Aim of the study: The purpose of the present work was to examine the intracellular pathway activated by SDF-1 in HuCCt cells and whether SDF-1 could act as a growth factor and/or a survival factor for HuCCt cells.Materials and Methods: HuCCt cells and primary hHSC were employed.Intracellular signaling and apoptotic pathways were investigated by Western blot analysis.Differences in the activation of different signaling proteins compared to control conditions were detected by densitometric analysis.Growth of HuCCt cells was investigated by cell count.Results: Following stimulation of HuCCt with SDF-1, the phosphorylation of Akt, Erk and JUN increased compared to control after 5 minutes and decreased at later time points.Phosphorylation of Akt and Erk was inhibited by AMD3100, a specific inhibitor of CXCR4.HSC conditioned medium (CM) induced a 30% increase of HuCCt growth compared to control, whereas stimulation with SDF-1 was without any effect.The antiapoptotic effect of SDF-1 was evaluated by measurement of cleaved-PARP and expression of Bcl-Xl in presence of an apoptotic stimulus, i.e.Arsenic trioxide (AT).AT induced apoptosis was inhibited by the coincubation of SDF-1.Conclusions: SDF-1, secreted by HSC, induces Erk, Akt and JUN phosphorylation at different time points and this coincides with a modest survival effect on HuCCt cells.

Men from the general population and male professional lorry and bus drivers were surveyed with regard to sleep habits and motor vehicle and other types of accidents. A random sample of 4000 men in the general population of Dalarna County in mid-Sweden were mailed a questionnaire and served as referents. A total of 1389 male professional lorry and bus drivers from this county responded to the same questionnaire. A total of 161 of the drivers also underwent a sleep study in their homes. The proportion of total accidents was higher among the professional drivers as compared with the males in the population, P=0.03. Reports on traffic accidents were the same in both groups, but the professional drivers reported more accidents at leisure compared with referents, P<0.0001. Accidents of any kind, traffic accidents included, among those affected by both snoring and apneas, were not reported more in either of the groups. At the sleep study, 17% of those examined received the diagnosis of obstructive sleep-apnea syndrome (OSAS). The professional drivers reported proportionally more sleep debt than the referents, P<0.001. Among referents, traffic accidents at leisure, traffic accidents while commuting and accidents at work increased in proportion to sleep debt (P<0.001, 0.006 and 0.002, respectively). The finding that self-perceived sleep debt may have an adverse effect on males in the general population and male professional drivers concerning accident likelihood should have an impact on prevention. These results stress the need to educate the general population on the importance of complying with our biological need of sleep.

Standardized diagnostic criteria determined by the International Restless Legs Syndrome Study Group were used to investigate the current prevalence of restless legs syndrome (RLS). Possible associations between RLS and neuropsychiatric and somatic complaints were also investigated. A random sample of 4,000 men living in central Sweden were sent a questionnaire that included questions about sleep habits, symptoms of sleepiness, and somatic and neuropsychiatric complaints. Four symptom questions accepted as minimal diagnostic criteria for RLS were also included. Odds (OR) ratios and 95% confidence interval (CI) for different variables were calculated by means of multivariate logistic regression; 5.8% of the men suffered from RLS. The prevalence of RLS increased with age. Sleep-related complaints were more frequent among the RLS sufferers. Complaints of headache at awakening and daytime headache were reported three to five times more frequently among RLS sufferers and there was a tendency toward reported social isolation related to RLS. Subjects with RLS more frequently reported depressed mood (OR, 2.6; 95% CI, 1.8-3.8), and complained more often of reduced libido (OR, 2.2; 95% CI, 1.4-3.3). RLS sufferers more frequently reported hypertension (OR, 1.5; 95% CI, 0.9-2.4) and heart problems (OR, 2.5; 95% CI, 1.4-4.3). Results show that restless legs syndrome is common among men. It is hypothesized that RLS may be associated with several somatic and neuropsychiatric symptoms.

A random sample of 200 women, aged 18-64 years, living in a county in mid-Sweden, was sent a questionnaire that included questions about sleep habits, symptoms of sleepiness and neuropsychiatric complaints. Standardized diagnostic criteria determined by the International Restless Legs Syndrome Study Group were used to investigate the prevalence of restless legs syndrome (RLS). Possible associations between RLS and neuropsychiatric complaints were also investigated. Odds ratios for different variables were calculated by means of multivariate logistic regression. 11.4% of the women suffered from RLS. Sleep-related complaints were more frequent among RLS sufferers than among nonsufferers. Complaints of daytime headache were reported 5 times more frequently among RLS sufferers, and there was a tendency towards social isolation related to RLS. Subjective problems in performing work due to sleepiness were ninefold among the women with RLS. These results indicate that RLS together with an association to neuropsychiatric symptoms is common among working-aged women.

The setting of OELs is part of risk management. It should, however, be kept in mind that not only scientific data affects the outcome of an OEL but also cost-benefit and technical feasibility. During the last decades, neurobehavioral methods have been used increasingly in human studies to investigate the effects of neurotoxic chemicals on the nervous system. Since exposure levels in the workplace are becoming lower and lower, traditional epidemiology will face difficulties in revealing any effects. Therefore authorities regulating chemicals must rely more and more on toxicological data and on results from experimental human studies. It will then be crucial that sound criteria for the validity of human neurobehavioral studies of neurotoxicity are established if the results from neurobehavioral studies are to be used in regulatory risk assessment. Because of the variation in individuals response to chemical exposures, exposure limits might not be possible to set with a view toward this range of susceptibility and the avoidance of any neuropathic effects. This paper discuss the Swedish experience when using neurobehavioral data in deciding effects on the nervous system as the critical effect.

Objective: The principal aim of the study was to estimate the level of exposure to organic solvents of graffiti removers, and to identify the chemicals used in different cleaning agents. A secondary objective was to inform about the toxicity of various products and to optimise working procedures. Methods: Exposure to organic solvents was determined by active air sampling and biological monitoring among 38 graffiti removers during an 8-h work shift in the Stockholm underground system. The air samples and biological samples were analysed by gas chromatography. Exposure to organic solvents was also assessed by a questionnaire and interviews. Results: Solvents identified were N-methylpyrrolidone (NMP), dipropylene glycol monomethyl ether (DPGME), propylene glycol monomethyl ether (PGME), diethylene glycol monoethyl ether (DEGEE), toluene, xylene, pseudocumene, hemimellitine, mesitylene, ethylbenzene, limonene, nonane, decane, undecane, hexandecane and γ-butyrolactone. The 8-h average exposures [time-weighted average (TWA)] were below 20% of the Swedish permissible exposure limit value (PEL) for all solvents identified. In poorly ventilated spaces, e.g. in elevators etc., the short-term exposures exceeded occasionally the Swedish short-term exposure limit values (STEL). The blood and urine concentrations of NMP and its metabolites were low. Glycol ethers and their metabolites (2-methoxypropionic acid (MPA), ethoxy acetic acid (EAA), butoxy acetic acid (BAA), and 2-(2-methoxyethoxy) acetic acid (MEAA)) were found in low concentrations in urine. There were significant correlation between the concentrations of NMP in air and levels of NMP and its metabolites in blood and urine. The use of personal protective equipment, i.e. gloves and respirators, was generally high. Conclusions: Many different cleaning agents were used. The average exposure to solvents was low, but some working tasks included relatively high short-term exposure. To prevent adverse health effects, it is important to inform workers about the health risks and to restrict the use of the most toxic chemicals. Furthermore, it is important to develop good working procedures and to encourage the use of personal protection equipment.

Women living with heavy snorers were more frequently affected by symptoms of insomnia, morning headache, daytime sleepiness, and fatigue than women living with nonsnorers. Questionnaire data were collected from 1,032 women 30 to 64 years of age residing in Dalarna county, in mid-Sweden. There were indications of a "dose-response relationship" between the conjectured sound exposure and reported symptoms, regardless of whether the female herself snored. Sleeping in separate bedrooms did not seem to give the women any alleviation. The results point to a possible contributory cause of disturbed sleep, morning headache, and daytime sleepiness among women living with a snoring spouse. The results also indicate that prevention and treatment of snoring are important issues for the couple as well as for the snorer.

OBJECTIVES The relationship between a common type of sleep disturbance, sleep-disordered breathing, and the risk of becoming involved in an occupational accident was studied. METHODS A 10-year retrospective comparison was made of occupational injuries reported to the Occupational Injury Statistics Division of the Swedish National Board of Occupational Safety and Health. The injury rates for 704 consecutive patients suffering from sleep-disordered breathing were compared with the rates for an employed, age-matched random sample of 580 subjects, drawn from the general population. RESULTS The risk of being involved in an occupational accident was about 2-fold among male heavy snorers and increased by 50% among men suffering from obstructive sleep apnea syndrome (OSAS). For females the risk increased by at least 3-fold among heavy snorers and OSAS patients. Reduced vigilance and attention due to sleep-disordered breathing are the proposed mechanisms behind the results. CONCLUSION The early identification and treatment of persons suffering from sleep-disordered breathing would not only have positive impact on individual health and well-being but also on occupational safety.

OBJECTIVES:To study the cancer incidence in a cohort of Swedish sewage workers. An increased incidence of cancer of the stomach, the kidney and the nervous system in this cohort was previously reported. This new analysis reports on 9 more years of follow up.METHODS:The study is an analysis of a cohort of all 711 employees at 17 Swedish sewage plants employed for at least for 1 year during the years 1965-86. Assessment of exposures was performed by classification of work tasks. Standardised incidence ratios (SIRs), and 95% confidence intervals (95% CIs) were calculated.RESULTS:The total cancer incidence was not significantly increased (SIR = 1.2, 95% CI 0.92 to 1.5) but the incidence of prostate cancer was (SIR = 1.6, 95% CI 1.0 to 2.5), and based on two cases only, there seemed to be a significant increase of cancer of the nose and the nasal sinuses (SIR = 12, 95% CI 1.5 to 44). The incidence of stomach cancer was also increased (SIR = 2.3, 95% CI 0.99 to 4.5). There was no relation between cancer incidence and level of sewage exposure.CONCLUSIONS:Sewage workers did not have an increased risk of cancer, and the increased risk estimates for some specific cancer sites were not conclusive.

To investigate whether Swedish sewage workers have an increased risk of respiratory symptoms or diseases. In a cross-sectional study, 149 sewage workers and 138 referents, selected from among other municipal workers, were given a self-administered questionnaire about asthma, atopy, smoking and symptoms from the airways, skin and eyes. Two-by-two statistics was used to compare proportions and logistic regression was used for multivariable analyses. The sewage workers reported significantly more adult asthma than the referents. The adjusted odds ratio for asthma during adulthood was 5.3 (95% confidence interval 1.1-26) as determined from a multivariable logistic regression analysis when controlling for age, gender, atopic disposition and tobacco smoking. They also had increased risk, but not statistically significant, of some possibly asthma related symptoms and chronic bronchitis. There was no difference in atopic disposition based on a history of allergic diseases in childhood or in parents. Neither were there any differences in symptoms in the eyes or skin. Self-reported asthma was more common among the sewage workers than other municipal workers. This might be caused by occupational exposure to irritant or inflammatory substances.

Obstructive sleep apnea syndrome (OSAS) is a significant problem for some patients presenting with snoring and excessive daytime sleepiness. The 'golden standard' therapy in OSAS is considered to be nasal continuous positive airway pressure (CPAP). The effects of CPAP on work performance in sleep apnoics has not been studied previously. One hundred and fifty-two patients with OSAS participated in an open label study. The patients were diagnosed as suffering from severe OSAS after they underwent overnight polysomnography showing that their apnea indexes were at least 20. The participants answered four questions concerning self-perceived work performance prior to and after using CPAP during 6 months. There were highly statistically significant decreases (P < 0.000001) in work performance difficulties as graded by the patient. The results of this study indicate that CPAP treatment improves subjective work performance in patients suffering from OSAS.

The objectives of the present study were to evaluate the validity of answers given in a questionnaire on musculoskeletal pain and conditions by means of a clinical assessment, and to get some understanding of the subject's perception of reported pain. This was performed by using measures of sensitivity and specificity comparing data from the questionnaire with the clinical diagnoses of conditions in the neck, shoulders and thoracic spine. Subjective perception of pain was obtained by the use of visual analogue scale (VAS) and pain drawings. For the combination of neck and shoulders, both sensitivity (95%) and specificity (88%) were high for current pain. The results of the study confirm the validity of the subjective reports of the respondents. A 'pain assessment instrument' including a questionnaire, VAS and pain drawings may be useful to reveal conditions in the neck and shoulders and thoracic spine, common sites of work related musculoskeletal disorders.

Based on theoretical estimates and various correlation studies, it has been suggested that ingestion of radon in drinking water represents an increased risk for cancer. Such a risk has never been conclusively shown in epidemiological or experimental animal studies, however, and it has been questioned whether the radon level in the drinking water is of any significance in terms of overall radon exposure. Using primary DNA damage as a biological marker for an ongoing exposure to ionising radiation, the present study was undertaken to investigate whether people with different types of residential radon exposures differed with regard to their levels of DNA damage in circulating lymphocytes. DNA damage was measured in coded blood samples from 125 residents living in 45 households with different levels of radon-222 in the drinking water (10-2410 Bq/l) and indoor air (35-1025 Bq/m3) using alkaline single cell gel electrophoresis (the 'Comet' assay). Increased levels of radon in indoor air (>200 Bq/m3) were found to be associated with an increased level of DNA damage in peripheral lymphocytes (P=0.05). No such correlation was seen for the radon concentrations in the drinking water, and there was no obvious relationship between the radon levels in drinking water and in indoor air. The results of the present study suggest that measures taken to reduce residential radon exposures should be focused on reducing radon levels in indoor air rather than minimising radon levels in drinking water.

A cross-sectional study of the renal cortex cadmium concentrations in 171 cases of sudden death showed the levels to be lower than those quoted m a Swedish report published in 1976 the reduction being more than 50 per cent among the < or = 40-year-old age group. The reduction is probably attributable to reduced smoking among. Swedes during the past few decades, though there were indications of reduced cadmium levels in non-smoking as well.

Unemployment is considered to be a public health concern since deterioration in the health of the unemployed is often anticipated. However, for some groups, such as miners, unemployment might improve health due to a cessation of potentially harmful occupational exposures. This study evaluates the health of 79 miners in one Swedish iron-ore mine, and 226 age-matched controls from the general population, during one year after the closure of the mine. The participants received a questionnaire regarding medical history and subjective symptoms at the beginning of the study period, and after one year. Statistically significant negative effects on self-reported health attributable to unemployment were not found, although neuropsychiatric symptoms were more common among the unemployed miners. The miners reported a statistically significant improvement in grip force (p = 0.031). They had a significantly higher prevalence of symptoms associated with mining related exposures when compared with the population controls; pain in the upper extremities [relative risk (RR) = 2.27, 95% confidence interval (CI) = 1.44-3.59), back pain (RR = 1.84; CI = 1.23-2.75), vasospastic disease of the fingers (RR = 2.05; CI = 1.18-3.57) and obstructive respiratory symptoms (attacks of dyspnea and wheezing: RR = 3.67; CI = 1.16-11.6).

Study objective: To investigate whether people with occupational exposure to organic solvents have a higher prevalence of obstructive sleep apnea syndrome (OSAS) than the general population and to examine the relationship between snoring and exposure to organic solvents. Design and participants: Consecutive patients, aged 30-64 years, referred during a 3-year period to the sleep laboratory at Avesta Hospital, Sweden, because of suspected OSAS made up the patient groups. Following admission, patients underwent a simplified sleep apnea investigation and were divided into two groups, OSAS (n = 320) and snorers (n = 443). A random sample of 296 men and 289 women aged 30-64 years obtained from a register of all county residents maintained by the county tax authority served as referents (controls). Both patients and referents responded to two questionnaires, including questions about occupation, exposure to organic solvents, and other chemical and physical agents. Results: Men with OSAS or snoring and women with snoring had more often been occupationally exposed to organic solvents than the referents, showing an almost twofold increase in risk for those exposed during whole workdays. For men, the risk of OSAS or snoring increased with increasing exposure. Conclusion: The result indicates that occupational exposure to organic solvents might cause sleep apnea. A new observation is that even snoring could be caused by exposure to organic solvents. It is important to elucidate whether exposure to organic solvents is a cause of OSAS, because such a finding may have important implications for prevention and treatment of sleep disturbances.

The objective of this cross-sectional study was to investigate the prevalence of abdominal symptoms and the abdominal medical history among sewage workers. 142 male sewage workers and 137 male referents in 11 Swedish municipalities were addressed with a questionnaire about abdominal symptoms, medical history, occupational history and life style factors. The sewage workers suffered less from nausea [adjusted odds ratio (adjOR) = 0.18, 95% confidence interval (Cl) 0.04-0.84] than the referents. There was no significant difference in the three months prevalence of diarrhoea (adjOR = 1.7, 95% Cl = 0.79-3.4), dyspepsia (adjOR = 0.85, 95% Cl = 0.49-1.5) or irritable bowel syndrome (adjOR = 1.4, 95% Cl = 0.53-3.5). The sewage workers were affected more often by peptic ulcers during their present jobs than the referents, although the increased risk was not significant (adjOR = 1.4, 95% Cl = 0.31-6.1). The odds ratios were adjusted for age, use of tobacco products and alcohol consumption. The conclusion of this study was that sewage workers are less affected by nausea than comparable referents.

Environmental pollution with the nephrotoxic metal cadmium is considered a potential health risk for the general population. In 1976 it was reported that the cadmium concentration in human kidney cortex in Sweden had increased in parallel with increasing levels in soil and grain during the twentieth century. Since the cadmium concentration in farming lands is still increasing, the present study was undertaken to further elucidate whether the cadmium concentration in the kidney is still increasing. Kidney cortex biopsies were collected at 171 autopsies of victims to sudden and accidental death during 1995 and 1996, and the cadmium concentrations were determined and compared with previously published Swedish data obtained from forensic autopsies. The geometric mean cadmium concentration in kidney cortex in subjects 40 years of age and younger was about 40% of the concentration found in the 1970s, while the reduction was less pronounced among older people. The highest individual concentration of cadmium was 41.5 microg/g wet weight (ww). The geometric mean concentration was less than 14 microg/g ww at ages around 50 years of age, when the cadmium concentration in kidney cortex is highest, as compared with approximately 20 microg/g ww in the 1970s. There was also a reduction in cadmium concentrations among nonsmokers; thus, a decrease in tobacco smoking in Sweden during the last decades is not the only explanation for the reduction of cadmium in the kidney cortex. Other reasons for this reduction could be changes in dietary habits and reduced cadmium contamination from Swedish industries.

OBJECTIVES:The objective of this study was to test the hypothesis that long-term occupational exposure to organic solvents may effect the levels and turnover of dopamine in man.METHODS:A study was performed on 17 patients with neuropsychiatric symptoms due to occupational solvent exposure, and 11 healthy non-exposed male volunteers (controls). Positron emission tomography (PET) was used to assess striatal dopaminergic function, using L-[11C]DOPA, [11C]nomifensine and [11C]raclopride as tracers.RESULTS:The rate of dopamine synthesis was significantly increased among subjects with occupational exposure to organic solvents compared with non-exposed controls. After controlling for the difference in age between exposed and controls, the effect of solvent exposure became less apparent and was reduced from +32% (P = 0.009) to +25% (P = 0.07). There were no differences with regard to the binding of [11C]nomifensine. Patients with and without the diagnosis of toxic encephalopathy did not differ with regard to their putaminal uptake of L-[11C]DOPA, [11C]nomifensine and [11C]raclopride.CONCLUSION:The data support the hypothesis that long-term exposure to organic solvents may increase the rate of dopamine synthesis in the brain without affecting the number of presynaptic terminals or postsynaptic dopamine receptors.

Validation of a Self‐Administered Questionnaire on Asthmatic Symptoms and Atopy in House Painters: Gunilla W ieslander , et ai. Department of Occupational and Environmental Medicine, Uppsala University —The aim of this study was to validate questions on asthmatic symptoms and atopy among Swedish house painters. Clinical investigations were performed in 44 male painters, selected by stratified sampling from a larger group of 415 painters. Symptoms were recorded by means of a self‐administered questionnaire. Clinical examinations were performed after an exposure free weekend, and included dermal prick test to nine common allergens, dynamic spirometry, and methacholine challenge test (MCT). Atopy was defined as at least one positive skin prick test to common allergens. A forced expiratory volume in one second (FEVd below 80% of normal values were considered a sign of impaired lung function. A cumulative dose of methacholine below 8 mg causing a 20% decrease in FEV t (PD 20 ) was considered a sign of bronchial hyperresponsiveness (BHR). Sensitivity and specificity for different questions was calculated. Most single airway symptom had a good sensitivity for severe BHR, defined as a PD 2 o below 0.5 mg of methacholine. For milder BHR, however, sensitivity was below 50% for most single symptoms, except the question on nonspecific hyperreactivity symptoms. By combining the symptoms to a symptom score predicable of BHR, a high sensitivity could be obtained for both mild BHR and severe BHR. Most single questions on respiratory symptoms had high specificity, but low sensitivity, as predictors of impaired FEV‐,. Sensitivity for impaired FEV‐, was improved by constructing another symptom score, predictable of FEV t . The assessment of a history of atopy by five questions on asthma, hay fever and eczema in childhood was significantly related to atopy verified by a positive dermal prick test (79% sensitivity and 75% specificity). There was also a significant relation between self‐reported hay fever and positive prick test to pollen extracts (52% sensitivity and 90% specificity). In conclusion, our questions on airway symptoms and atopy are related to clinical signs of BHR, impaired FEV 1# and atopy respectively. By combining different symptoms to symptom scores, the problem with low sensitivity of single questions on airway symptoms and atopy can be reduced.