disease.
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| 13. |
- Vesteinsdottir, I., et al.
(author)
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Risk factors for Clostridium difficile toxin-positive diarrhea: a population-based prospective case-control study
- 2012
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In: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 1435-4373 .- 0934-9723. ; 31:10, s. 2601-2610
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Journal article (peer-reviewed)abstract
- Increased incidence and severity of Clostridium difficile infections (CDIs) is of major concern. However, by minimizing known risk factors, the incidence can be decreased. The aim of this investigation was to calculate the incidence and assess risk factors for CDI in our population. A 1-year prospective population-based nationwide study in Iceland of CDIs was carried out. For risk factor evaluation, each case was matched with two age- and sex-matched controls that tested negative for C. difficile toxin. A total of 128 CDIs were identified. The crude incidence was 54 cases annually per 100,000 population > 18 years of age. Incidence increased exponentially with older age (319 per 100,000 population > 86 years of age). Community-acquired origin was 27 %. Independent risk factors included: dicloxacillin (odds ratio [OR]: 7.55, 95 % confidence interval [CI]: 1.89-30.1), clindamycin (OR: 6.09, 95 % CI: 2.23-16.61), ceftriaxone (OR: 4.28, 95 % CI: 1.59-11.49), living in a retirement home (OR: 3.9, 95 % CI: 1.69-9.16), recent hospital stay (OR: 2.3, 95 % CI: 1.37-3.87). Proton pump inhibitors (PPIs) were used by 60/111 (54 %) versus 91/222 (41 %) (p = 0.026) and ciprofloxacin 19/111 (17 %) versus 19/222 (9 %) (p = 0.027) for cases and controls, respectively. In all, 75 % of primary CDIs treated with metronidazole recovered from one course of treatment. CDI was mostly found among elderly patients. The most commonly identified risk factors were broad-spectrum antibiotics and recent contact with health care institutions. PPI use was significantly more prevalent among CDI patients.
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| 14. |
- Wallman, J. K., et al.
(author)
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High degree of classification criteria fulfillment among patients with clinical psoriatic arthritis diagnoses in Sweden
- 2020
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In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 79, s. 1725-1726
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Journal article (other academic/artistic)abstract
- The clinical diagnosis of psoriatic arthritis (PsA) may be challenging. In Sweden, the vast majority of PsA cases are diagnosed within rheumatology or internal medicine (IM). Knowledge of the correspondence between clinical ICD diagnoses and classification criteria fulfillment is crucial to interpret studies identifying cases based on ICD codes.Objectives:To assess the degree to which patients with clinical PsA diagnoses in Sweden fulfill established PsA classification criteria.Methods:Four hundred patients with ≥1 outpatient physician visit to one of five rheumatology or IM departments (3 university/2 county departments, spread across Sweden) 2013-2015 with a main ICD-10 diagnosis of PsA (L40.5/M07.0-M07.3), were randomly selected from the Swedish National Patient Register (80 cases/site). Based on a structured medical record review, positive predictive values (PPV) of a clinical PsA diagnosis (i.e. ≥1 visit with a PsA ICD-10 code) for fulfillment of the following classification criteria were assessed: CASPAR,[1] Moll & Wright,[2] Vasey & Espinoza,[3] and Modified ESSG criteria for PsA,[4] respectively (as well as for any of these); ASAS criteria for peripheral or axial spondyloarthritis (SpA) [5]; and the 1987 ACR criteria for rheumatoid arthritis (RA).[6] Subanalyses regarding CASPAR fulfillment were also performed restricted to patients with available rheumatoid factor and peripheral X-ray status (central CASPAR items; n=227), and among patients with ≥2 ICD codes for PsA, of which ≥1 from a rheumatology/IM department (n=353).Results:Out of 400 clinically diagnosed PsA patients, 343 (86%) fulfilled any of the 4 PsA classification criteria, with a PPV for CASPAR fulfillment of 69% (rising to 73-82% in the subanalyses;Figure 1). Substantial overlap was seen regarding fulfillment of the 4 PsA criteria (Figure 2A). Moreover, 86% fulfilled the ASAS peripheral or axial SpA criteria, while the 1987 ACR definition of RA was met by 27% – in both cases with the great majority also classifiable as PsA (Figure 2B). Most patients not fulfilling any PsA criteria had either no verified arthritis or polyarticular disease (Table). Overall, only 6.5% of the clinical PsA diagnoses were judged as clearly wrong by the rheumatologists performing the medical record assessments.Conclusion:The validity of clinical ICD-10 diagnoses for PsA in the Swedish National Patient Register is good, with a PPV of 86% for the fulfillment of established PsA classification criteria.References:[1]Arthritis Rheum2006;54:2665-73[2]Semin Arthritis Rheum 1973;3:55-78[3]In: Calin A, editor. Spondyloarthropathies. Orlando: Grune & Stratton; 1984:151-85[4]Ann Rheum Dis2005;64(Suppl II):ii3–ii8[5]Ann Rheum Dis2011;70:25-31[6]Arthritis Rheum1988;31:315-24Patient characteristics (n=400), stratified by classification criteria fulfillmentFulfilling anyPsA criterian=343Not fulfilling anyPsA criterian=57Male sex, %4644Age, yrs; mean (SD)59 (14)62 (15)Symptom duration, yrs; mean (SD)18 (12)16 (13)Psoriasis, %8947Nail psoriasis, %3811Arthritis, %9358 Monoarthritis, %*7.90 Oligoarthritis, %*4522 Polyarthritis, %*4778DIP-joint arthritis, %287.0Dactylitis, %281.8Enthesitis, %4219Inflammatory back pain, %275.3RF positive, %5.814ACPA positive, %4.43.5Arthritic X-ray changes in hands/feet, %3321* % of patients with arthritis of known distribution. Missing data: 0-4%, except forRF (33%), ACPA (37%) and X-ray changes (20%).Acknowledgments:This work was supported by Celgene, Novartis, Pfizer, Reumatikerförbundet and Psoriasisförbundet.Disclosure of Interests:Johan K Wallman Consultant of: AbbVie, Celgene, Eli Lilly, Novartis and UCB Pharma, Gerd-Marie Alenius: None declared, Eva Klingberg Grant/research support from: Roche, Consultant of: Novartis, Speakers bureau: Eli Lilly, Valgerdur Sigurdardottir Consultant of: Novartis, Sara Wedrén: None declared, Sofia Exarchou: None declared, Ulf Lindström: None declared, Daniela Di Giuseppe: None declared, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma, Lennart T.H. Jacobsson Consultant of: AbbVie, Eli Lilly, Janssen, Novartis and Pfizer
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| 15. |
- Wallman, J. K., et al.
(author)
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Validity of clinical psoriatic arthritis diagnoses made by rheumatologists in the Swedish National Patient Register
- 2023
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In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 52:4, s. 374-384
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Journal article (peer-reviewed)abstract
- Objectives : Knowledge of the correspondence between clinical ICD diagnoses and classification criteria fulfilment is crucial to interpret studies identifying cases via ICD codes. We assessed the degree to which patients registered with ICD-10 diagnoses of psoriatic arthritis (PsA) in the Swedish National Patient Register (NPR) fulfil established PsA classification criteria. Method Four hundred patients with at least one outpatient visit to one of five rheumatology or internal medicine departments (three university/two county departments across Sweden) in 2013-2015, with a main ICD-10 diagnosis of PsA (L40.5-M07.3), were randomly selected (80 cases/site). Through a structured medical record review, positive predictive values (PPVs) for fulfilment of the following classification criteria were assessed: CASPAR, Moll and Wright, Vasey and Espinoza, and modified ESSG criteria for PsA. A subset analysis regarding CASPAR fulfilment was also performed among cases with available rheumatoid factor and peripheral X-ray status (central CASPAR items; n = 227). Results Of the 400 patients with a main ICD-10 diagnosis of PsA, 343 (86%) fulfilled at least one of the four PsA classification criteria. PPVs for the different criteria were: CASPAR 69% (82% in the subset analysis), Moll and Wright 51%, Vasey and Espinoza 76%, and modified ESSG 64%. Overall, only 6.5% of the 400 PsA diagnoses were judged as clearly incorrect by the medical record reviewers. Conclusion The validity of rheumatologist-made, clinical ICD-10 diagnoses for PsA in the Swedish NPR is good, with PPVs of 69-82% for CASPAR fulfilment and 86% for meeting any established PsA classification criteria.
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| 16. |
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| 17. |
- Andreassen, A. K., et al.
(author)
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Everolimus Initiation and Early Calcineurin Inhibitor Withdrawal in Heart Transplant Recipients: A Randomized Trial
- 2014
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In: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 14:8, s. 1828-1838
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Journal article (peer-reviewed)abstract
- In a randomized, open-label trial, everolimus was compared to cyclosporine in 115 de novo heart transplant recipients. Patients were assigned within 5 days posttransplant to low-exposure everolimus (3-6 ng/mL) with reduced-exposure cyclosporine (n 56), or standard-exposure cyclosporine (n = 59), with both mycophenolate mofetil and corticosteroids. In the everolimus group, cyclosporine was withdrawn after 7-11 weeks and everolimus exposure increased (6-10 ng/mL). The primary efficacy end point, measured GFR at 12 months posttransplant, was significantly higher with everolimus versus cyclosporine (mean +/- SD: 79.8 +/- 17.7 mL/min/1.73m 2 vs. 61.5 +/- 19.6 mL/min/1.73m 2; p<0.001). Coronary intravascular ultrasound showed that the mean increase in maximal intimal thickness was smaller (0.03 mm [95% CI 0.01, 0.05 mm] vs. 0.08 mm [95% CI 0.05, 0.12 mm], p = 0.03), and the incidence of cardiac allograft vasculopathy (CAV) was lower (50.0% vs. 64.6%, p = 0.003), with everolimus versus cyclosporine at month 12. Biopsy-proven acute rejection after weeks 7-11 was more frequent with everolimus (p = 0.03). Left ventricular function was not inferior with everolimus versus cyclosporine. Cytomegalovirus infection was less common with everolimus (5.4% vs. 30.5%, p<0.001); the incidence of bacterial infection was similar. In conclusion, everolimus-based immunosuppression with early elimination of cyclosporine markedly improved renal function after heart transplantation. Since postoperative safety was not jeopardized and development of CAV was attenuated, this strategy may benefit long-term outcome.
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| 18. |
- Arora, S., et al.
(author)
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The Effect of Everolimus Initiation and Calcineurin Inhibitor Elimination on Cardiac Allograft Vasculopathy in De Novo Recipients: One-Year Results of a Scandinavian Randomized Trial
- 2015
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In: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 15:7, s. 1967-1975
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Journal article (peer-reviewed)abstract
- Early initiation of everolimus with calcineurin inhibitor therapy has been shown to reduce the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant recipients. The effect of de novo everolimus therapy and early total elimination of calcineurin inhibitor therapy has, however, not been investigated and is relevant given the morbidity and lack of efficacy of current protocols in preventing CAV. This 12-month multicenter Scandinavian trial randomized 115 de novo heart transplant recipients to everolimus with complete calcineurin inhibitor elimination 7-11 weeks after HTx or standard cyclosporine immunosuppression. Ninety-five (83%) patients had matched intravascular ultrasound examinations at baseline and 12 months. Mean (SD) recipient age was 49.9 +/- 13.1 years. The everolimus group (n=47) demonstrated significantly reduced CAV progression as compared to the calcineurin inhibitor group (n=48) (Maximal Intimal Thickness 0.03 +/- 0.06 and 0.08 +/- 0.12mm, Percent Atheroma Volume 1.3 +/- 2.3 and 4.2 +/- 5.0%, Total Atheroma Volume 1.1 +/- 19.2mm(3) and 13.8 +/- 28.0mm(3) [all p-values0.01]). Everolimus patients also had a significantly greater decline in levels of soluble tumor necrosis factor receptor-1 as compared to the calcineurin inhibitor group (p=0.02). These preliminary results suggest that an everolimus-based CNI-free can potentially be considered in suitable de novo HTx recipients.
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| 19. |
- Arora, Satish, et al.
(author)
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Virtual Histology Assessment of Cardiac Allograft Vasculopathy Following Introduction of Everolimus—Results of a Multicenter Trial
- 2012
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In: American Journal of Transplantation. - : Wiley-Blackwell. - 1600-6135 .- 1600-6143. ; 12:10, s. 2700-2709
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Journal article (peer-reviewed)abstract
- In this 12-month multicenter Scandinavian study, 78 maintenance heart transplant (HTx) recipients randomized to everolimus with reduced calcineurin inhibitor (CNI) exposure or continued standard CNI-therapy underwent matched virtual histology (VH) examination to evaluate morphological progression of cardiac allograft vasculopathy (CAV). Parallel measurement of a range of inflammatory markers was also performed. A similar rate of quantitative CAV progression was observed in the everolimus (n = 30) and standard CNI group (n = 48) (plaque index 1.9 +/- 3.8% and 1.6 +/- 3.9%, respectively; p = 0.65). However, VH analysis revealed a significant increase in calcified (2.4 +/- 4.0 vs. 0.3 +/- 3.1%; p = 0.02) and necrotic component (6.5 +/- 8.5 vs. 1.1 +/- 8.6%; p = 0.01) among everolimus patients compared to controls. The increase in necrotic and calcified components was most prominent in everolimus patients with time since HTx andgt;5.1 years and was accompanied by a significant increase in levels of von Willebrand (vWF) factor (p = 0.04) and vascular cell adhesion molecule (VCAM) (p = 0.03). Conversion to everolimus and reduced CNI is associated with a significant increase in calcified and necrotic intimal components and is more prominent in patients with a longer time since HTx. A significant increase in vWF and VCAM accompanied these qualitative changes and the prognostic implication of these findings requires further investigation.
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| 20. |
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| 21. |
- Dagsson-Waldhauserova, P., et al.
(author)
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Physical properties of suspended dust during moist and low wind conditions in Iceland
- 2014
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In: Icelandic Agricultural Sciences. - 1670-567X. ; 27, s. 25-39
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Journal article (peer-reviewed)abstract
- We measured a dust event which occurred during wet and low wind/windless conditions as the result of surface heating in August 2013. Maximum particle number concentration (PM similar to 0.3-10 mu m) reached 149,954 particles cm(-3) min(-1) while mass concentration (PM<10 m) was 1757 g m-3 min-1. The suspended dust was very fine with the highest number of particles in the size range 0.3-0.337 mu m, followed by particles 1.5-5 mu m in diameter. Close-to-ultrafine particle size distributions showed a significant increase in number with the severity of the measured dust event (during dust peaks). Number concentrations were well correlated with mass concentrations. The mineralogy and geochemical compositions showed that glaciogenic dust contains sharp-tipped shards with bubbles and 80 % of the particulate matter is volcanic glass rich in heavy metals. Wet dust particles were mobilized within < 4 hours. This is the first scientific study of particle size distributions in an Icelandic dust event including findings on initiation of dust suspension.
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| 22. |
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| 23. |
- Exarchou, Sofia, et al.
(author)
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The National Prevalence of Clinically Diagnosed Psoriatic Arthritis in Sweden in 2017
- 2023
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In: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 50:6, s. 781-788
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Journal article (peer-reviewed)abstract
- Objective. Psoriatic arthritis (PsA) prevalence estimates vary across studies; studies based on national data are few. We aimed to estimate the prevalence of clinically diagnosed PsA in Sweden in 2017, overall and stratified by sex, age, education, and geography, and to quantify disease-modifying antirheumatic drug (DMARD) use among those in contact with specialized rheumatology care between 2015 and 2017.Methods. Individuals who were 18 to 79 years of age, alive and residing in Sweden on December 31, 2017, and had a prior PsA diagnosis were identified from the National Patient Register (NPR) and/or the Swedish Rheumatology Quality Register (SRQ). PsA prevalence was estimated according to a base case (BC) defini-tion (ie, & GE; 1 main PsA International Classification of Diseases code from rheumatology or internal medicine departments in the NPR or a PsA diagnosis in the SRQ), according to 4 sensitivity analysis definitions, and for those seen in specialized rheumatology care between 2015 and 2017. In the latter group, DMARD use during 2017 was also assessed. Data for stratifications were retrieved from national registers.Results. The crude national prevalence of PsA for adults, aged 18 to 79 years, was estimated at 0.39%, according to the BC definition; 0.34% after accounting for diagnostic misclassification; and 0.32% to 0.50% across all sensitivity analyses. The prevalence was lower in males and in those with a higher level of education. The prevalence for those seen in specialized rheumatology care between 2015 and 2017 was estimated at 0.24%. During 2017, 32% of patients in this population received biologic or targeted synthetic DMARDs, and 41% received conventional synthetic DMARDs only.Conclusion. The prevalence of clinically diagnosed PsA in adults, aged 18 to 79 years, in Sweden in 2017 was around 0.35%. Among PsA cases in recent contact with specialized rheumatology care, almost three-fourths received DMARD therapy in 2017.
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| 24. |
- Graflund, M., et al.
(author)
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HPV-DNA, vascular space invasion, and their impact on the clinical outcome in early-stage cervical carcinomas
- 2014
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In: International Journal of Gynecological Cancer. - Malden, USA : Blackwell Publishing. - 1048-891X .- 1525-1438. ; 14:5, s. 896-902
-
Journal article (peer-reviewed)abstract
- The present study was designed to analyze the relationship of human papillomavirus (HPV)-DNA, microvessel density, and their impact on clinical outcome in early cervical carcinoma. HPV-DNA was evaluated in 171 cases of cervical carcinoma treated from 1965 to 1990. In 110 cases, the analyses could be performed. A polymerase chain reaction technique was used on paraffin-embedded specimens obtained before the start of therapy. HPV-DNA of any type was detected in 78% (86/110) of all evaluable tumors. HPV16 was the predominant type and was detected in 56% (62/110), HPV18 in 8% (9/110), and HPV35 in 21% (23/110). Patients with tumors containing HPV16 or HPV18 were significantly (P = 0.011) younger than patients with tumors not containing either of these two subtypes. Vascular space invasion and lymph node metastases were observed more frequently in tumors expressing HPV16 and HPV18 (P = 0.002, P = 0.047) than in tumors negative for these HPV strains. Tumors containing HPV16 and HPV18 were significantly (P = 0.012) larger and more frequently (P = 0.005) associated with higher FIGO stages. The cancer-specific survival rate was lower for patients with HPV16- and HPV18-positive tumors, but the difference was not statistically significant. The microvessel density was a non-significant prognostic factor. The overall 5-year survival rate of the complete series was 91%. It was concluded that HPV-DNA was a prognostic factor in early-stage cervical cancer and was associated with the age of the patient, vascular space invasion, lymph node metastases, tumor size, and FIGO stage.
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| 25. |
- Graflund, M., et al.
(author)
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Relation between HPV-DNA and expression of p53, bcl-2, p21WAF-1, MIB-1, HER-2/neu and DNA ploidy in early cervical carcinoma : correlation with clinical outcome
- 2004
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In: Oncology Reports. - Athens, Greece : Spandidos Publications. - 1021-335X .- 1791-2431. ; 12:1, s. 169-176
-
Journal article (peer-reviewed)abstract
- The purpose of the present study was to analyze the relation between the expression of p53, bcl-2, p21WAF1, MIB-1, HER-2/neu, DNA ploidy and HPV16 or 18 infections with clinical parameters. HPV-DNA was evaluated in 171 early cervical carcinomas treated from 1965 to 1990 and detected by PCR (polymerase chain reaction) on paraffin specimens obtained before therapy was started. HPV-DNA of any type was detected in 78% (86/110) of all tumors, HPV16 was the predominant type and was seen in 56% (62/110), HPV18 in 8% (9/110) and HPV35 in 21% (23/110). Patients with HPV16 or 18 were significantly (P=0.011) younger than patients with tumors not containing these two HPV subtypes. Lymph node metastases were seen more frequently (P=0.047) in tumors expressing HPV16 or 18. Tumor size was associated with the HPV-type. The frequency of DNA aneuploidy was lower in high-risk HPV tumors than in tumors with other HPV subtypes (P=0.014). MIB-1 expression was highly significantly (P=0.00007) associated with presence of HPV16 or 18. The cancer-specific survival rate was lower for patients with HPV16 and 18 positive tumors, but the difference was not statistically significant. The overall 5-year survival rate of the complete series was 91%. In conclusion, the HPV DNA subtype was a prognostic factor in early stage cervical cancer and it was associated with age, positive lymph nodes, tumor size, DNA ploidy and the proliferation marker MIB-1.
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| 26. |
- Hautakangas, H, et al.
(author)
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Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
- 2022
-
In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:2, s. 152-
-
Journal article (peer-reviewed)abstract
- Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.
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| 27. |
- Jenset, Inga S, et al.
(author)
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The benefits of using videos for developing teachers’ professional vision
- 2024. - 1
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In: Using video to foster teacher development. - : Routledge. - 9781032547688 - 9781003427414 ; , s. 17-32
-
Book chapter (other academic/artistic)abstract
- The use of video is steadily highlighted as a powerful tool for teachers’ professional learning. The research literature points to a range of different advantages and purposes for using video, and this chapter summarizes research specifically indicating that the use of videos can contribute to developing in-service and pre-service teachers’ professional vision. The chapter shows how the use of video can enable a variety of perspectives on teaching, for instance by focused attention on the students’ perspective. The chapter also outlines research indicating how the use of video can enhance teacher noticing and reflective skills, and finally discusses how video can contribute to an inquiry stance necessary to develop teaching. Throughout the chapter, empirical data is shared to illustrate how teachers pre- and in-service teachers themselves experience using video as a professional tool-and how that has impacted their own professional learning. © 2024 selection and editorial matter, Marte Blikstad-Balas and Inga Staal Jenset; individual chapters, the contributors.
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| 28. |
- Johansson, Inger, 1953, et al.
(author)
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Cytomegalovirus infection and disease reduce 10-year cardiac allograft vasculopathy-free survival in heart transplant recipients
- 2015
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In: Bmc Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 15
-
Journal article (peer-reviewed)abstract
- Background: Cytomegalovirus (CMV) is associated with an increased risk of cardiac allograft vasculopathy (CAV), the major limiting factor for long-term survival after heart transplantation (HTx). The purpose of this study was to evaluate the impact of CMV infection during long-term follow-up after HTx. Methods: A retrospective, single-centre study analyzed 226 HTx recipients (mean age 45 +/- 13 years, 78 % men) who underwent transplantation between January 1988 and December 2000. The incidence and risk factors for CMV infection during the first year after transplantation were studied. Risk factors for CAV were included in an analyses of CAV-free survival within 10 years post-transplant. The effect of CMV infection on the grade of CAV was analyzed. Results: Survival to 10 years post-transplant was higher in patients with no CMV infection (69 %) compared with patients with CMV disease (55 %; p = 0.018) or asymptomatic CMV infection (54 %; p = 0.053). CAV-free survival time was higher in patients with no CMV infection (6.7 years; 95 % CI, 6.0-7.4) compared with CMV disease (4.2 years; CI, 3.2-5.2; p < 0.001) or asymptomatic CMV infection (5.4 years; CI, 4.3-6.4; p = 0.013). In univariate analysis, recipient age, donor age, coronary artery disease (CAD), asymptomatic CMV infection and CMV disease were significantly associated with CAV-free survival. In multivariate regression analysis, CMV disease, asymptomatic CMV infection, CAD and donor age remained independent predictors of CAV-free survival at 10 years post-transplant. Conclusions: CAV-free survival was significantly reduced in patients with CMV disease and asymptomatic CMV infection compared to patients without CMV infection. These findings highlight the importance of close monitoring of CMV viral load and appropriate therapeutic strategies for preventing asymptomatic CMV infection.
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| 29. |
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| 30. |
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| 31. |
- Lindström, Ulf, et al.
(author)
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Validity of ankylosing spondylitis and spondyloarthritis diagnoses in the Swedish National Patient Register
- 2014
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In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 32:5, s. 802-802
-
Journal article (other academic/artistic)abstract
- Background: Epidemiological studies of spondyloarthritis (SpA) are scarce. Using ICD-codes from the Swedish National Patient Register (NPR) offers unique possibilities for such studies. For this purpose, the validity of these ICD-codes needs to be determined.Objectives: To validate the ICD-codes for ankylosing spondylitis (AS) and SpA in the NPR against established classification criteria (modified New York (mNY), ASAS, Amor and ESSG criteria).Methods: All patients with an ICD-code of AS or SpA in the NPR 1966-2009 at a visit to a specialist in rheumatology or internal medicine, or corresponding hospitalization, were identified (n=20074). Following a structured procedure to achieve geographical representativeness, 500 random patients with a registered diagnosis of AS or SpA in 2007-2009 were selected. A structured review of clinical records, with extraction of necessary information for the established classification criteria was performed and positive predictive values (PPV) were calculated.Results: In this cohort 11472 (34% women) patients had received an AS diagnosis and 11004 (56% women) a SpA diagnosis. The overlap group having received both types of diagnoses had similar frequencies for fulfillment of mNY criteria, symptoms and signs of back disease as the group having been coded as AS only.Of those being coded as AS only, the PPV for fulfilling the mNY, any criteria set and any of the included criteria elements were 70%, 89% and 96% respectively.Of those with SpA (without AS ever) the corresponding PPV values were 20%, 79% and 99% respectively.Conclusions: A diagnosis of AS or SpA (without AS) had a high validity, suggesting that case identification based on ICD-codes in the Swedish NPR can be used for epidemiological studies of these diseases.
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| 32. |
- Lindström, Ulf, et al.
(author)
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Validity of ankylosing spondylitis and undifferentiated spondyloarthritis diagnoses in the Swedish National Patient Register
- 2015
-
In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 44:5, s. 369-376
-
Journal article (peer-reviewed)abstract
- Objectives: Epidemiological studies of spondyloarthritis (SpA), using ICD codes from the Swedish National Patient Register (NPR), offer unique possibilities but hinge upon an understanding of the validity of the codes. The aim of this study was to validate the ICD codes for ankylosing spondylitis (AS) and undifferentiated SpA (uSpA) in the NPR against the established classification criteria [modified New York (mNY), Assessment of SpondyloArthritis international Society (ASAS), Amor, and European Spondyloarthropathy Study Group (ESSG) criteria].Method: All patients with an ICD-8/9/10 code of AS or uSpA in the NPR 1966-2009 at a visit to a specialist in rheumatology or internal medicine or corresponding hospitalization, alive and living in Sweden 2009, were identified (n = 20 089). Following a structured procedure to achieve geographical representativeness, 500 random patients with a diagnosis of AS or uSpA in 2007-2009 were selected. Based on a structured review of clinical records, positive predictive values (PPVs) for fulfilling the criteria sets were calculated.Results: For those having received an ICD code for AS, the PPVs for fulfilling the mNY criteria or any set of SpA criteria were 70% and 89%, respectively. For those with an uSpA diagnosis (and never an AS diagnosis), the corresponding PPVs were 20% and 79%. The subset with both AS and uSpA diagnoses (overlap = 12%) were as likely to fulfil the mNY criteria as the group that had been coded as AS only.Conclusions: The diagnosis codes for AS or uSpA had high PPVs, suggesting that our case identification in the Swedish NPR can be used for nationwide, population-based, epidemiological studies of these diseases. © 2015 © 2015 Informa Healthcare on license from Scandinavian Rheumatology Research Foundation.
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| 33. |
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| 34. |
- Norup, A., et al.
(author)
-
Education, training, and practice among nordic neuropsychologists : Results from a professional practices survey
- 2017
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In: Clinical Neuropsychologist (Neuropsychology, Development and Cognition. - : Taylor & Francis. - 1385-4046 .- 1744-4144. ; 31:Supplement 1, s. 20-41
-
Journal article (peer-reviewed)abstract
- Objective: To investigate sociodemographic characteristics, clinical and academic training, work setting and salary, clinical activities, and salary and job satisfaction among practicing neuropsychologists in four Nordic countries. Methods: 890 neuropsychologists from Denmark, Finland, Norway, and Sweden participated in an internet-based survey between December 2013 and June 2015. Results: Three-fourths (76%) of the participants were women, with a mean age of 47years (range 24-79). In the total sample, 11% earned a PhD and 42% were approved as specialists in neuropsychology (equivalent to board certification in the U.S.). Approximately 72% worked full-time, and only 1% were unemployed. Of the participants, 66% worked in a hospital setting, and 93% had conducted neuropsychological assessments during the last year. Attention deficit hyperactivity disorder, learning disability, and intellectual disability were the most common conditions seen by neuropsychologists. A mean income of 53,277 Euros was found. Neuropsychologists expressed greater job satisfaction than income satisfaction. Significant differences were found between the Nordic countries. Finnish neuropsychologists were younger and worked more hours every week. Fewer Swedish neuropsychologists had obtained specialist approval and fewer worked full-time in neuropsychology positions. Danish and Norwegian neuropsychologists earned more money than their Nordic colleagues. Conclusion: This is the first professional practice survey of Nordic neuropsychologists to provide information about sociodemographic characteristics and work setting factors. Despite the well-established guidelines for academic and clinical education, there are relevant differences between the Nordic countries. The results of the study offer guidance for refining the development of organized and highly functioning neuropsychological specialty practices in Nordic countries.
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Sigurdardottir, Lara G., et al.
(author)
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Circadian disruption, sleep loss, and prostate cancer risk : a systematic review of epidemiologic studies
- 2012
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In: Cancer Epidemiology, Biomarkers and Prevention. - Philadelphia, USA : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:7, s. 1002-1011
-
Research review (peer-reviewed)abstract
- Disruption of the circadian system has been hypothesized to increase cancer risk, either because of direct disruption of the molecular machinery generating circadian rhythms or because of disruption of parameters controlled by the clock such as melatonin levels or sleep duration. This hypothesis has been studied in hormone-dependent cancers among women, but data are sparse about potential effects of circadian disruption on the risk of prostate cancer. This review systematically examines available data evaluating the effects of light at night, sleep patterns, and night shift work on prostate cancer risk.
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| 39. |
- Sigurdardottir, Lara G., et al.
(author)
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Urinary melatonin levels, sleep disruption, and risk of prostate cancer in elderly men
- 2015
-
In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 67:2, s. 191-194
-
Journal article (peer-reviewed)abstract
- Melatonin has anticarcinogenic properties in experimental models. We undertook a case-cohort study of 928 Icelandic men without prostate cancer (PCa) nested within the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort to investigate the prospective association between first morning-void urinary 6-sulfatoxymelatonin (aMT6s) levels and the subsequent risk for PCa, under the hypothesis that men with lower aMT6s levels have an increased risk for advanced PCa. We used weighted Cox proportional hazards models to assess the association between first morning-void aMT6s levels and PCa risk, adjusting for potential confounders. A total of 111 men were diagnosed with incident PCa, including 24 with advanced disease. Men who reported sleep problems at baseline had lower morning aMT6s levels compared with those who reported no sleep problems. Men with morning aMT6s levels below the median had a fourfold statistically significant increased risk for advanced disease compared with men with levels above the median (hazard ratio: 4.04; 95% confidence interval, 1.26-12.98). These results require replication in larger prospective studies with longer follow-up.Patient summary: In this report, we evaluated the prospective association between urinary aMT6s levels and risk of PCa in an Icelandic population. We found that lower levels of aMT6s were associated with an increased risk for advanced PCa.
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| 40. |
- Skulason, Bragi, et al.
(author)
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Assessing survival in widowers, and controls : a nationwide, six- to nine-year follow-up
- 2012
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In: BMC Public Health. - Stockholm : Karolinska Institutet, Dept of Public Health Sciences. - 1471-2458.
-
Journal article (peer-reviewed)abstract
- Background: The aim of this study was to assess if widowers had an increased mortality rate during the first 6 to 9 years after the death of their wife, compared initially to an age-matched control group and also compared to the general population of Iceland. Methods: The study base was comprised of all 371 men born in 1924-1969 who were widowed in Iceland in 1999-2001 and 357 controls, married men, who were matched by age and residence. The widowers and controls were followed through the years 2002-2007 using information from Statistics Iceland. Mortality rates were compared between the groups and also with the general population. The mortality rate comparisons were: study group vs. control group, on the one hand, and study group vs. general population on the other. Causes of death were also compared between widowers and their wives. Results: A statistically significant increase in mortality in the widowers’ group, compared to controls, was observed. Lifestyle-related factors could not be excluded as contributing to cause of death in these cases. Conclusions: Being a widower was related to an increased risk of death for at least 9 years after the death of their wife.
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| 41. |
- Svanborg, Per, 1978, et al.
(author)
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Shear bond strength of the ceramic veneer to additively manufactured titanium
- 2024
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In: Clinical and Experimental Dental Research. - 2057-4347. ; 10:1
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Journal article (peer-reviewed)abstract
- Objectives: The objective of this in vitro study was to evaluate the shear bond strength between the ceramic veneer and additively manufactured titanium with different surface treatments, and to compare with milled titanium. Also, to characterize the surface and the presence of an α-case layer of additively manufactured and milled titanium. Material and Methods: Sixty additively manufactured titanium grade 23, and 20 milled titanium grade 4 cylindrical specimens were divided into four groups based on surface treatments, air-particle abrasion and grinding. After ceramic veneering half of each group were thermocycled. The bond strength was analyzed using a shear bond strength test. The surfaces were analyzed using interferometry and scanning electron microscopy. Results: The grinding procedure and air-particle abrading pressure had no significant effect on the shear bond strength (p =.264 and p =.344). Thermocycling showed a tendency towards an effect but not significant (p =.052). The group with the highest air-abrading pressure showed the highest surface roughness. No presence of an α-case layer was detected in any of the groups. Conclusion: Additively manufactured titanium grade 23 may be veneered with ceramics without prior grinding of the surfaces.
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| 42. |
- Turesson, I, et al.
(author)
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Normal tissue response to low doses of radiotherapy assessed by molecular markers--a study of skin in patients treated for prostate cancer.
- 2001
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In: Acta oncologica (Stockholm, Sweden). - 0284-186X. ; 40:8, s. 941-51
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Journal article (peer-reviewed)abstract
- The aim of this study was to evaluate normal tissue response by molecular markers to multifraction low doses of ionizing radiation, with the focus on changes in repopulation, estimated using Ki-67 as the proliferation marker, and on expressions of the p53 and p21 proteins, identified as key proteins in the DNA damage checkpoint. Repeated skin biopsies were taken from patients treated for prostate cancer with radiotherapy. The expressions of Ki-67, p53 and p21 of the keratinocytes in the basal cell layer of the epidermis were quantified immunohistochemically. The dose to the basal layer was 1.1 Gy per fraction, given five times per week for seven weeks. The indices of the three markers were determined over the whole period. A significant suppression of the Ki-67 index was observed during the first weeks, followed by a significant gradual increase in the Ki-67 index over the last weeks. The p53 and p21 protein levels were almost zero in the unirradiated skin. Upon irradiation, both the p53 and p21 index increased in a pattern very congruent to the Ki-67 index. In conclusion, daily fractions of about 1 Gy to the skin resulted in, for the keratinocytes in the basal layer, a cell growth arrest for a couple of weeks and a subsequent acceleration in repopulation during the following weeks of irradiation. The present findings also provided novel insights into the role of the p53/p21 pathway in the response of a normal epithelium to ionizing radiation as it is applied in radiotherapy.
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| 43. |
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