Cognitive sequelae of methanol poisoning involve executive dysfunction and memory impairment in cross-sectional and long-term perspective.

Methanol poisoning leads to lesions in the basal ganglia and subcortical white matter, as well as to demyelination and atrophy of the optic nerve. However, information regarding cognitive deficits in a large methanol sample is lacking. The principal aim of the present study was to identify the cognitive sequelae of methanol poisoning and their morphological correlates. A sample of 50 patients (METH; age 48 ± 13 years), 3-8 months after methanol poisoning, and 57 control subjects (CS; age 49 ± 13 years) were administered a neuropsychological battery. Forty-six patients were followed in 2 years' perspective. Patients additionally underwent 1.5T magnetic resonance imaging (MRI). Three biochemical and toxicological metabolic markers and a questionnaire regarding alcohol abuse facilitated the classification of 24 patients with methanol poisoning without alcohol abuse (METHna) and 22 patients with methanol poisoning and alcohol abuse (METHa). All groups were compared to a control group of similar size, and matched for age, education, premorbid intelligence level, global cognitive performance, and level of depressive symptoms. Using hierarchical multiple regression we found significant differences between METH and CS, especially in executive and memory domains. METHa showed a similar pattern of cognitive impairment with generally more severe executive dysfunction. Moreover, all METH patients with extensive involvement on brain MRI (lesions in ≥2 anatomical regions) had a more severe cognitive impairment. From a longitudinal perspective, we did not find any changes in their cognitive functioning after 2 years' follow-up. Our findings suggest that methanol poisoning is associated with executive dysfunction and explicit memory impairment, supposedly due to basal ganglia dysfunction and disruption of frontostriatal circuitry proportional to the number of brain lesions, and that these changes are persistent after 2 years' follow-up.

Markers of oxidative damage of nucleic acids and proteins among workers exposed to TiO2 (nano) particles.

OBJECTIVE: The use of nanotechnology is growing enormously and occupational physicians have an increasing interest in evaluating potential hazards and finding biomarkers of effect in workers exposed to nanoparticles. METHODS: A study was carried out with 36 workers exposed to (nano)TiO2 pigment and 45 controls. Condensate (EBC) titanium and markers of oxidation of nucleic acids (including 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), 5-hydroxymethyl uracil (5-OHMeU)) and proteins (such as o-tyrosine (o-Tyr), 3-chlorotyrosine (3-ClTyr) and 3-nitrotyrosine (3-NOTyr)) were analysed from samples of their exhaled breath. RESULTS: In the production workshops, the median total mass 2012 and 2013 TiO2 concentrations were 0.65 and 0.40 mg/m(3), respectively. The median numbers of concentrations measured by the scanning mobility particle sizer (SMPS) and aerodynamic particle sizer (APS) were 1.98 × 10(4) and 2.32 × 10(4) particles/cm(3), respectively; and about 80% of those particles were smaller than 100 nm in diameter. In the research workspace, lower aerosol concentrations (0.16 mg/m(3) and 1.32 × 10(4) particles/cm(3)) were found. Titanium in the EBC was significantly higher in production workers (p<0.001) than in research workers and unexposed controls. Accordingly, most EBC oxidative stress markers, including in the preshift samples, were higher in production workers than in the two other groups. Multiple regression analysis confirmed an association between the production of TiO2 and the levels of studied biomarkers. CONCLUSIONS: The concentration of titanium in EBC may serve as a direct exposure marker in workers producing TiO2 pigment; the markers of oxidative stress reflect the local biological effect of (nano)TiO2 in the respiratory tract of the exposed workers.

[Occupational tuberculosis in Slovakia and in the Czech Republic]. / Profesionálna TBC na Slovensku a v Ceskej republike.

STUDY OBJECTIVE: To conduct a retrospective 15-year study to monitor trends in the number of employees at risk for occupational tuberculosis (TB) (levels III and IV) in the Slovak Republic, and in particular in the sector of economic activities Q (health care and social assistance). Furthermore, to analyze reported cases of occupational TB and to compare the incidence and sex-specific and age-specific prevalence with the data reported in the Czech Republic. MATERIAL AND METHODS: Data on the number of employees at risk of exposure to occupational TB were derived from the Automated Risk Classification System of the Slovak Republic. Data on cases of occupational TB were taken from health statistics (Institute of Health Information and Statistics/National Health Information Center in the Slovak Republic and the National Institute of Public Health in the Czech Republic). A retrospective analysis was conducted (for 1998-2012) of reported cases of occupational TB, selected from Article 24 of the List of occupational diseases (infectious and parasitic diseases except tropical infectious and parasitic diseases and diseases transmissible from animals to humans). The selection criterion was a TB diagnosis according to ICD-10. In the Czech Republic, the data were derived from Article 5.1.02 (tuberculosis), Chapter V. of the List of Occupational Diseases. The data obtained were analyzed by methods of descriptive statistics. RESULTS: The numbers of employees with a level III risk of exposure to occupational TB in the Slovak Republic declined by 30% over the 15 years of study and by 40% in category Q. In 2012, 2027 employees were classified in category III and 1442 of them belonged to group Q. Females accounted for 81-84% of employees at risk of exposure to occupational TB. Eighty-six and 181 cases of occupational TB were reported in the Slovak Republic and in the Czech Republic, respectively, in 1998-2012, with the incidence showing a downward trend in both countries. TB of the respiratory tract was reported most often (83.7% of the total of reported cases of occupational TB). As expected, more cases occurred in females than in males (1.9 times as many cases in females as in males in the Slovak Republic and three times as many cases in females as in males in the Czech Republic). The incidence of occupational TB was the highest in sector Q, with the highest absolute numbers reported in nurses. In 2012, the incidence rates of occupational TB were 0.22 cases per 100,000 sick benefit policy holders in the Slovak Republic and 0.13 cases per 100,000 sick benefit policy holders in the Czech Republic. CONCLUSION: The incidence of occupational TB has a downward trend in both countries, similarly to TB incidence in the general population. A negative aspect in both countries is the incidence of occupational TB at the middle productive age, in contrast to the population occupationally non-exposed to TB. Slovakia is surrounded by higher prevalence countries, with the exception of the Czech Republic. It cannot be ruled out that, in addition to the known factors influencing the prevalence of TB, including occupational TB, migration from eastern countries, including job search migration, can also play a role in increase in TB cases. It is vital to continue epidemiological surveillance and to reduce the risk of TB as much as possible also in healthcare settings by adhering to barrier nursing practices. Cases of active TB need early and adequately long, controlled treatment in order to reduce, among others, the incidence of multi-drug resistant TB.

Occupational skin diseases in Czech healthcare workers from 1997 to 2009.

BACKGROUND: The healthcare sector ranked in second place among economic sectors in the Czech Republic, with about 11.4 % of all occupational diseases in 2009. Skin diseases constituted about 20 % of all occupational diseases. OBJECTIVES: The aim of this study was to analyze the causes and trends in allergic and irritant-induced skin diseases in the healthcare sector. METHODS: The data concerning occupational skin diseases (Chapter IV of the Czech List of Occupational Diseases, non-infectious skin illnesses) in the healthcare sector were analyzed from the Czech National Registry of Occupational Diseases from 1997 until 2009. The trends in the total counts and most frequent causes were evaluated. RESULTS: During the past 13 years, a total of 545 skin diseases were acknowledged in healthcare workers. Allergic contact dermatitis was diagnosed in 464 (85 %), irritant contact dermatitis in 71 (13 %) and contact urticaria in 10 subjects (2 %). Ninety-five percent of the patients were females. The overall incidence in individual years varied between 1.0 and 2.9 cases per 10,000 full-time employees per year. Disinfectants were the most frequent chemical agents causing more than one third of all allergic skin diseases (38 %), followed by rubber components (32 %) and cleaning agents (10 %). CONCLUSION: A general downward trend of diagnosed cases of occupational skin diseases in heath care workers in the Czech Republic over the past 13 years was demonstrated.

LC-ESI-MS/MS method for oxidative stress multimarker screening in the exhaled breath condensate of asbestosis/silicosis patients.

The sensitive assay method was developed for a parallel, rapid and precise determination of the most prominent oxidative stress biomarkers: 8-iso-prostaglandin F(2α) a lipid oxidation biomarker, o-tyrosine an amino acid oxidation biomarker and 8-hydroxy-2'-deoxy-guanosine a nucleic acid oxidation biomarker. The method consisted of a pre-treatment part, freeze drying (lyophilization), serving the purpose of biomarkers concentration from the exhaled breath condensate and detection method LC-ESI-MS/MS, where the selected reaction-monitoring mode was used for its extremely high degree of selectivity and the stable-isotope-dilution assay for its high precision of quantification. The developed method is characterized by the following parameters: the precision was higher than 84.3% and the mean accuracy (relative error) was determined lower than 11.6%. The method was tested on samples obtained from patients diagnosed with asbestosis and silicosis, occupational diseases induced by oxidative stress, and then compared with samples from healthy subjects. The difference in biomarkers' concentration levels found between the two groups was statistically significant.

Neurological and neurophysiological examinations on workers with chronic poisoning by 2,3,7,8-TCDD: follow-up 35 years after exposure.

Between 1965 and 1968, about 350 workers were accidentally exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a chemical plant, which was producing herbicides based on the trichlorophenoxyacetic acid. About 80 workers developed signs of poisoning. The estimated mean concentration of TCDD at the time of exposure was about 5000 pg/g of plasma fat. Only 15 subjects from the original cohort remained available for the recent follow-up in 2004. All were men, mean age 60 years. The mean current TCDD plasma concentration was 128 pg/g. Neurological examination revealed some CNS impairment in eight subjects. Signs of polyneuropathy were found in nine subjects, confirmed by NCV studies in three cases. Electroencephalography was abnormal in three cases; Visual-evoked potential in five cases. Acquired dyschromatopsia was detected in six patients. SPECT showed focal reduction of perfusion in various brain locations in all but one patient. Two neuropsychological variables and the frequency of abnormal neurophysiological tests in individual patients correlated with TCDD plasma level. The findings support the hypothesis that TCDD can damage the nervous system. In addition to a direct neurotoxic effect of TCDD, changes secondary to vasculopathy should be considered, in the pathophysiology of the damage, because of the high frequency of lipid metabolism disorders and their complications.

Exposure to silica and risk of ANCA-associated vasculitis.

BACKGROUND: Exposure to silica dust is considered to be one of etiological factors of antineutrophil cytoplasmic antibodies (ANCA) -associated vasculitis (AAV). METHODS: Subjects exposed to silica dust in Central Bohemia and followed in the Department of Occupational Medicine, Charles University, were selected for study. A group of 86 men exposed to SiO2 for at least 5 years were examined. The association between occupational exposure to silica dust and ANCA positivity is analyzed. RESULTS: The subjects had a mean age of 66.7 years, and mean exposure to silica of 22.3 years. ANCA were detected significantly more frequently in patients group (17.1%; P-ANCA 18x, C-ANCA 3x) than in controls (n = 28, mean age 64.2 years, P-ANCA 1x, i.e., 3.6%). ANCA positivity was found less frequently (7.1%) in the group with history of SiO2 exposure without signs of pronounced silicosis, than in the group with simple (30.3%) or complicated silicosis (36.0%). Odds ratio for ANCA positivity and relative risk estimate in patients with silicosis were highly significant. Among possible predictor factors for ANCA positivity, silicosis and tuberculosis were relevant. No typical AAV was present among the patients. CONCLUSION: Long-term silica exposure may be one of the exogenous factors contributing to ANCA production, however, silica exposure alone, without typical silicosis, was not associated with ANCA positivity.

Mercury intoxication from skin ointment containing mercuric ammonium chloride.

OBJECTIVE: A one-year follow-up was performed of a 21-year-old man with a 16-year history of diabetes mellitus type I, who had been using ointment containing 10% mercuric ammonium chloride (hydrargyrum amidochloratum; HgNH(2)Cl) for eczema for approximately 3 weeks. Tiredness, fasciculations on the extremities and poor control of diabetes appeared after the end of the ointment treatment. Nephrotic syndrome and hypertension were diagnosed 1 month later. Two months after the ointment application the patient was very weak with tremors of the hands, almost unable to walk, and had lost 20 kg of body weight. He had severe neurasthenic symptoms and his behaviour suggested acute psychosis. METHODS: Internal, neurological and neuropsychological examinations were performed. Mercury in urine was determined by flameless atomic absorption spectrometry. RESULTS: The urine mercury level on admission was 252.0 microg/l. He was treated with Dimaval, sodium (2,3)-dimercaptopropane(-1)-sulphonate capsules for 12 days (total dose 6.3 g). The highest urine mercury excretion during antidote treatment was 2336.0 microg/24 h. The patient had proteinuria of up to 11.10 g/24 h, and renal biopsy revealed diffuse membranous glomerulonephritis of the 1st stage without apparent diabetic nephropathy. Similarly, neuropathy did not have typical signs of diabetic neuropathy. His clinical condition started to improve during the first 2 weeks. Further follow-up has shown slow normalisation of renal functions. After 1 year, proteinuria decreased to 0.62 g/24 h and body weight normalised. Neuropsychological and electromyographic findings became almost normal. CONCLUSION: Severe intoxication developed after a short period of ointment application. Most signs of damage disappeared in the course of 1 year, except mild proteinuria and neuropathy. The evolution was favourable and confirmed the primary role of mercury intoxication in the severe deterioration of the clinical status of the patient.

Lipid metabolism and neuropsychological follow-up study of workers exposed to 2,3,7,8- tetrachlordibenzo- p-dioxin.

OBJECTIVE: More than 35 years ago, during 1965-1968, in the former Czechoslovakia, approximately 80 persons became ill due to occupational exposure to 2,3,7,8-tetrachlordibenzo- p-dioxin (2,3,7,8-TCDD). The objective of this study was to investigate the incidence of disorders related to occupational exposure to 2,3,7,8-TCDD. METHODS: Most subjects in the group of 12 former 2,3,7,8-TCDD workers (mean age 56.8 years, exposure 10 days to 23 months) still suffer from disturbances of lipid metabolism, psychic disorders, chloracne, and/or nervous system lesions. All workers were given internal, neuropsychological and ophthalmological examinations. Blood cholesterol and triglycerides were measured, and the common carotid artery was examined by ultrasound (B-mode), with the intima-media thickness (IMT) also being measured. Findings were compared with the 2,3,7,8-TCDD level in 1996. RESULTS: Nine of the 12 previously exposed workers had elevated plasma lipids, and hyperlipidaemia was statistically more frequent in patients with higher 2,3,7,8-TCDD levels ( P=0.03). Subject 1, with the highest 2,3,7,8-TCDD plasma level, had 80% stenosis of the diameter of the carotid artery, which needed acute surgery. Besides him, seven persons had atherosclerotic plaques in the carotid arteries. The mean IMT in the group was 0.85 mm (SD+/-0.19); the normal value is 0.62 mm. Eight subjects had degenerative changes of the ocular fundus. Chloracne was still present in two persons. Neuropsychological findings were assessed as normal only in three persons with lower 2,3,7,8-TCDD plasma levels in 1996. Mean 2,3,7,8-TCDD plasma level in 1996 was 256 pg g(-1) fat (range 14-760). CONCLUSION: Hyperlipidaemia, atherosclerotic plaques, increased IMT, ischaemic heart disease and neuropsychological disturbances were frequent in this group of former 2,3,7,8-TCDD workers. Hyperlipidaemia might have played an important role in most of these disorders. The level of 2,3,7,8-TCDD correlated with the highest level of triglycerides ( P=0.02) and cholesterol ( P=0.01) that was found during the 35-year follow-up. This group belongs to the most heavily 2,3,7,8-TCDD-exposed groups of workers, because the mean estimated concentration at the time of intoxication was approximately 5000 pg g(-1) plasma fat.

Biochemical, neuropsychological, and neurological abnormalities following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure.

Presented herein are the results of follow-up examinations of 13 workers performed in 1996--30 yr following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication in a herbicide production plant. In these workers, the current mean plasma level of 2,3,7,8-TCDD, measured by high-resolution gas chromatography/high-resolution mass spectrometry, was 256 pg/gm lipid (range = 14-760 pg/gm lipid). This mean value corresponded to an estimated concentration of approximately 5,000 pg/gm plasma fat that existed about 30 years ago. Such a mean plasma level indicates that this group was one of the most heavily exposed groups to 2,3,7,8-TCDD described in the literature. Patients with persistent chloracne had significantly higher plasma levels of 2,3,7,8-TCDD than persons without chloracne. A significant, positive correlation was found between plasma levels of 2,3,7,8-TCDD in 1996 and levels of cholesterol and plasma lipids that existed since 1974. During 1996, there was a significant positive correlation between 2,3,7,8-TCDD and levels of beta-lipoproteins, cholesterol, and triglycerides. Also in 1996, significant correlations were found between neuropsychological variables and plasma levels of 2,3,7,8-TCDD. Other significant correlations were observed between neuropsychological variables and (1) the highest levels of triglycerides (i.e., since the year 1989), (2) levels of triglycerides in 1996, (3) levels of cholesterol at the first examination (i.e., 1969-1970), (4) highest level of cholesterol since the year 1969, and (5) cholesterol levels in 1996. Such correlations are biologically plausible, and they provide evidence of impaired cognitive performance (i.e., memory first), with a concurrent increase of plasma lipid levels. Abnormal electromyography, electroencephalography, and visual evoked potentials were observed in 23%, 54%, and 31 %, respectively, of former workers. Abnormal electroencephalography findings occurred more frequently in workers who had 2,3,7,8-TCDD blood levels that exceeded 200 pg/gm plasma fat than in workers with 2,3,7,8-TCDD values lower than 200 pg/gm plasma fat (p < .025). Frequency of polyneuropathic EMG abnormalities decreased from 38% in the 1970s to 23% in 1996. Improvement of conduction velocity in the tibial nerve was statistically significant (p < .05).

Occupational diseases in the Czech Republic in the year 1998. The need for unifying European standards/criteria for all occupational diseases.

In the Czech Republic, the Clinics and Departments for Occupational Medicine according to the legislation have the right to recognise occupational diseases. The diagnosis must correspond to the Czech list of occupational diseases, which is similar to the European list of occupational diseases. The exposure, sufficient enough to cause certain occupational disease, must be confirmed by regional industrial hygienists, responsible for hygienic control of the workplace. It is evident that the number of diseases is very much dependent upon the standards/criteria used to recognise occupational diseases. In the Czech Republic, the patients suffering from occupational diseases are given considerable financial compensations, which creates a great motivation for them to apply for occupational diseases. The article presents the overview of occupational diseases in the Czech Republic in the year 1998. The total number of diseases was 2111, the incidence per 100,000 employees was 45.8. It is necessary to present and discuss unifying criteria for occupational diseases in European countries, as well as the minimum level of the damage, that could be called an occupational disease. The criteria should be co-ordinated, because in a unified Europe, there will be many more possibilities for change in the workplace.

[Risk factors for ischemic heart disease in healthy persons with hyperinsulinemia and normal glucose tolerance]. / Rizikové faktory pro ischemickou chorobu srdecní u zdravých osob s hyperinzulinémií a normální glukózovou tolerancí.

The authors investigated the relationship of plasma insulin to some risk factors of ischaemic heart disease (IHD). They examined 79 healthy men--drivers of international truck transport with a normal glucose tolerance. The group comprised 21 men with hyperinsulinaemia. This group was compared with 21 men from the same group with normal insulin levels. The two groups were comparable (matched pairs) for age, occupation, cigarette and alcohol consumption and education. Significantly higher values of the body mass index (BMI), systolic and diastolic blood pressure were found in the group with hyperinsulinaemia. The latter group had a significantly more frequent positive family-history as regards cardiovascular diseases. After 48 months all subjects were checked. Two men from the entire group had died (43 and 48 years) from fatal myocardial infarction, both had hyperinsulinaemia. Manifestations of cardiovascular diseases (IHD and hypertension) developed in 12 subjects from the group with hyperinsulinaemia, as compared with two subjects with hypertension but normal insulin levels. To conclude, it may be stated that healthy subjects with hyperinsulinaemia and a normal glucose tolerance have a higher level of some risk factors of coronary heart disease (hypertension, obesity, positive family-history), as compared with the normoinsulinaemic group, and a poorer prognosis as regards cardiovascular morbidity and mortality.