| 1. |
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| 2. |
- Akesson, AA, et al.
(författare)
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Tubular and glomerular kidney effects in Swedish women with low environmental cadmium exposure
- 2005
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 113:11, s. 1627-1631
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Tidskriftsartikel (refereegranskat)abstract
- Cadmium is a well-known nephrotoxic agent in food and tobacco, but the exposure level that is critical for kidney effects in the general population is not defined. Within a population-based women's health survey in southern Sweden (Women's Health in the Lund Area, WHILA), we investigated cadmium exposure in relation to tubular and glomerular function, from 1999 through early 2000 in 820 women (71% participation rate) 53-64 years of age. Multiple linear regression showed cadmium in blood (median, 0.38 mu g/L) and urine (0.52 mu g/L; density adjusted = 0.67 mu g/g creatinine) to be significantly associated with effects on renal tubules (as indicated by increased levels of human complex-forming protein and N-acetyl-beta-D-glucosaminidase in urine), after adjusting for age, body mass index, blood lead, diabetes, hypertension, and regular use of nephrotoxic drugs. The associations remained significant even at the low exposure in women who had never smoked. We also found associations with markers of glomerular effects: glomerular filtration rate and creatinine clearance. Significant effects were seen already at a mean urinary cadmium level of 0.6 mu g/L (0.8 mu g/g creatinine). Cadmium potentiated diabetes-induced effects on kidney. In conclusion, tubular renal effects occurred at lower cadmium levels than previously demonstrated, and more important, glomerular effects were also observed. Although the effects were small, they may represent early signs of adverse effects, affecting large segments of the population. Subjects with diabetes seem to be at increased risk.
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| 3. |
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| 7. |
- Bonassi, Stefano, et al.
(författare)
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Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries
- 2008
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 29:6, s. 1178-1183
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Tidskriftsartikel (refereegranskat)abstract
- Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recently supported by the results of epidemiological studies that associated CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence. To overcome the limitations of single studies and to evaluate the strength of this association, a pooled analysis was carried out. The pooled database included 11 national cohorts and a total of 22 358 cancer-free individuals who underwent genetic screening with CA for biomonitoring purposes during 1965-2002 and were followed up for cancer incidence and/or mortality for an average of 10.1 years; 368 cancer deaths and 675 incident cancer cases were observed. Subjects were classified within each laboratory according to tertiles of CA frequency. The relative risk (RR) of cancer was increased for subjects in the medium [RR = 1.31, 95% confidence interval (CI) = 1.07-1.60] and in the high (RR = 1.41; 95% CI = 1.16-1.72) tertiles when compared with the low tertile. This increase was mostly driven by chromosome-type aberrations. The presence of ring chromosomes increased the RR to 2.22 (95% CI = 1.34-3.68). The strongest association was found for stomach cancer [RRmedium = 1.17 (95% CI = 0.37-3.70), RRhigh = 3.13 (95% CI = 1.17-8.39)]. Exposure to carcinogens did not modify the effect of CA levels on overall cancer risk. These results reinforce the evidence of a link between CA frequency and cancer risk and provide novel information on the role of aberration subclass and cancer type.
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| 8. |
- Bonassi, S, et al.
(författare)
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Human population studies with cytogenetic biomarkers: Review of the literature and future prospectives
- 2005
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Ingår i: Environmental and Molecular Mutagenesis. - : Wiley. - 1098-2280 .- 0893-6692. ; 45:2-3, s. 258-270
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Forskningsöversikt (refereegranskat)abstract
- Cytogenetic biomarkers are by far the most frequently used endpoints in human population studies. Their sensitivity for measuring exposure to genotoxic agents and their role as early predictors of cancer risk have contributed to this success. In this article, we present an overview of the last 25 years of population studies with cytogenetic biomarkers, describing the evolution of this research and addressing the most promising innovations for the future. The evaluation has been restricted to the most popular assays, i.e., chromosomal aberrations (CAs) and micronucleus (MN), which are considered to be causally related to early stages of chronic diseases, especially cancer, and may therefore play a major role in prevention. An extensive literature search covering the period 1 January 1980 to 31 December 2003 was performed using the Medline/PubMed database. A total of 833 population studies using CAs and 434 using matched MN inclusion criteria were included in the analysis. We report the distribution of selected papers by year of publication, country, language, agents investigated, and methods employed. The state of the art and future prospects regarding cytogenetic techniques and epidemiologic and statistical methods are discussed. The role of susceptibility and its potential impact on genotoxic damage are discussed with special attention to the effect of major genetic polymorphisms on the baseline frequency of CAs and micronuclei.
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| 9. |
- Engström, Karin, et al.
(författare)
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Arsenic metabolism is influenced by polymorphisms in genes involved in one-carbon metabolism and reduction reactions.
- 2009
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Ingår i: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. - : Elsevier BV. - 1879-2871 .- 0027-5107. ; 667, s. 4-14
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The susceptibility to arsenic (As)-induced diseases differs greatly between individuals, probably to a large extent due to genetic differences in arsenic metabolism. The aim for this study was to identify genetic variants affecting arsenic metabolism. METHODS: We evaluated the association between urinary metabolite pattern and polymorphisms in three gene-groups related to arsenic metabolism: (1) methyltransferases, (2) other genes involved in one-carbon metabolism and (3) genes involved in reduction reactions. Forty-nine polymorphisms were successfully genotyped in indigenous women (N=104) from northern Argentina, exposed to approximately 200mug/L of arsenic in drinking water, with a unique metabolism with low percent monomethylated arsenic (%MMA) and high percent dimethylated As (%DMA). RESULTS: Genetic factors affecting arsenic metabolite pattern included two polymorphisms in arsenic (+III) methyltransferase (AS3MT) (rs3740400, rs7085104), where carriers had lower %MMA and higher %DMA. These single nucleotide polymorphisms (SNPs) were in strong linkage disequilibrium (LD) with three intronic AS3MT SNPs, previously reported to be associated with arsenic metabolism, indicating the existence of a strongly methylating, population-specific haplotype. The CYP17A1 rs743572, 27kilobasepairs (kbs) upstream of AS3MT, was in strong LD with the AS3MT SNPs and thus had similar effects on the metabolite profile. Smaller effects were also seen for one-carbon metabolism genes choline dehydrogenase (CHDH) (rs9001, rs7626693) and 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) (rs1801394) and genes involved in reduction reactions, glutaredoxin (GLRX) (rs3822751) and peroxiredoxin 2 (PRDX2) (rs10427027, rs12151144). Genotypes associated with more beneficial arsenic metabolite profile (low %MMA and/or high %DMA in urine) were more common in this population, which has been exposed to arsenic in drinking water for thousands of years. CONCLUSIONS: Polymorphisms in AS3MT and in genes involved in one-carbon metabolism and reduction reactions affects arsenic metabolism.
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| 10. |
- Engström, Karin, et al.
(författare)
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Genetic variation in glutathione-related genes and body burden of methylmercury
- 2008
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Ingår i: Journal of Environmental Health Perspectives. - Research Triangle Park, N.C. : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 116:6, s. 734-739
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Exposure to toxic methylmercury (MeHg) through fish consumption is a large problem worldwide, and it has led to governmental recommendations of reduced fish consumption and blacklisting of mercury-contaminated fish. The elimination kinetics of MeHg varies greatly among individuals. Knowledge about the reasons for such variation is of importance for improving the risk assessment for MeHg. One possible explanation is hereditary differences in MeHg metabolism. MeHg is eliminated from the body as a glutathione (GSH) conjugate. OBJECTIVES: We conducted this study to assess the influence of polymorphisms in GSH-synthesizing [glutamyl-cysteine ligase modifier subunit (GCLM-588) and glutamyl-cysteine ligase catalytic subunit (GCLC-129)] or GSH-conjugating [glutathione S-transferase pi 1 (GSTP1-105 and GSTP1-114)] genes on MeHg retention. METHODS: Based on information obtained from questionnaires, 292 subjects from northern Sweden had a high consumption of fish (lean/fat fish two to three times per week or more). We measured total Hg in erythrocytes (Ery-Hg) and long-chain n-3 polyunsaturated fatty acids in plasma (P-PUFA; an exposure marker for fish intake). RESULTS: The GSTP1 genotype modified Ery-Hg; effects were seen for GSTP1-105 and -114 separately, and combining them resulted in stronger effects. We found evidence of effect modification: individuals with zero or one variant allele demonstrated a steeper regression slope for Ery-Hg (p = 0.038) compared with individuals with two or more variant alleles. The GCLM-588 genotype also influenced Ery-Hg (p = 0.035): Individuals with the GCLM-588 TT genotype demonstrated the highest Ery-Hg, but we saw no evidence of effect modification with increasing P-PUFA. CONCLUSIONS: These results suggest a role of GSH-related polymorphisms in MeHg metabolism.
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| 11. |
- Eriksson, Christer, et al.
(författare)
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Variant size- and glycoforms of the scavenger receptor cysteine-rich protein gp-340 with differential bacterial aggregation
- 2007
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Ingår i: Glycoconjugate Journal. - : Springer Science and Business Media LLC. - 1573-4986 .- 0282-0080. ; 24:2-3, s. 131-142
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Tidskriftsartikel (refereegranskat)abstract
- Glycoprotein gp-340 aggregates bacteria in saliva as part of innate defence at mucosal surfaces. We have detected size- and glycoforms of gp-340 between human saliva samples (n=7) and lung gp-340 from a proteinosis patient using antibodies and lectins in Western blots and ELISA measurements. Western blots of saliva samples, and of gp-340 purified, from the seven donors using a gp-340 specific antibody distinguished four gp-340 size variants, designated I to IV (n=2,2,2 and 1). While saliva gp-340 variants I to III had single bands of increasing sizes, variant IV and lung gp-340 had double bands. Purified I to IV proteins all revealed a N-terminal sequence TGGWIP upon Edman degradation. Moreover, purified gp-340 from the seven donors and lung gp-340 shared N-glycans, sialylated Gal beta 1-3GalNAc and (poly)lactosamine structures. However, the larger size gp-340 grouping II/III (n=4) and smaller size grouping I/IV correlated with a secretor, Se(+), and a non secretor, Se(-), dependent glycoform of gp-340, respectively (p=0.03). The Se(+) glycoforms contained ABH, Le(b), Le(y) and polylactosamine structures, while the Se(-) glycoforms lacked ABH antigens but expressed Lea, Lex and lactosamine structures. By contrast, lung gp- 340 completely lacked ABH, Le(a/b), Le(x/y) or sLe(x) structures. Gp-340 and secretor typing of saliva from additional donors (n=29) showed gp-340 glycoforms I to IV for 6, 16, 4 and 0 donors, respectively, and 3 non-typeable donors, and verified that gp-340 glycoforms I and II/III correlate with Se(-) and Se(+) phenotypes, respectively (p < 0.0001). The glycoforms of saliva and lung gp-340 mediated differential aggregation of Le(b)-(Helicobacter pylori), sialylpolylactosamine(Streptococcus suis) or sialic acid- (Streptococcus mutans) binding bacteria. In conclusion, variant size- and glycoforms of gp-340 are expressed by different individuals and may modulate the biological properties of gp-340 pertinent to health and disease.
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| 12. |
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| 13. |
- Hansson, Gert-Åke, et al.
(författare)
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Physical workload in various types of work: Part I. Wrist and forearm
- 2009
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Ingår i: International Journal of Industrial Ergonomics. - : Elsevier BV. - 0169-8141. ; 39:1, s. 221-233
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Tidskriftsartikel (refereegranskat)abstract
- The quantitative relationship between exposure to physical risk factors and upper extremity work-related musculoskeletal disorders (UE-WMSDs) is virtually unknown. To explore the variation, objective measurements were derived in 43 types of work (686 individuals), using goniometry for the wrists and electromyography (EMG) for the forearm extensor muscles. The variations due to work were great for wrist movements, wrist positions, muscular rest, as well as peak load, ranging 1.4-54 degrees/s (flexion velocity; 50th percentile), -30 degrees-3 degrees (flexion angle; 50th percentile), 0.2-23% of time, and 3.4-41% of maximal EMG (90th percentile), respectively. Even within work categories, e.g. "repetitive industrial", there were large variations for all measures. Hence, classification without measurements has limited value. All movement measures were highly correlated (vertical bar r(s)vertical bar=0.82-0.99), but only weakly so to positions (vertical bar r(s)vertical bar = 0.01-0.43). Muscular rest and "static load" (10th percentile), were highly correlated (r(s) = -0.92), but not associated to peak load (90th percentile; vertical bar r(s)vertical bar= 0.05 and 0.08, respectively). Most low-velocity work was accompanied by much muscular rest; however, the low velocity for mouse-intensive computer-work meant very little rest. Technical measurements are suitable as exposure measures in epidemiological studies, as well as a base for decisions about interventions. The multidimensional character of exposure - wrist movements, wrist postures, muscular recovery, and peak load - has to be considered. Relevance to industry: Direct measurements provide objective and quantitative measures of the main physical risk factors for UE-WMSDs, appropriate for estimating the risk, as well as giving priority to, and evaluating, interventions. (c) 2008 Elsevier B.V. All rights reserved.
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| 14. |
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| 15. |
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| 16. |
- Harari, Raul, et al.
(författare)
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Exposure and Toxic Effects of Elemental Mercury in Gold Mining Activities
- 2009
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Ingår i: Epidemiology. - : Ovid Technologies (Wolters Kluwer Health). - 1044-3983. ; 20:6, s. 264-265
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Tidskriftsartikel (refereegranskat)abstract
- Elemental mercury (Hg0) is widely used in gold-mining activities in South America, Africa and Asia. Miners use Hg0 to extract gold, and are exposed by inhalation when burning the gold amalgam to get rid of the Hg0. Burning is usually performed only once per 1–3 weeks. Gold buyers again burn the gold to be sure that they only buy gold. Hg0 affects the central nervous system (CNS), but the exposure-response relationship for discrete but important effects is not well known. As indicators of exposure, Hg levels in blood, plasma and urine are useful. It is usually assumed that there is a simple relationship between exposure and these biomarkers. However, recent data indicate that genetic traits may modify the retention of Hg. Also, there is a possibility that such factors may influence the exposure-response curves.
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| 17. |
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| 18. |
- Lannering, Birgitta, 1948, et al.
(författare)
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Classification, incidence and survival analyses of children with CNS tumours diagnosed in Sweden 1984-2005.
- 2009
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253. ; 98:10, s. 1620-7
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Primary tumours in the central nervous system (CNS) are the second most common malignancy in childhood after leukaemia. Sweden has a high incidence and a high-survival rate in international comparative studies. This has raised the question about the type of tumours included in the Swedish Cancer registry. We therefore compared international data to the Swedish Childhood Cancer registry. METHODS: Central nervous system tumours registered in the Swedish Childhood Cancer Registry were reclassified according to ICCC-3. Incidence and survival analyses were performed in the study population. RESULTS: There were 1479 children (<15 years) in Sweden diagnosed with CNS tumours 1984-2005. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 4.2/100,000 children. The survival rates have not improved significantly between the two time periods before/after 1995 (70% vs. 74%; p = 0.10). CONCLUSIONS: The mean annual incidence of children with CNS tumours was 4.2/100,000 and has not increased during the study period. Survival rate for brain tumours at 10 years follow-up was 72%.
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| 19. |
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| 20. |
- Löfstrand Grip, Rasmus
(författare)
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A mechanical model of an axial piston machine
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A mechanical model of an axial piston-type machine with a so-called wobble plate and Z-shaft mechanism is presented. The overall aim is to design and construct an oil-free piston expander demonstrator as a first step to realizing an advanced and compact small-scale steam engine system. The benefits of a small steam engine are negligible NOx emissions (due to continuous, low-temperature combustion), no gearbox needed, fuel flexibility (e.g., can run on biofuel and solar), high part-load efficiency, and low noise. Piston expanders, compared with turbines or clearance-sealed rotary displacement machines, have higher mechanical losses but lower leakage losses, much better part-load efficiency, and for many applications a more favourable (i.e., lower) speed. A piston expander is thus feasible for directly propelling small systems in the vehicular power range. An axial piston machine with minimized contact pressures and sliding velocities, and with properly selected construction materials for steam/water lubrication, should enable completely oil-free operation. An oil-free piston machine also has potential for other applications, for example, as a refrigerant (e.g., CO2) expander in a low-temperature Rankine cycle or as a refrigerant compressor. An analytical rigid-body kinematics and inverse dynamics model of the machine is presented. The kinematical analysis generates the resulting motion of the integral parts of the machine, fully parameterized. Inverse dynamics is applied when the system motion is completely known, and the method yields required external and internal forces and torques. The analytical model made use of the “Sophia” plug-in developed by Lesser for the simple derivation of rotational matrices relating different coordinate systems and for vector differentiation. Numerical solutions were computed in MATLAB. The results indicate a large load bearing in the conical contact surface between the mechanism’s wobble plate and engine block. The lateral force between piston and cylinder is small compared with that of a comparable machine with a conventional crank mechanism. This study aims to predict contact loads and sliding velocities in the component interfaces. Such data are needed for bearing and component dimensioning and for selecting materials and coatings. Predicted contact loads together with contact geometries can also be used as input for tribological rig testing. Results from the model have been used to dimension the integral parts, bearings and materials of a physical demonstrator of the super-critical steam expander application as well as in component design and concept studies.
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| 21. |
- Mertens, Fredrik, et al.
(författare)
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Prognostic significance of chromosome aberrations in high-grade soft tissue sarcomas
- 2006
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 24:2, s. 315-320
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To investigate whether previously observed correlations between tumor karyotype and risk of metastases could be reproduced in an independent set of high-grade soft tissue sarcomas (STSs). Patients and Methods In a previous study on high-grade STSs with clonal chromosome aberrations, we identified a number of cytogenetic variables, besides tumor grade and size, that were associated with significantly increased risk of metastases. In the present study, we have tested the predictive value of these cytogenetic variables in a new set of 156 high-grade STSs, all located in the extremities or trunk wall. Results Of the 10 cytogenetic variables that turned out to provide prognostic information in the previous series, encompassing 122 trunk wall or extremity STSs, three were significantly associated with metastases also in the new series. In a final Cox regression analysis including these three cytogenetic variables, as well as tumor grade and size, on the combined series of 278 high-grade STSs, four parameters were found to be significantly associated with metastasis risk: tumor grade 3, tumor size >= 5 cm, breakpoint in region 1p1, and gain of region 6p1. Conclusion Our findings suggest that independent prognostic information may be gained from cytogenetic analysis of high-grade STS.
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| 22. |
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| 23. |
- Nordander, Catarina, et al.
(författare)
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Risk of musculoskeletal disorders among females and males in repetitive/constrained work
- 2009
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Ingår i: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 52:10, s. 1226-1239
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Tidskriftsartikel (refereegranskat)abstract
- This paper combines epidemiological data on musculoskeletal morbidity in 40 female and 15 male occupational groups (questionnaire data 3720 females, 1241 males, physical examination data 1762 females, 915 males) in order to calculate risk for neck and upper limb disorders in repetitive/constrained vs. varied/mobile work and further to compare prevalence among office, industrial and non-office/non-industrial settings, as well as among jobs within these. Further, the paper aims to compare the risk of musculoskeletal disorders from repetitive/constrained work between females and males. Prevalence ratios (PR) for repetitive/constrained vs. varied/mobile work were in neck/shoulders: 12-month complaints females 1.2, males 1.1, diagnoses at the physical examination 2.3 and 2.3. In elbows/hands PRs for complaints were 1.7 and 1.6, for diagnoses 3.0 and 3.4. Tension neck syndrome, cervicalgia, shoulder tendonitis, acromioclavicular syndrome, medial epicondylitis and carpal tunnel syndrome showed PRs2. In neck/shoulders PRs were similar across office, industrial and non-office/non-industrial settings, in elbows/hands, especially among males, somewhat higher in industrial work. There was a heterogeneity within the different settings (estimated by bootstrapping), indicating higher PRs for some groups. As in most studies, musculoskeletal disorders were more prevalent among females than among males. Interestingly, though, the PRs for repetitive/constrained work vs. varied/mobile were for most measures approximately the same for both genders. In conclusion, repetitive/constrained work showed elevated risks when compared to varied/mobile work in all settings. Females and males showed similar risk elevations. This article enables comparison of risk of musculoskeletal disorders among many different occupations in industrial, office and other settings, when using standardised case definitions. It confirms that repetitive/constrained work is harmful not only in industrial but also in office and non-office/non-industrial settings. The reported data can be used for comparison with future studies.
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| 24. |
- Norppa, H., et al.
(författare)
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Chromosomal aberrations and SCEs as biomarkers of cancer risk
- 2006
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Ingår i: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. - : Elsevier BV. - 1879-2871 .- 0027-5107. ; 600:1-2, s. 37-45
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have suggested that the frequency of chromosomal aberrations (CAs), but not of sister chromatid exchanges (SCEs), predicts cancer risk. We have further examined this relationship in European cohorts comprising altogether almost 22,000 subjects, in the framework of a European collaborative project (CancerRiskBiomarkers). The present paper gives an overview of some of the results of the project, especially as regards CAs and SCEs. The results confirm that a high level of CAs is associated with an increased risk of cancer and indicate that this association does not depend on the time between CA analysis and cancer detection, i.e., is obviously not explained by undetected cancer. The present evidence indicates that both chromatid-type and chromosome-type CAs predict cancer, even though some data suggest that chromosome-type CAs may have a more pronounced predictive value than chromatid-type CAs. CA frequency appears to predict cancers at various sites, although there seems to be a particular association with gastrointestinal cancers. SCE frequency does not appear to have cancer predictive value, at least partly due to uncontrollable technical variation. A number of genetic polymorphisms of xenobiotic metabolism, DNA repair, and folate metabolism affect the level of CAs and might collectively contribute to the cancer predictivity of CAs. Other factors that may influence the association between CAs and cancer include, e.g., exposure to genotoxic carcinogens and internal generation of genotoxic species. Although the association between CA level and cancer is seen at the group level, an association probably also exists for the individual, although it is not known if an individual approach could be feasible. However, group level evidence should be enough to support the use of CA analysis as a tool in screening programs and prevention policies in occupational and environmental health.
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| 25. |
- Olsson-Strömberg, Ulla, et al.
(författare)
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Successful mobilization of Ph-negative blood stem cells with intensive chemotherapy + G-CSF in patients with chronic myelogenous leukemia in first chronic phase
- 2006
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 47:9, s. 1768-73
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to investigate the feasibility of mobilizing Philadelphia chromosome negative (Ph-) blood stem cells (BSC) with intensive chemotherapy and lenograstim (G-CSF) in patients with CML in first chronic phase (CP1). During 1994-1999 12 centers included 37 patients <56 years. All patients received 6 months' IFN, stopping at median 36 (1-290) days prior to the mobilization chemotherapy. All received one cycle of daunorubicin 50 mg/m2 and 1 hour infusion on days 1-3, and cytarabine (ara-C) 200 mg/m2 24 hours' i.v. infusion on days 1-7 (DA) followed by G-CSF 526 microg s.c. once daily from day 8 after the start of chemotherapy. Leukaphereses were initiated when the number of CD 34+ cells was >5/microl blood. Patients mobilizing poorly could receive a 4-day cycle of chemotherapy with mitoxantrone 12 mg/m2/day and 1 hour i.v infusion, etoposide 100 mg/m2/day and 1 hour i.v. infusion and ara-C 1 g/m2/twice a day with 2 hours' i.v infusion (MEA) or a second DA, followed by G-CSF 526 microg s.c once daily from day 8 after the start of chemotherapy. Twenty-seven patients received one cycle of chemotherapy and G-CSF, whereas 10 were mobilized twice. Twenty-three patients (62%) were successfully (MNC >3.5 x 10(8)/kg, CFU-GM >1.0 x 10(4)/kg, CD34+ cells >2.0 x 10(6)/kg and no Ph+ cells in the apheresis product) [n = 16] or partially successfully (as defined above but 1-34% Ph+ cells in the apheresis product) [n = 7] mobilized. There was no mortality during the mobilization procedure. Twenty-one/23 patients subsequently underwent auto-SCT. The time with PMN <0.5 x 10(9)/l was 10 (range 7-49) and with platelets <20 x 10(9)/l was also 10 (2-173) days. There was no transplant related mortality. The estimated 5-year overall survival after auto-SCT was 68% (95% CI 47 - 90%), with a median follow-up time of 5.2 years.We conclude that in a significant proportion of patients with CML in CP 1, intensive chemotherapy combined with G-CSF mobilizes Ph- BSC sufficient for use in auto-SCT.
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