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- Bjohle, J, et al.
(författare)
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Serum thymidine kinase activity compared with CA 15-3 in locally advanced and metastatic breast cancer within a randomized trial
- 2013
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Ingår i: Breast Cancer Research and Treatment. - : Springer Verlag (Germany). - 0167-6806 .- 1573-7217. ; 139:3, s. 751-758
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Tidskriftsartikel (refereegranskat)abstract
- The primary objective was to estimate serum thymidine kinase 1 (TK1) activity, reflecting total body cell proliferation rate including cancer cell proliferation, in women with loco regional inoperable or metastatic breast cancer participating in a prospective and randomized study. Secondary objectives were to analyze TK1 in relation to progression-free survival (PFS), overall survival (OS), therapy response and other tumour characteristics, including CA 15-3, widely used as a standard serum marker for disease progression. TK1 and CA 15-3 were analysed in 198 serum samples collected prospectively from women included in the randomized TEX trial between December 2002 and June 2007. TK1 activity was determined by the ELISA based DiviTum (TM) assay, and CA 15-3 analyses was generated with the electrochemiluminescence immunoassay Cobas Elecsys CA 15-3 II. High pre-treatment TK1 activity predicted shorter PFS (10 vs. 15 months p = 0.02) and OS (21 vs. 38 months, p andlt; 0.0001), respectively. After adjustment for age, metastatic site and study treatment TK1 showed a trend as predictor of PFS (p = 0.059) and was an independent prognostic factor for OS, (HR 1.81, 95 % confidence interval (CI) 1.26-2.61, p = 0.001). There was a trend of shortened OS for women with high CA 15-3 (p = 0.054) in univariate analysis, but not after adjustment for the above mentioned covariates. Both TK1 (p = 0.0011) and CA 15-3 (p = 0.0004) predicted response to treatment. There were statistically different distributions of TK1 and CA 15-3 in relation to the site of metastases. TK1 activity measured by DiviTum (TM) predicted therapy response, PFS and OS in loco regional inoperable or disseminated breast cancer. These results suggest that this factor is a useful serum marker. In the present material, a prognostic value of CA 15-3 could not be proven.
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- Gielen, Marij, et al.
(författare)
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Body mass index is negatively associated with telomere length : A collaborative cross-sectional meta-analysis of 87 observational studies
- 2018
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165. ; 108:3, s. 453-475
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Tidskriftsartikel (refereegranskat)abstract
- Background: Even before the onset of age-related diseases, obesity might be a contributing factor to the cumulative burden of oxidative stress and chronic inflammation throughout the life course. Obesity may therefore contribute to accelerated shortening of telomeres. Consequently, obese persons are more likely to have shorter telomeres, but the association between body mass index (BMI) and leukocyte telomere length (TL) might differ across the life span and between ethnicities and sexes. Objective: A collaborative cross-sectionalmeta-analysis of observational studies was conducted to investigate the associations between BMI and TL across the life span. Design: Eighty-seven distinct study samples were included in the meta-analysis capturing data from 146,114 individuals. Studyspecific age- and sex-adjusted regression coefficients were combined by using a random-effects model in which absolute [base pairs (bp)] and relative telomere to single-copy gene ratio (T/S ratio) TLs were regressed against BMI. Stratified analysis was performed by 3 age categories ("young": 18-60 y; "middle": 61-75 y; and "old": >75 y), sex, and ethnicity. Results: Each unit increase in BMI corresponded to a-3.99 bp (95% CI: -5.17, -2.81 bp) difference in TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -7.67 bp (95% CI:-10.03,-5.31 bp) difference. Each unit increase in BMI corresponded to a -1.58 × 10-3 unit T/S ratio (0.16% decrease; 95% CI: -2.14 × 10-3, -1.01 × 10-3) difference in ageand sex-adjusted relative TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -2.58 × 10-3 unit T/S ratio (0.26% decrease; 95% CI: -3.92 × 10-3, -1.25 × 10-3). The associations were predominantly for the white pooled population. No sex differences were observed. Conclusions: A higher BMI is associated with shorter telomeres, especially in younger individuals. The presently observed difference is not negligible. Meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL arewarranted.
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- Baekkeskov, S, et al.
(författare)
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Antibodies to a 64,000 Mr human islet cell antigen precede the clinical onset of insulin-dependent diabetes
- 1987
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 79:3, s. 34-926
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Tidskriftsartikel (refereegranskat)abstract
- Antibodies in sera from newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients are directed to a human islet cell protein of relative molecular mass (Mr) 64,000. Since IDDM seems to develop after a prodromal period of beta-cell autoimmunity, this study has examined whether 64,000 Mr antibodies could be detected in 14 individuals who subsequently developed IDDM and five first degree relatives who have indications of altered beta-cell function. Sera were screened by immunoprecipitation on total detergent lysates of human islets and positive sera retested on membrane protein preparations. Antibodies to the 64,000 Mr membrane protein were consistently detected in 11/14 IDDM patients, and in all 5 first degree relatives. 10 IDDM patients were already positive in the first samples, obtained 4-91 mo before the clinical onset of IDDM, whereas 1 patient progressed to a high 64,000 Mr immunoreactivity, at a time where a commencement of a decline in beta-cell function was detected. 64,000 Mr antibodies were detected before islet cell cytoplasmic antibodies (ICCA) in two patients. In the control groups of 21 healthy individuals, 36 patients with diseases of the thyroid and 5 SLE patients, the 64,000 Mr antibodies were detected in only one individual, who was a healthy sibling to an IDDM patient. These results suggest that antibodies against the Mr 64,000 human islet protein are an early marker of beta-cell autoimmunity and may be useful to predict a later development of IDDM.
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- Ji, J., et al.
(författare)
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Cancer risk in hospitalized sarcoidosis patients: a follow-up study in Sweden
- 2009
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 20:6, s. 1121-1126
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sarcoidosis patients show dysregulated immune function, which may be related to subsequent cancer. We examined here the overall and specific cancer risks among Swedish subjects who had been hospitalized for sarcoidosis. Methods: A sarcoidosis research database was created by identifying hospitalized sarcoidosis patients from the Swedish Hospital Discharge Register and by linking them with the Cancer Registry. Standardized incidence ratios (SIRs) were calculated for cancers in sarcoidosis patients compared with subjects without sarcoidosis. Results: A total of 10 037 patients were hospitalized for sarcoidosis during years 1964-2004. Among them 1045 patients developed subsequent cancer, giving an overall SIR of 1.40 and 1.18 for cancer diagnosed later than 1 year of follow-up. A significant excess was noted for skin (squamous cell), kidney and nonthyroid endocrine tumors and additionally for non-Hodgkin's lymphoma and leukemia. Patients with multiple hospitalizations showed high risks. Conclusions: A 40% overall excess incidence of cancer was noted among sarcoidosis patients, but the increase was confined mainly to the first year after hospitalization. However, the increased risks of skin cancer and non-Hodgkin's lymphoma and leukemia, especially for those with multiple hospitalizations or hospitalized at old age, call for clinical attention.
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- Ji, J., et al.
(författare)
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Risk of ocular manifestations in patients with giant cell arteritis : a nationwide study in Sweden
- 2017
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 46:6, s. 484-489
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Tidskriftsartikel (refereegranskat)abstract
- Objective: No large-scale nationwide study has determined the risk of ocular manifestations in patients with giant cell arteritis (GCA). The aim was to study the incidence and risk factors of ocular manifestations in patients with GCA in Sweden. Method: A national cohort was created by linking Swedish nationwide registers. GCA patients were identified from the Swedish Hospital Inpatient and Outpatient Registers between 2002 and 2010, and were followed until the development of ocular manifestations. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated for ocular manifestations in patients with GCA compared to those without GCA. Results: We identified 3737 males and 8311 females with GCA. A total of 1618 individuals had subsequent ocular manifestations, representing 13.4% of the GCA patients. The overall SIR of ocular manifestations was 6.96 (95% CI 6.63–7.31). The risk for disorders of the optic nerve or visual tract was particularly high (SIR = 51.68, 95% CI 46.12–57.73). Men with GCA had a higher risk than women, and GCA patients without polymyalgia rheumatica (PMR) symptoms had a higher risk than those with PMR symptoms. Living outside big cities was negatively associated with ocular manifestations in GCA patients, whereas hypertension and diabetes were associated with an increased risk of ocular manifestations. Conclusion: The overall risk of ocular manifestations was higher in GCA patients than in the general population, especially for men and for those without PMR symptoms.
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- Johansson, SE, et al.
(författare)
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Smokeless tobacco and coronary heart disease: a 12-year follow-up study
- 2005
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Ingår i: European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. - : Oxford University Press (OUP). - 1741-8267. ; 12:4, s. 387-392
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Tidskriftsartikel (refereegranskat)abstract
- Background Cigarette smoking has declined whereas the use of smokeless tobacco is increasing. There is an ongoing debate as to whether smokeless tobacco is a recommendable strategy to help smokers to quit. However, very few studies have examined the association between smokeless tobacco, namely snuff, and coronary heart disease, which implies that it has not been possible to provide scientific results for public health policies and clinical guidelines concerning the use of smokeless tobacco. Design A follow-up study. Methods A random sample of 3120 healthy men aged 30–74 years was interviewed in 1988 and 1989 and followed up to the year 2000 with regard to coronary heart disease. Cox regression was used to estimate the relative risk of coronary heart disease in six categories of smoking and snuffing habits, after adjustment for established risk factors for coronary heart disease. Results Smokers, former smokers, and those who combined smoking and snuffing had significantly higher hazard ratios than never-smokers. The very highest hazard ratio was found among individuals combining smoking and snuffing. Daily snuffers had a hazard ratio of 1.62 (95% confidence interval 0.70–3.03) after adjustment for age. Conclusions Even though the association between daily snuffing and coronary heart disease was non-significant, the hazard ratio was markedly increased. Therefore, smokers should not use smokeless tobacco in order to quit smoking, especially as safer alternatives are available. Further studies in different settings are required to provide scientific results for public health policies and clinical guidelines.
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