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- Henricsson, M., et al.
(author)
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Mortality in diabetic patients participating in an ophthalmological control and screening programme
- 1997
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In: Diabetic Medicine. - 0742-3071. ; 14:7, s. 576-583
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Journal article (peer-reviewed)abstract
- The aim of this follow-up study has been to assess retinopathy and change of treatment to insulin therapy as risk factors for mortality in diabetic patients participating in a control and screening programme for retinopathy. A total of 3220 diabetic patients, 483 with an age at diagnosis <30 years, and 2737 with an age at diagnosis ≤30 years, were included. Retinopathy was graded on fundus photographs using the Wisconsin Scale, and the visual acuity was assessed. The average HbA(1c) value was calculated for each patient for the previous 8 years to estimate long-term glycaemic control. Mortality data were obtained from death certificates. Two hundred and sixty-three diabetic patients (8.2 %) died during the mean follow-up time of 3.4 years, 13 (2.7 %) of those with younger-onset (<30 years) and 250 (9.1%) of those with older-onset (≤30 years) diabetes. Of them, 148 (56.3 %) died from cardiovascular and 23 (8.7 %) from cerebrovascular disorders. After adjusting for differences in age and sex, more severe retinopathy and the use of antihypertensive drugs were associated with a decreased overall survival rate as well as an increased mortality from cardiovascular and cerebrovascular diseases. A statistically significant association between HbA(tc) values in the highest quartile, i.e. ≤8.4 %, and cardiovascular and all cause mortality did not remain when retinopathy was entered into the multivariate analyses. Duration of diabetes, but not change of treatment to insulin therapy, was associated with higher cardiovascular mortality in patients whose diabetes was diagnosed after the age of 30 years. We conclude that severe retinopathy, use of antihypertensive drugs, and poor glycaemic control predicted death from cardiovascular disease in diabetic patients participating in an ophthalmological screening programme.
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- Manuguerra, M., et al.
(author)
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Multi-factor dimensionality reduction applied to a large prospective investigation on gene-gene and gene-environment interactions
- 2007
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In: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 28:2, s. 414-422
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Journal article (peer-reviewed)abstract
- It is becoming increasingly evident that single-locus effects cannot explain complex multifactorial human diseases like cancer. We applied the multi-factor dimensionality reduction (MDR) method to a large cohort study on gene-environment and gene-gene interactions. The study (case-control nested in the EPIC cohort) was established to investigate molecular changes and genetic susceptibility in relation to air pollution and environmental tobacco smoke (ETS) in non-smokers. We have analyzed 757 controls and 409 cases with bladder cancer (n = 124), lung cancer (n = 116) and myeloid leukemia (n = 169). Thirty-six gene variants (DNA repair and metabolic genes) and three environmental exposure variables (measures of air pollution and ETS at home and at work) were analyzed. Interactions were assessed by prediction error percentage and cross-validation consistency (CVC) frequency. For lung cancer, the best model was given by a significant gene-environment association between the base excision repair (BER) XRCC1-Arg399Gln polymorphism, the double-strand break repair (DSBR) BRCA2-Asn372His polymorphism and the exposure variable 'distance from heavy traffic road', an indirect and robust indicator of air pollution (mean prediction error of 26%, P < 0.001, mean CVC of 6.60, P = 0.02). For bladder cancer, we found a significant 4-loci association between the BER APE1-Asp148Glu polymorphism, the DSBR RAD52-3'-untranslated region (3'-UTR) polymorphism and the metabolic gene polymorphisms COMT-Val158Met and MTHFR-677C > T (mean prediction error of 22%, P < 0.001, mean CVC consistency of 7.40, P < 0.037). For leukemia, a 3-loci model including RAD52-2259C > T, MnSOD-Ala9Val and CYP1A1-Ile462Val had a minimum prediction error of 31% (P < 0.001) and a maximum CVC of 4.40 (P = 0.086). The MDR method seems promising, because it provides a limited number of statistically stable interactions; however, the biological interpretation remains to be understood.
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- Vaissière, Thomas, et al.
(author)
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Quantitative analysis of DNA methylation after whole bisulfitome amplification of a minute amount of DNA from body fluids.
- 2009
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In: Epigenetics : official journal of the DNA Methylation Society. - 1559-2308. ; 4:4, s. 221-30
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Journal article (peer-reviewed)abstract
- Cell-free circulating DNA isolated from the plasma of individuals with cancer has been shown to harbor cancer-associated changes in DNA methylation, and thus it represents an attractive target for biomarker discovery. However, the reliable detection of DNA methylation changes in body fluids has proven to be technically challenging. Here we describe a novel combination of methods that allows quantitative and sensitive detection of DNA methylation in minute amounts of DNA present in body fluids (quantitative Methylation Analysis of Minute DNA amounts after whole Bisulfitome Amplification, qMAMBA). This method involves genome-wide amplification of bisulphite-modified DNA template followed by quantitative methylation detection using pyrosequencing and allows analysis of multiple genes from a small amount of starting DNA. To validate our method we used qMAMBA assays for four genes and LINE1 repetitive sequences combined with plasma DNA samples as a model system. qMAMBA offered high efficacy in the analysis of methylation levels and patterns in plasma samples with extremely small amounts of DNA and low concentrations of methylated alleles. Therefore, qMAMBA will facilitate methylation studies aiming to discover epigenetic biomarkers, and should prove particularly valuable in profiling a large sample series of body fluids from molecular epidemiology studies as well as in tracking disease in early diagnostics.
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- Agaton, C., et al.
(author)
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Affinity proteomics for systematic protein profiling of chromosome 21 gene products in human tissues
- 2003
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In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 2, s. 405-
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Journal article (peer-reviewed)abstract
- Here we show that an affinity proteomics strategy using affinity-purified antibodies raised against recombinant human protein fragments can be used for chromosome-wide protein profiling. The approach is based on affinity reagents raised toward bioinformatics-designed protein epitope signature tags corresponding to unique regions of individual gene loci. The genes of human chromosome 21 identified by the genome efforts were investigated, and the success rates for de novo cloning, protein production, and antibody generation were 85, 76, and 56%, respectively. Using human tissue arrays, a systematic profiling of protein expression and subcellular localization was undertaken for the putative gene products. The results suggest that this affinity proteomics strategy can be used to produce a proteome atlas, describing distribution and expression of proteins in normal tissues as well as in common cancers and other forms of diseased tissues.
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- Alfredsson, Joakim, et al.
(author)
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Large early variation of residual platelet reactivity in Acute Coronary Syndrome patients treated with clopidogrel : Results from Assessing Platelet Activity in Coronary Heart Disease (APACHE).
- 2015
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In: Thrombosis Research. - : Pergamon Press. - 0049-3848 .- 1879-2472. ; 136:2, s. 335-340
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Journal article (peer-reviewed)abstract
- INTRODUCTION: There is a large inter-individual variation in response to clopidogrel treatment and previous studies have indicated higher risk of thrombotic events in patients with high residual platelet reactivity (HRPR), but the optimal time-point for testing is not established. The aim of this study was to investigate the optimal time-point for aggregometry testing and the risk of major adverse cardiac events associated with HRPR.METHOD AND RESULTS: We included 125 patients with ACS (73 with STEMI, and 71 received abciximab). The prevalence of HRPR varied substantially over time. The rate of HRPR in patients treated and not treated with abciximab were 43% vs 67% (p=0.01) before, 2% vs 23% (p=0.001) 6-8h after, 8% vs 9% (p=0.749) 3days after, and 23% vs 12% (p=0.138) 7-9 days after loading dose of clopidogrel. We found HRPR in 18% of the patients but only four ischemic events during 6months follow-up, with no significant difference between HRPR patients compared to the rest of the population. There were 3 TIMI major bleedings, all of which occurred in the low residual platelet reactivity (LRPR) group.CONCLUSION: There is a large variation in platelet reactivity over time, also depending on adjunctive therapy, which has a large impact on optimal time-point for assessment. We found HRPR in almost 1 in 5 patients, but very few MACE, and not significantly higher in HRPR patients. In a contemporary ACS population, with low risk for stent thrombosis, the predictive value of HRPR for ischemic events will probably be low.
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- Askling, HH, et al.
(author)
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Travellers returning to Sweden with falciparum malaria: Pre-travel advice, behaviour, chemoprophylaxis and diagnostic delay
- 2005
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In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 37:10, s. 760-765
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Journal article (peer-reviewed)abstract
- We have investigated pre-travel advice, behaviour, chemoprophylaxis and diagnostic delay in travellers returning to Sweden with falciparum malaria. Questionnaires were distributed to patients having been notified with falciparum malaria from 1994 to 2001. Of 408 notified patients, 237 (58%) returned the questionnaires; 62% were males and 43% above the age of 45 y. Africa was the travel destination in 90% of the cases, and 27% had travelled to Kenya. 69% had spent more than 1 night in the countryside, and 6% had stayed in modern urban areas only. 40% took an adequate dose of chemoprophylaxis, although this proportion decreased from 55% to 12% during the study period. Nine per cent used both bed nets and mosquito repellents regularly. The median time from onset of symptoms to contact with health care professionals was 2 d, and from that contact to start of malaria treatment the median time was less than 24 h.
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