[Metal Debris with Cobalt Intoxication and Heart Damage as a THA Complication]. / Kovový oter s otravou kobaltem a poskozením srdce jako komplikace TEP kycelního kloubu.

Total hip replacement is currently a standard orthopaedic procedure. A number of complications caused by wear of the articulating parts of the endoprosthesis were described in the past. In recent years, there have been reports of systemic manifestations of metal components wear, leading to the development of chronic metal poisoning and organ damage. Our case report documents two cases of heart damage, resulting in heart failure with the need for heart transplantation, caused by metal poisoning originating from a failed THA.

Aldehyde dehydrogenase 2 polymorphism affects the outcome of methanol poisoning in exposed humans.

As the susceptibility of humans to xenobiotics often depends on genetic factors, we assumed that ADH1B and ALDH2 genetic variants may affect susceptibility to the acute methanol exposure. To evaluate the role of genetic variants of enzymes involved in methanol catabolism in humans, we analysed ADH1B (rs1229984) and ALDH2 (rs441) polymorphisms in 50 adults who survived acute methanol poisoning, 246 individuals with alcoholic liver cirrhosis, and in 545 healthy controls. GG homozygotes of ADH1B were more common among methanol-poisoned patients (98%) and among patients with alcoholic liver cirrhosis (98%) than among healthy controls (90%) (P = 0.08 and < 0.001, respectively). Minor C allele carriers of the ALDH2 were significantly more common among methanol-poisoned persons (46%) than among patients with alcoholic liver cirrhosis or healthy controls (31% in both groups, P < 0.05 and 0.025, respectively); the odds ratios were 1.89 (95% CI 1.02-3.52) and 1.94 (1.08-3.48), respectively. As there was a substantial amount of subjects with alcohol abuse between both groups of patients, ADH1B is unlikely to affect the susceptibility to methanol poisoning. By contrast, the genetic variant of the ALDH2 enzyme seems to specifically affect the susceptibility to methanol in acutely exposed humans and potentially plays a role in the outcome of methanol poisoning.

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 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.

Countering health threats by chemicals with a potential terrorist background--creating a rapid alert system for Europe.

BACKGROUND: The acronym "ASHT" stands for "Alerting System and Development of a Health Surveillance System for the Deliberate Release of Chemicals by Terrorists". Imagine this scenario: 15 patients with respiratory symptoms following a concert in Rome and 12 patients coughing after lunch in a cafeteria in the Czech Republic; are these events related? Today these events would never be connected as there is no mechanism to allow EU Member States to share this type of information effectively. The main objective of the ASHT project was to improve data sharing between EU Member States. In part, this was achieved by an internet accessible EU-wide alerting system with the aim to detect the deliberate (i.e. criminal or terrorist) or accidental release of chemicals. Nevertheless more information from police, fire brigades and health professionals is needed. METHODS: Description of the design, development, functionality and testing of the relational database system called "RAS-CHEM" (Rapid Alert System for Chemicals). RESULTS: A database structure appropriate for the description of "events" with sophisticated retrieval functions was developed. For evaluation purposes 37 events were entered into the database including 29 scenarios and 8 historical mass intoxications. The alert level was "background information" for 21 events, "suspected mass intoxication" for 6 cases and "confirmed mass intoxication" for 10 events. CONCLUSION: The RAS-CHEM database works and will be integrated into the Health Emergency Operations Facility (HEOF) with other European Rapid Alert Systems. Poisons centres receive a large number of enquiries and could be important sentinels in this field of toxicovigilance.

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.

Supplemented creatine induces changes in human metabolism of thiocompounds and one- and two-carbon units.

The administration of creatine (5 g/day for one month) to 11 young active sportsmen affected their urinary excretion of creatine, creatinine, and thiodiglycolic acid (TDGA) as well as blood levels of homocysteine, vitamin B12 and folates. The probands were divided into four groups, according to the amount of creatine found in urine, and of folates and vitamin B12 determined in blood. The changes of folates and vitamin B12 were mutually reciprocal. Each group utilized CR as donor of one- and two-carbon (1C and 2C) units by means of homocysteine (HoCySH), folates, and vitamin B12, in different metabolic pathways. In 10 men the creatine administration was accompanied by an increase of HoCySH level in blood, while in the last man, with accidentally discovered hyperhomocysteinemia, the HoCySH level dropped by 50%. Differences between initial and terminal TDGA levels indicate that creatine affects equilibria of redox processes. Creatinine excretion into urine changed in the dependence on the extent of metabolic disturbances.

Two-year follow-up of two patients after severe thallium intoxication.

Information on the prognosis and electrophysiological follow-up of severe thallium poisoning is limited. We report two patients (mother and daughter) who were repeatedly exposed to thallium poisoning experienced hair loss, polyneuropathy, and visual impairment. Nerve conduction studies (NCSs), visual evoked potentials (VEP), brainstem auditory evoked potentials (BAEP) changes, and optical neuropathy developed within a few months latency after the first subjective signs. Normal findings of these electrophysiological methods in the first 2 weeks therefore led in one of our patients to exclusion of thallium as the cause of symptoms. Thallium poisoning was, however, later confirmed by toxicological analysis of blood and/or urine and feces in both the patients and in the microscopic hair analysis of the daughter. Both patients were treated with Prussian blue that increased the elimination of thallium in urine and feces. The hair loss was fully reversible. During a 2-year follow-up after the poisoning, polyneuropathy in the lower extremities improved substantially, but residual impairment in both motor and sensory function, NCSs, VEP, and BAEP remained. Additionally, severe asymmetrical vision impairment persists in both women, with central scotomata and impaired color discrimination in both eyes. Substantial improvement of their visual function is unlikely.

Possibilities of early diagnosis of occupational asthma.

Occupational asthma is one of the most frequent occupational diseases of the respiratory tract in developed countries. Moreover, the diagnosis of occupational asthma is difficult because the confirmation of the occupational origin of the disease has an important impact on the career of the employee and many persons must involuntarily leave their work position. To avoid serious consequences, it is necessary to develop new methods which could disclose the incipient occupational asthma earlier than methods available nowadays or support the diagnosis in case of equivocal results (decrease in ventilatory parameters) of the bronchoprovocation tests. Exhaled breath condensate (EBC) analysis is a new non-invasive method which appears useful in occupational asthma diagnostics. Leukotrienes as obstruction markers and 8-isoprostane as an oxidative stress marker could be analysed from EBC. The concentrations of leukotrienes and 8-isoprostane were described to be elevated in EBC of asthmatic persons. Monitoring of leukotrienes and 8-isoprostane concentration changes in the EBC during the bronchoprovocation tests with allergens could bring new information about the pathophysiological changes in airways during inhalation tests with allergens. Induced sputum is a relatively non-invasive method which could be used in asthma diagnosis. The monitoring of the sputum cell count (especially changes of eosinophils) has a potential to be used for monitoring of asthma and during allergen challenge tests, too. The elevation of sputum eosinophils was described after allergen tests in several studies.

Does unintentional ingestion of ethylene glycol represent a serious risk?

The objective of this study was to evaluate data retrospectively on accidental ingestion of ethylene glycol (EG), based on calls to the Czech Toxicological Information Centre and from toxicological laboratories, in the years 2000-2004. All patients who ingested a known amount of EG and/or subjects with measured serum EG levels were included. A variety of clinical and laboratory parameters was collected. The medical records of 86 subjects, who had ingested from one to three swallows of EG, were analysed. The following findings emerged-metabolic acidosis (41%), vomiting (36%), nephrotoxicity (10%), and CNS depression (9%). In 15 children, the time interval between ingestion and hospitalisation was 1 hour or less. Ethanol was given to 12 children (four as first aid), and none developed hypoglycaemia. Of the 71 adults, 93% were treated with ethanol (19 as first aid). No side effects were documented. Seventeen patients received haemodialysis (HD). Two patients recovered without HD; their EG levels were higher than in the HD-treated patients. Unintentional EG ingestion usually involves ingestion of a small amount of EG, and was connected with mild signs of intoxication. Early therapy with ethanol alone appears sufficient in such cases, and represents no risk of adverse effects.

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.

Diagnostic significance of urinary thiodiglycolic acid as a possible tool for studying the role of vitamins B12 and folates in the metabolism of thiolic substances.

We have found that the determination of thiodiglycolic acid (TDGA) in urine may help to characterize metabolic imbalance of substances participating in methionine synthesis, which leads to hyperhomocystinuria. From the metabolic scheme, based on a proper combination of known facts, we attempted to theoretically explain and to demonstrate the possibilities of TDGA formation via different ways of homocysteine transformation. This scheme was used in evaluating the results obtained by testing urine of a woman suffering from impaired function of methionine synthase reductase (CblE type of homocystinuria). The amount of TDGA excreted in her morning urine was very sensitive to the changes in her treatment based upon a combination of N5-formyl tetrahydrofolate, betaine and vitamin B12. Vitamin B12 given in the evening either alone or together with betaine increased the TDGA excretion in the morning urine up to ten times. On the other hand, in the absence of vitamin B12, betaine in combination with N5-formyl tetrahydrofolate hindered the appearance of TDGA in the morning urine. Generally, the determination of TDGA in urine of an appropriately pretreated patient may indicate the degree of success of the treatment.

Survey of Amanita phalloides poisoning: clinical findings and follow-up evaluation.

The aim of our study was to evaluate the severity of hepatic and kidney damage with a focus on their reversibility, and to analyze the prognostic factors following Amanita phalloides poisoning based on calls made to the Czech Toxicological Information Centre. A variety of clinical and laboratory parameters were collected. Student's t-test and Fisher's test were used for statistical analysis. Amanita phalloides poisoning was verified in 34 cases (5 children, 29 adults). The following findings emerged: vomiting (76%), diarrhea (62%), hepatic failure (24%), and renal failure (11%). Two patients died on the fifth day after mushroom ingestion. In 18 patients, all serum levels normalized by the time of discharge; in 10 patients up to 7.3 months on average after discharge. Five patients did not comply with follow-up. Renal damage persisted in only one patient, 19 months after discharge. In conclusion, the interval to recovery from hepatic and renal damage by the time of discharge depended on a decrease in the prothrombin index and an increase in serum transaminase and bilirubin levels. Recovery was favorable in all subjects who survived the acute phase of poisoning, except in one patient with a solitary kidney.

Complete recovery after repeated suicidal ethylene glycol ingestion.

We report here on a patient who attempted suicide four times by ingesting a lethal dose of antifreeze. Reversibility of renal damage due to ethylene glycol (EG) ingestion is not complete in all patients, and its predictor factors are not well understood. A 30-year-old man suffering from a depressive disorder repeatedly attempted suicide between 2002 and 2005. In December 2002 the patient was admitted in a coma. EG intoxication was confirmed (serum EG level 1.025 g/l) and intensive therapy was started (sodium bicarbonate, ethanol, haemodialysis). After treatment he recovered. In February 2003 this patient again drank EG (serum EG level 0.257 g/l). On admission he had no symptoms of intoxication and received only ethanol i.v. Only mild metabolic acidosis (pH = 7.365) developed. In May 2003 the patient arrived at the hospital six hours after ingestion of 500 ml of EG (serum EG level 0.282 g/l). Metabolic acidosis (pH = 7.176) and signs of nephrotoxicity (serum creatinine 168 micromol/l) had developed, for which he received intensive therapy. In May 2005 the patient was found comatose on the street. Laboratory monitoring on admission showed severe metabolic acidosis (pH = 6.899) and a serum EG level of 2.877 g/l. Intensive therapy was performed again. This case report describes for the first time the repeated ingestion of a large amount of EG by a single patient and documents the improvement of renal functions. These findings support the opinion of full recovery in patients with intensive treatment and no history of kidney damage.

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.

Ethylene glycol poisoning in the Czech Republic (2000-2002).

BACKGROUND: The objective of the study was to evaluate the severity of kidney damage retrospectively and to analyze prognostic factors following ethylene glycol (EG) poisonings. METHODS: Data concerning the clinical course of patients with EG poisoning between 2000 and 2002 were analyzed. The chi2 test, Student's t test, Fisher's test and the calculation of linear correlation coefficients were used for statistical analysis. RESULTS: Thirty-three discharge records were obtained. Three patients died, and 11 patients developed acute renal failure (mean maximum serum creatinine level 618 micromol/l). Upon discharge, serum creatinine levels were still elevated in 10 patients. In all but 1 patient, renal function completely normalized within 20 months after intoxication. CONCLUSION: Adult men are the most endangered segment of the population. The most important prognostic factors are the ingested dose and early antidotal treatment. EG toxic kidney damage is reversible.

[Severe lead intoxication after ingestion of lead shots]. / Tezká otrava olovem po pozití broku.

The authors describe severe lead intoxication in a male patient who swallowed about 20 lead shots by accident. It caused an acute lead intoxication with highest blood lead reaching about 2.4 fold value of biological exposure limit for blood lead concentration for occupational exposure (0.97 mg/l), coproporphyrines in urine reaching 30 fold increase of biological exposure limit (1000 nmol/mmol creatinine), and 5-aminolevulic acid about 2.7 fold increase of biological limit (35.0 micromol/mmol creatinine). After first dose of chelating antidote (calcium disodium edetate, EDTA) the patient excreted 9.0 mg of lead in urine during 24 hours. Clinical symptoms and results of examinations led to suspicion of gastroduodenal ulcer at first. Diagnosis was defined after detailed examination and completing of the patient's history. Typical symptoms of intoxication developed--normocytic normochromic anemia and saturnine colics. Elimination of shots from digestive tract and treatment with 8 doses of antidote led to crucial change and improvement in the course of one month. The article should serve as an instruction to early recognition of lead intoxication.

[Over-the-counter drugs in the inquiries to the Poison Information Centre]. / Lécivé látky zarazené mezi vyhrazená léciva v dotazech toxikologického informacního strediska.

The aim of the study is to assess the occurrence of inquiries to the Poison Information Centre in the years 1998-2002, concerning medical preparations containing active agents included in Act No. 79/1997 on Drugs in the group of over-the-counter (OTC) drugs which can be sold in the Czech Republic in other shops than pharmacies. It deals especially with medical preparations containing paracetamol, ibuprofen, mephenhydramine teoclate, disinfectants with iodine or 10% solutions of quaternary ammonium compounds and 3% solutions of hydrogen peroxide. The attention is focused on the quantitative assessment of inquiries, sex, age of patients, ingested dose, way of intoxication, recommended treatment and prognosis of the intoxication of the patient. The computer programme employed was established for the registrations of the calls to the Poison Information Centre. The highest number of intoxications was seen in the case of pharmaceuticals containing paracetamol and ibuprofen. The inquiries on OTC drugs that can be sold in other shops than pharmacies represent 6.3% of all calls during this five year period. The intoxication in women, suicidal attempts, ingestion of a toxic dose, rather good prognosis and a combination of several drugs predominate in the calls.

[Sodium nitrite poisoning in a neonate]. / Otrava novorozence dusitanem sodným.

Natrium nitrosum intoxication is usually associated with a subsequent methemoglobinemia. Beside it, nitrates can cause also some other pathological states. Treatment with the toluidine blue may have various adverse side effects. Newborn intoxication by natrium nitrosum developing after the intoxication of the bearing mother before the parturition has not been described yet. Our own observation is referred.