Lars Rylander

Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976–1993 and on 5098 unselected cases reported in the literature 1974–2001

To ascertain the frequency of treatment-related acute myeloid leukemias and myelodysplastic syndromes (t-AML/t-MDS) in an unselected series, we have identified all adult cases analyzed in our department from 1976 to 1993. Further aims were to compare karyotypic features of t-AML/t-MDS with de novo AML/MDS, in our material as well as in 5098 unselected, cyto- genetically abnormal, published cases, and to analyze associations between type of prior therapy and karyotype. Among our 372 AML and 389 MDS, 47 (13%) were t-AML and 62 (16%) were t-MDS. Clonal abnormalities were significantly more common in t-AML and t-MDS than in de novo disease (68% vs 50%, P < 0.05 and 84% vs 45%, P < 0.001, respectively). Among the available 4230 AML and 1629 MDS (the present series and published cases), 14% were t-AML and 15% were t-MDS. In t-AML/t-MDS, the number of anomalies and the ploidy levels differed significantly from de novo cases, with complex and hypodiploid karyotypes being more common in t-AML/t-MDS. In t-AML, unbalanced changes in general, t(1;3), der(1;7), 3p−, −5, 5q−, −7, 7q−, t(9;11), t(11;19), t(11q23), der(12p), −17, der(17p), −18, and −21 were significantly more frequent than in de novo AML. In t-MDS, −5, −7, 7q−, 13q−, der(17p), and −18 were significantly more common. Type of prior treatment correlated significantly with number of anomalies in t-AML and with ploidy levels in t-AML/t-MDS. The frequencies of several aberrations varied with type of therapy, eg, 5q− was more frequent in radiotherapy-associated t-MDS, monosomy 7 was more common in t-AML and t-MDS after treatment with alkylators, and t(11q23) in t-AML was associated with topoisomerase II inhibitors. Abnormalities significantly more common in de novo disease were +8 as a sole anomaly, balanced changes in general, t(8;21), t(9;22), t(15;17), inv(16), and t(21q22) in AML, and −Y, 5q−, and 20q− as sole anomalies and +8 in MDS. The results emphasize the strong association between previous genotoxic exposure and karyotypic features.

Exposure to polybrominated diphenyl ethers and tetrabromobisphenol A among computer technicians.

This study investigates exposure to polybrominated diphenyl ethers (PBDEs) and tetrabromobisphenol A (TBBPA), which are used as flame retardants in electronic equipment, in a group of technicians with intense computer work. Thirteen PBDE congeners and TBBPA were quantified in serum from 19 computer technicians. Previously investigated groups of hospital cleaners with no computer experience, and clerks working full-time at computer screens were used for comparison. The computer technicians had serum concentrations of BDE-153, BDE-183 and BDE-209 that were five times higher than those reported among hospital cleaners and computer clerks. The median levels observed among the computer technicians were 4.1, 1.3, and 1.6 pmol/g lipid weight, respectively. In contrast, for BDE-47 there was no difference between the computer technicians and the others. BDE-100, BDE-203, and three structurally unidentified octa-BDEs and three nona-BDEs, were present in almost all samples from the computer technicians. Further, TBBPA was detected in 8 out of 10 samples. The levels of BDE-153, BDE-183, and one of the octa-BDEs were positively correlated with duration of computer work among technicians. On a group level an exposure gradient was observed, from the least exposed cleaners to the clerks, and to the highest exposed group of computer technicians. A dose (duration of computer work)-response relationship among computer technicians was demonstrated for some higher brominated PBDE congeners. Thus, it is evident that PBDEs used in computers and electronics, including the fully brominated BDE-209, contaminate the work environment and accumulate in the workers tissues.

Urinary phthalate metabolites and biomarkers of reproductive function in young men.

Background: High exposure to phthalates, which are ubiquitous contaminants, has been shown in animal studies to produce detrimental effects on male reproductive functions. A recent study in humans reported dose–response relations between low phthalate levels in urine and human semen parameters, which raises the question whether humans are more sensitive to phthalate exposure than animals. Methods: Urine, serum, and semen samples were collected from 234 young Swedish men at the time of their medical conscript examination. Semen volume, sperm concentration, and motility were measured, together with sperm chromatin integrity (sperm chromatin structure assay) and biochemical markers of epididymal and prostatic function. We analyzed reproductive hormones in serum, and mono ethyl phthalate (MEP), mono ethylhexyl phthaltale (MEHP), mono benzyl phthalate (MBzP), mono butyl phthalate (MBP), and phthalic acid in urine. Results: For MBP, MBzP, and MEHP, no clear pattern of associations were observed with any of the reproductive biomarkers. Subjects within the highest quartile for MEP had fewer motile sperm (mean difference = 8.8%; 95% confidence interval = 0.8–17), more immotile sperms (8.9%; 0.3–18), and lower luteinizing hormone values (0.7 IU/L; 0.1–1.2), but there was no suggestion of harmful effects for most other endpoints. Phthalic acid actually was associated with improved function, as measured by several markers. Conclusions: The observed weak associations between 1 phthalate biomarker and impairment of a few aspects of reproductive function biomarkers were not consistent with results from a recent U.S. study. It is not yet possible to conclude whether phthalate exposure may reflect a hazard for human male reproduction.

Evaluation of the Association between Persistent Organic Pollutants (POPs) and Diabetes in Epidemiological Studies: A National Toxicology Program Workshop Review

Background: Diabetes is a major threat to public health in the United States and worldwide. Understanding the role of environmental chemicals in the development or progression of diabetes is an emerging issue in environmental health. Objective: We assessed the epidemiologic literature for evidence of associations between persistent organic pollutants (POPs) and type 2 diabetes. Methods: Using a PubMed search and reference lists from relevant studies or review articles, we identified 72 epidemiological studies that investigated associations of persistent organic pollutants (POPs) with diabetes. We evaluated these studies for consistency, strengths and weaknesses of study design (including power and statistical methods), clinical diagnosis, exposure assessment, study population characteristics, and identification of data gaps and areas for future research. Conclusions: Heterogeneity of the studies precluded conducting a meta-analysis, but the overall evidence is sufficient for a positive association of some organochlorine POPs with type 2 diabetes. Collectively, these data are not sufficient to establish causality. Initial data mining revealed that the strongest positive correlation of diabetes with POPs occurred with organochlorine compounds, such as trans-nonachlor, dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCBs), and dioxins and dioxin-like chemicals. There is less indication of an association between other nonorganochlorine POPs, such as perfluoroalkyl acids and brominated compounds, and type 2 diabetes. Experimental data are needed to confirm the causality of these POPs, which will shed new light on the pathogenesis of diabetes. This new information should be considered by governmental bodies involved in the regulation of environmental contaminants.

Goniometer measurement and computer analysis of wrist angles and movements applied to occupational repetitive work

In epidemiological studies of occupational musculoskeletal disorders there is a need for quantitative exposure measurements of the physical work load. In studies of neck and upper limb disorders the so-called cumulative trauma disorders (CTDs), in particular the carpal tunnel syndrome, the positions and movements of the wrist are of special interest. A biaxial flexible electrogoniometer was used to measure continuously, with a sampling rate of 20 Hz, wrist flexion/extension and abduction/adduction angles up to 27 min. Evaluation of the influence of rotation on the goniometer showed some inherent crosstalk, which, however, did not invalidate the results. For occupational repetitive work, 99.5% of the signal power was contained in the 0-5 Hz band. Two-dimensional angle distributions and power spectra gave comprehensive information about wrist postures and movements. Measures reflecting both static and dynamic properties were derived from time and frequency domains. These measures give quantitative information on different potential risk factors and are therefore useful in epidemiological studies. Mean power frequency (MPF) is suggested as a generalized measure of repetitiveness. The method was applied in field studies of fish processing industry workers with highly repetitive work and risk of CTD.

Disorders of the neck and upper limbs in women in the fish processing industry

OBJECTIVE--The aim was to study the association between personal factors and physical and psychosocial work environment factors and disorders of the neck or upper limbs among women in the fish processing industry. METHODS--A cross sectional study was performed on 206 women in the fish processing industry and 208 control women. Several physical and psychosocial work environment factors were evaluated. Subjective complaints about the neck or upper limbs were assessed by questionnaire and by a clinical examination. RESULTS--The study showed a high prevalence (35%) of diagnoses in the neck or shoulders of the exposed women. All prevalence odds ratios (PORs) were substantially higher in young women. There was a pronounced dose-response relation between disorders of the neck or shoulders and duration of employment for women < 45 years old. When studying 322 former workers, the proportion who claimed musculoskeletal complaints as the reason for leaving was highest among the older women. Muscular tension, stress or worry, work strain, and the largest fraction of the work time spent with highly repetitive work tasks were clearly associated with disorders of the neck or shoulders. The measurements of the wrist movements also showed that the work was performed almost without any pauses and that the median flexion and extension velocity was high (41 degree/s). The results of observation showed good agreement with the measurements of wrist motion. CONCLUSION--Work in the fish processing industry is a risk factor for disorders of the neck and upper limbs. Due to the homogenity of the physical work load in the exposed group, we could not show any associations between the objective measurements and disorders. In cross sectional studies the risk may be underestimated due to a healthy worker effect.

Sperm chromatin structure assay as an independent predictor of fertility in vivo: a case-control study.

Standard sperm parameters have a limited power for prediction of the chance of natural conception. Recent studies have indicated that the sperm chromatin structure assay (SCSA) DNA fragmentation index (DFI), a measure for the fraction of sperms with DNA damage, is associated with fertility in vivo. The aim of this study was to evaluate the value of this parameter for prediction of infertility. One hundred and twenty-seven men from infertile couples with no known female factor and 137 men with proven fertility were included. Semen analysis was performed as recommended by the WHO. DFI was assessed using SCSA. Logistic binary regression was used to compute the odds ratios (OR) for infertility. As compared with men with a DFI <10%, men with a DFI between 10% and 20% had an increased risk for infertility (OR 2.5, 95% CI: 1.0-6.1). This was also true for men with a DFI >20% (OR 8.4; 95% CI: 3.0-23). In men with normal standard semen parameters (sperm concentration, motility and morphology) the OR for infertility was increased with DFI >20% (OR 5.1, 95% CI: 1.2-23), whereas if one of the standard semen parameters was abnormal, the OR for infertility was increased already at DFI above 10% (OR 16, 95% CI: 4.2-60). We conclude that SCSA DFI adds to the value of semen analysis in prediction of the chance of natural conception.

Fish processing work: the impact of two sex dependent exposure profiles on musculoskeletal health

OBJECTIVES: To evaluate the impact of work tasks, physical exposure, and psychosocial factors on the risk of musculoskeletal disorders in men and women, in a defined industrial setting. METHODS: 116 male and 206 female fish industry workers were compared with 129 men and 208 women with more varied work. Physical and psychosocial work load as well as musculoskeletal complaints were recorded by a questionnaire. A physical examination was performed and an observation method was used for work evaluation. 196 male and 322 female former fish processing workers received a postal questionnaire. RESULTS: The women workers in the fish industry had worse working conditions than the men for repetitiveness, constrained neck postures, and psychosocial work environment. They also had higher prevalences of complaints of the neck and shoulder (prevalence odds ratio (POR) 1.9; 95% confidence interval (95% CI) 1.1 to 3.2), neck and shoulder and elbow and hand complaints (POR 2.9; 95% CI 1.8 to 4.7 and POR 2.8; 95% CI 1.6 to 4.7, respectively). The women more often than the men left the industry because of neck and upper limb complaints. Also, women in other work had a higher prevalence of complaints of the neck and shoulder (POR 2.3; 95% CI 1.1 to 5.1) than the men. The men in the fish processing industry had a higher prevalence of complaints of the neck and shoulder than the men in other work (POR 3.6; 95% CI 1.6 to 8.0). This difference was not shown up by the questionnaire. CONCLUSIONS: Despite superficially similar work, there were clear sex differences in physical exposure and psychosocial work environment. Work in the fish processing industry was associated with a high risk of neck and upper limb disorders in women, which was probably mainly due to their extremely repetitive work tasks; the corresponding men had less repetitive work and less disorders. Also, a healthy worker effect on neck and upper limb disorders was found. The advantage of a physical examination compared with a questionnaire is clearly shown.

Muscular rest and gap frequency as EMG measures of physical exposure : the impact of work tasks and individual related factors

Owing to an orderly recruitment of motor units, low threshold type I fibres are presumed to be vulnerable in contractions of long duration. To study load on these fibres muscular rest was registered as the time fraction of electromyographic (EMG) activity below a threshold. Moreover, the frequency of periods with muscular rest, EMG gaps, was derived, since a low gap frequency has been shown to be a risk factor for musculoskeletal disorders. Trapezius EMG was registered in 24 female hospital cleaners, 21 female office workers and 13 male office workers during one working day. Cleaners have a high risk of neck/shoulder pain and had much less muscular rest than office workers measured as a percentage of total registered time (median value= 1.5%, range= 0.2-13% vs. median value= 12%, range= 0.0-32%, respectively). Gap frequency showed no difference between the two occupational groups. Both measures displayed a wide inter-individual variation. For the cleaners, some of the variance was explained by body mass index (BMI) and age, with lower values of muscular rest for older subjects with a high BMI. Among the office workers, low values of muscular rest and a high gap frequency were registered in subjects with a low subjective muscular tension tendency. Gender, strength, smoking, job strain, employment time and musculoskeletal symptoms had no impact on either EMG measure.

Impact of physical exposure on neck and upper limb disorders in female workers

Physical workload [muscular load of the trapezius and infraspinatus muscles using electromyography (EMG), wrist positions and movements by electrogoniometers] and neck and upper limb disorders (from, for example, a physical examination) were studied in women with repetitive industrial work (n = 95) and referents (n = 74). The repetitive work displayed higher ratings for wrist movements, but not for EMG. The prevalences of neck, shoulder and wrist/hand disorders were elevated for women with repetitive work [age-adjusted prevalence odds ratios (PORs) 2.0-7.5]. For the left hand, high frequency of wrist movements (mean power frequency 0.53 Hz) was associated with a high prevalence of disorders (56%), as compared to low (0.28 Hz and 26%; POR 3.5). We found no consistent and significant effect of muscular load, on either neck or shoulder disorders. However, selection and other bias may have diminished our possibility to observe such effects. Psychosocial work environment factors were not confounding the results. Measurements of wrist movements may be used for identification of high-risk work tasks.