Occupational phthalate exposure and health outcomes among hairdressing apprentices.

We studied occupational exposure to phthalates from first-morning-void urine sample of hairdressing apprentices by HPLC-MS/MS analyses and association with health status. Metabolites of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono ethyl phthalate (MEP), mono- n-butyl phthalate (MnBP) and mono-iso-butyl phthalate (MiBP) were detected in all urine samples, followed by metabolites mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono(2-etylhexyl) phthalate (MEHP) occurring in 97.06% and 86.76% of samples, respectively. Positive associations for females were observed between MnBP and fat-free mass index (FFMI) and age; negative associations were found between MEHP, MEOHP, MEHHP, sum of MEHP, MEHHP, MEOHP and vital capacity and also between MEHP and forced vital capacity (FVC of predicted value (PV)). Lengths of exposure were associated to MnBP, MEHHP, and MEP. We also documented positive associations between anthropometry (body mass index, waist-to-height ratio (WHtR), FFMI, fat mass index) and pulmonary function FVC% of PV for females and negative associations between WHtR, waist-to-hip ratio, FFMI and ratio of forced expiratory volume in 1 s (FEV1) to FVC (FEV1/FVC). We assume that factors of occupational environment of hairdressing apprentices are affected by phthalates and resulted in negative outcomes in breathing mechanism and influence of body composition. Adipose tissue could play role as confounding factor in urine excretion of phthalates because of their lipid solubility and accumulation.

Obesogenic and diabetogenic impact of high organochlorine levels (HCB, p,p'-DDE, PCBs) on inhabitants in the highly polluted Eastern Slovakia.

OBJECTIVE: This study was aimed to evaluate possible obesogenic and diabetogenic impact of highly increased serum level of persistent organochlorinated pollutants POPs, such as polychlorinated biphenyls (PCBs), dichlorodiethyl-dichloroethylene (p,p'-DDE), and hexachlorobenzene (HCB), on the level of obesity markers (cholesterol and triglyceride level in serum, and body mass index [BMI]) and diabetes markers (fasting glucose and fasting insulin in serum) in inhabitants of Eastern Slovakia. METHODS: In young (21-40 years) males (n=248) and females (n=330) as well as in old (41-75 years) males (n=586) and females (n=889), the serum levels of 15 polychlorinated biphenyl congeners (Σ15PCBs), p,p'-DDE and HCB, and serum insulin, testosterone, total cholesterol, triglycerides and glucose levels have been estimated by high resolution gas chromatography/mass spectrometry and by the appropriate electrochemiluminiscent immunoassay or chemical methods, respectively. RESULTS: In both age groups of males and females, the levels of Σ15PCBs, p,p'-DDE, and HCB were very high and their mutual interrelations were highly significant (p<0.01). However, it should be noted that no significant changes were found in individual variables related to very high level of Σ15PCBs, except of increased BMI (p>0.05) in females.In all ages and gender groups, defined above general as related to increasing level of individual OCPs in individual age and gender groups, significant increase in cholesterol and triglyceride levels as well as BMI values, supported their obesogenic effect, while significant increase in fasting glucose and insulin in serum, supported their diabetogenic effect. Finally, highly significant decrease in testosterone level, as found in both young and old males, supported the antiandrogenic effect, namely of HCB. However, somewhat less of p,p'-DDE, while PCBs did not show any such effect in spite of their very high level. CONCLUSIONS: Highly increased blood levels of diabetes (fasting glucose and insulin) and obesity markers (cholesterol, triglyceride and BMI) were found in large groups of males and females in highly polluted area of Slovakia. Significant decrease in testosterone level was also observed in males.

The kinetics of cell surface receptor expression in children perinatally exposed to polychlorinated biphenyls.

Exposure to polychlorinated biphenyls (PCBs) during pre-natal and early life can alter normal immune system development. Blood specimens from newborns, 6-, and 16-month-old infants were collected in the Michalovce and Svidnik/Stropkov districts, areas with, respectively, high and low environmental PCB contamination, and lymphocyte receptor expression was evaluated by multi-color flow cytometry. The results indicate that the percentage of lymphoid dendritic cells (DC) and naïve/resting T-lymphocytes were significantly increased at 6-months in Michalovce as compared to the same cell types in cord blood samples (p < 0.001), whereas natural regulatory T-lymphocytes and suppressor inducer T-lymphocytes were reduced (p < 0.001). Overall, a positive linear correlation of terminally differentiated effector memory (TEM) T-lymphocyte population with age, but a negative linear correlation for myeloid DC from birth to 6-months in both regions were found. Michalovce samples indicated significantly higher expression of memory T-lymphocytes (birth, 6(th), and 16(th) month), TEM T-lymphocytes (birth and 6(th) month), and lymphoid DC (6(th) month) compared to the Svidnik/Stropkov regions. After adjustment for relevant covariates, such as maternal age, parity, season of birth, breastfeeding, birth weight, and gender, the myeloid DC, suppressor inducer T-lymphocytes, truly naïve helper/inducer T-lymphocytes, and TEM T-lymphocytes remained significantly different between districts in cord blood samples. The multivariate analysis models for 6- and 16-month samples showed district differences in all cellular determinants, except for lymphoid DC and macrophage-like cells. This study provides the first evidence that pre-natal and early post-natal exposure to PCBs affects the dynamics of cell surface receptor expression on lymphoid DC and DC-like cells, suggesting impaired immunologic development following pre-natal and early post-natal PCB exposure.

Dynamics of lymphocyte subsets in children living in an area polluted by polychlorinated biphenyls.

Immune system development, particularly in the pre-natal and early post-natal periods, has far-reaching health consequences during childhood, as well as throughout life. Exposure to poly-chlorinated biphenyls (PCBs) during pre-natal and early life has been previously associated with changes in the incidence of infectious and allergic diseases in children, and humoral immunity alterations. Lymphocyte immunophenotyping is an important tool in the diagnosis of immunologic and hematologic disorders. This study used a lysed whole blood method for analysis of lymphocyte sub-populations in samples from children born and living in two districts: a highly-contaminated area (Michalovce) and one (Svidnik/Stropkov) with ≈ 2-fold lower environmental PCB levels. The percentages of B-lymphocytes (CD19(+)), activated HLADR(+)CD19(+) cells, and CD8(+) T-lymphocytes significantly increased at 6- and 16-months-of-age in both selected regions as compared to in cord blood values (p < 0.001). Levels of CD3(+) cells increased significantly (from 61 to 65%) in samples from Michalovce (p < 0.01). Levels of CD4(+) T-lymphocytes declined 10% among 16-month-olds in both regions (Michalovce at p < 0.001 and Svidnik/Stropkov at p < 0.01). Natural killer (NK) cell levels decreased 50% in Michalovce 6- and 16-month-old children and 42% among 6-month-olds in Svidnik/Stropkov (p < 0.001). Compared with the less-contaminated region, Michalovce samples showed significantly higher expression of CD3(+) T-lymphocytes, B-lymphocytes, and activated B-lymphocytes, whereas NK cells were less expressed. Even after adjustment for selected covariates, e.g., maternal cigarette smoking, age, parity, ethnicity, birth weight, and gender of infant, the levels of CD19(+), HLADR(+)CD19(+), and CD3(-)CD(16 + 56)(+) cells were seen to remain significantly different between the districts. These results showed that early-life environmental PCB exposure was associated with fluctuations in major lymphocyte subsets in children, suggesting that there is a post-natal immune system response to PCB exposures.

High prevalence of prediabetes and diabetes in a population exposed to high levels of an organochlorine cocktail.

AIMS/HYPOTHESIS: A heavily polluted area of Eastern Slovakia was targeted by the PCBRISK cross-sectional survey to search for possible links between environmental pollution and both prediabetes and diabetes. METHODS: Associations of serum levels of five persistent organic pollutants (POPs), namely polychlorinated biphenyls (PCBs), 2,2'-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE), 2,2'-bis(4-chlorophenyl)-1,1,1-trichloro-ethane (p,p'-DDT), hexachlorobenzene (HCB) and beta-hexachlorocyclohexane (beta-HCH), with prediabetes and diabetes were investigated in 2,047 adults. Diabetes and prediabetes were diagnosed by fasting plasma glucose in all participants and by OGTT in 1,220 compliant participants. RESULTS: Our population was stratified in terms of individual POPs quintiles and associations between environmental pollution, prediabetes and diabetes were investigated. Prevalence of prediabetes and diabetes increased in a dose-dependent manner, with individuals in upper quintiles of individual POPs showing striking increases in prevalence of prediabetes as shown by OR and 95% CI for PCBs (2.74; 1.92-3.90), DDE (1.86; 1.17-2.95), DDT (2.48; 1.77-3.48), HCB (1.86; 1.7-2.95) and beta-HCH (1.97; 1.28-3.04). Interestingly, unlike PCBs, DDT and DDE, increased levels of HCB and beta-HCH seemed not to be associated with increased prevalence of diabetes. Nevertheless, individuals in the 5th quintile of the variable expressing the cumulative effect of all five POPs (sum of orders) had a more than tripled prevalence of prediabetes and more than six times higher prevalence of diabetes when compared with the 1st referent quintile. CONCLUSIONS/INTERPRETATION: Increasing serum concentrations of individual POPs considerably increased prevalence of prediabetes and diabetes in a dose-dependent manner. Interaction of industrial and agricultural pollutants in increasing prevalence of prediabetes or diabetes is likely.

Human exposure to polyhalogenated hydrocarbons and incidence of selected malignancies -central European experience.

This paper describes results of two ecological studies design to analyze the incidence of selected malignancies in two populations exposed to polychlorinated hydrocarbons, mostly PCBs and TCDDs/Fs by comparing data available in the National Cancer Registry of the Slovak Republic and National Oncological Registry of the Czech Republic databases for the Slovak Republic (approximately 5M inhabitants) and the Czech Republic (10,3 M inhabitants) to the data relevant for the population of Michalovce District, the Slovak Republic (approximately 112,000 inhabitants) and Uherske Hradiste, the Czech Republic (146,000 inhabitants). Those districts are recognized as PCB-contaminated areas due to production and industrial use of PCBs. Data were analyzed for the 10-year period 1987-1996. The age adjusted world standard ratio (WSR) incidence of thyroid, pancreatic, breast, ovarian, bladder, and brain tumors in females and thyroid, pancreatic, breast, bladder, brain, prostate and testicular tumors in males were compared. Neither PCBs nor TCDDs/Fs appear to contribute to the observed significantly lower incidence of breast and prostate cancer in the Michalovce District and lower bladder cancer incidence in Uherske Hradiste District. However, anti-estrogenic and anti-androgenic properties have been described for hydroxylated and methylsulfonyl PCB metabolites. These properties could contribute to a mechanism through which these metabolites might modulate the development of breast, prostate and bladder cancer. The results of our analysis points to substantial potential problems of risk assessment for cancer incidence in populations exposed to xenobiotics, or more generally, as it relates to a wide spectrum of confoundings of cancer risk factors.

Multiple organochlorine pollution and the thyroid.

OBJECTIVE: Although the biological effects of major persistent organochlorinated pollutants (POPs) appear to be essentially similar, some effects which would be specific for certain substance cannot be excluded. We attempted to study the thyroid volume and thyrotropin level in the population living in the area with multiple pollution by polychlorinated biphenyls (PCBs) and pesticides (DDE and hexachlorobenzene - HCB). METHODS: A total of 454 adults was examined within the pilot field survey in 1998. Among them were 237 males (age range 19-78 years, median 47) and 227 females (age range 19-78 years, median 48). Fifteen environmentally prevalent congeners of polychlorinated biphenyls and also p,p-DDE (2,2-bis(4-chlorophenyl)-1,1-dichloroethylene), p,p-DDT (2,2-bis(4-chlorophenyl)- 1,1,1-trichloro-ethane), hexachlorobenzene (HCB) as well as alpha-, beta- and gamma-hexachlorocyclohexane (HCH) were determined in serum by high resolution gas chromatography using microelectron capture detector and microcapillary column. Thyroid volume (ThV) was measured by real time sonography using the ellipsoid method with the aid of sonographic instrument Sonoline SI-400 (Siemens, Germany). The level of TSH was estimated by supersensitive immunoradiometric method using commercial kits by Immunotech (Marseille, France). Pearsons correlation coefficients after logarithmic transformation of values and Spearmans correlation coefficients were used for statistical evaluation. RESULTS: Significant positive association (p<0.01) was found between DDE and PCB, DDE and HCB, while that between PCB and HCB was not significant. Similar positive association (p<0.01) was also found between each individual organochlorine and their sum. Significant negative association (p<0.01) was found between ThV and TSH. When using categorical PCB values either >2000 (N=208) or >3000 (N=127) ng/g lipid, significant positive association (p<0.05 and p<0.01, respectively) was found between the sum of all organochlorines (PCB+DDE+HCB) and ThV, while that between PCB and ThV (p<0.01) was found only at the PCB levels >3000 ng/g lipid. When using Spearmans correlation coefficients, significant negative association appeared between PCB and TSH (p<0.05), sum of organochlorines and TSH (p<0.05) and ThV and TSH (p<0.01). CONCLUSIONS: Although several significant positive and negative associations were found, this study, like several others, could not exactly define the participation level of individual POPs in their common toxic effects, but possibly contributed to the recognition and elucidation of some problems related to this task.

Insulin sensitivity indices: a proposal of cut-off points for simple identification of insulin-resistant subjects.

Demanding measurement of insulin sensitivity using clamp methods does not simplify the identification of insulin resistant subjects in the general population. Other approaches such as fasting- or oral glucose tolerance test-derived insulin sensitivity indices were proposed and validated with the euglycemic clamp. Nevertheless, a lack of reference values for these indices prevents their wider use in epidemiological studies and clinical practice. The aim of our study was therefore to define the cut-off points of insulin resistance indices as well as the ranges of the most frequently obtained values for selected indices. A standard 75 g oral glucose tolerance test was carried out in 1156 subjects from a Caucasian rural population with no previous evidence of diabetes or other dysglycemias. Insulin resistance/sensitivity indices (HOMA-IR, HOMA-IR2, ISI Cederholm, and ISI Matsuda) were calculated. The 75th percentile value as the cut-off point to define IR corresponded with a HOMA-IR of 2.29, a HOMA-IR2 of 1.21, a 25th percentile for ISI Cederholm, and ISI Matsuda of 57 and 5.0, respectively. For the first time, the cut-off points for selected indices and their most frequently obtained values were established for groups of subjects as defined by glucose homeostasis and BMI. Thus, insulin-resistant subjects can be identified using this simple approach.

Human thyroid in the population exposed to high environmental pollution by organochlorinated pollutants for several decades.

OBJECTIVE: To study possible effects of long-time exposure of chemical factory employees and population of surrounding polluted area to polychlorinated biphenyls and pesticides on the thyroid volume and function as compared to the population from the area of background pollution. METHODS: A total of 461 adults consisting of 239 men and 222 women was examined and divided into four groups according to their permanent domicile as related to the level of environmental pollution, e.g. SR (area of background pollution, n = 207), SI (slightly polluted area, n = 59), MI (polluted city of Michalovce, n = 94) and CH (employees of chemical factory subjected to high PCB exposure, n = 101), combined first three groups being also called LPA (less polluted areas, n = 360). Thyroid volume (ThV) and echogenicity were measured by real time sonography. The level of polychlorinated biphenyls (PCB) and pesticides (hexachlorbenzene--HCB, DDE (2,2'-2-bis(4-chlorobiphenyl)- 1,1-dichloroethylene), p,p'-DDT (2,2'-bis(4-chlorophenyl)- 1,1,1-trichloroethane) and alpha-, beta- and gamma-hexachlorcyclohexane--HCH) was estimated by congener specific analysis using HP 5890 gas chromatograph with a 63Ni electron capture detector. Serum levels of thyrotropin (TSH) and thyroid peroxidase antibodies (anti-TPO) were measured by specific sensitive immunoassays. RESULTS: The association of very high PCB level (e.g. 7300 +/- 871 ng/g lipid; mean +/- S.E.) with increased ThV (e.g. 16.3 +/- 0.73 ml) in CH has been found, the values being significantly higher than these of 360 subjects in LPA (e.g. 2045 +/- 147 ng/g, p < 0.001 for PCB and 14.0 +/- 0.32 ml, p < 0.001 for ThV). In 23 subjects from CH with PCB level > 10000 ng/g the ThV was 18.7 +/- 2.32 ml, while that in 251 subjects from LPA with PCB level of < 2000 ng/g was 13.8 +/- 0.35 ml (p < 0.05). In addition, ThV as well as PCB levels were strikingly increasing with age. In parallel with PCB levels, also the levels of other organochlorines estimated (namely these of DDE) were increasing. Although the participation of these substances in the development of adverse effects cannot yet be defined, it cannot be excluded. The association of increased levels of episodic congener PCB 101 with increased ThV appeared to be more pronounced than that of stable congeners PCB 153 and 180. Finally, significant increase in the frequency of thyroid hypoechogenicity by ultrasound, ThV > 20.0 ml and thyroperoxidase antibodies in CH area was observed as compared to LPA. CONCLUSIONS: Several associations of high PCB and pesticides level with characteristics of thyroid disorders (e.g. increased thyroid volume, frequency of hypoechogenicity and frequency of positive thyroperoxidase antibodies level in blood) were observed in the area with heavy industrial pollution by PCB.

From naturally occurring goitrogens to the effects of anthropogenic endocrine disruptors on the thyroid in Slovakia.

The objective is to describe the effect of mandatory and well monitored prophylaxis of endemic goitre in Slovakia with the use of iodised salt for past 50 years and previous experimental attempts to assess a possible participation of naturally occurring goitrogens in the etiology of goitre. Previous observations by others showed a striking decrease of goitre prevalence in schoolchildren as early as few years after starting the prophylaxis in Slovakia and this success has been confirmed by a European study conducted by others in mid nineties. In the meantime, however, massive industrialisation of Slovakia and environmental negligence of the administration resulted in heavy airborne and mainly waterborne pollution of the food chain in certain areas around large chemical factories by industrial waste including polychlorinated biphenyls (PCB). Since Slovakia has been recently evaluated as an iodine replete country as based on the findings of the low thyroid volume by ultrasound and high urinary iodine, it became possible to evaluate the participation of factors different from iodine deficiency in the thyroid growth. Recent field surveys including an extensive international study PCBRISK repeatedly showed highly increased blood PCB level in subjects living in the polluted area and, at the same time, increased thyroid volume by ultrasound, increased frequency of positive thyroid antibodies and impaired glucose tolerance. (Ref. 59)

Thyroid function and cholesterol level: paradoxical findings in large groups of population with high cholesterol food intake.

OBJECTIVE: To compare the levels of serum cholesterol with thyroid function as estimated by the level of thyrotropin and free thyroxine with possible participation of thyroperoxidase antibodies in large number of adults examined within large field surveys focused on the evaluation of thyroid status of Slovak rural population. SUBJECTS AND METHODS: Serum level of cholesterol and thyrotropin (TSH) was estimated in a total of 2786 adults. In addition, in 2038 of them also the level of free thyroxine (FT4), total triiodothyronine (TT3), cholesterol, triglycerides and phospholipids was measured. The levels of TSH, anti-TPO and FT4 were estimated by supersensitive electrochemiluminiscent immunoassay using the automatic system Elecsys (Roche, Switzerland). RESULTS: A total of 2786 adults was stratified into 7 groups according to the range of TSH level as related to generally recognized level of thyroid function, e.g. 1. TSH <0.10 mU/L (overt hyperthyroidism, N=41), 2. TSH 0.11-0.30 mU/L (overt or subclinical hyperthyroidism, N=149), 3. TSH 0.31-2.50 mU/L (normal level, N=1750), 4. TSH 2.51-4.50 ("high normal" level, N=607), 5 TSH 4.51-6.50 (mild or incipient subclinical hypothyroidism, N=137), 6. TSH 6.51-10.00 mU/L (mild hypothyroidism, N=50), 7. TSH 10.01-99.00 mU/L (severe hypothyroidism, N=53). The average levels of cholesterol in all groups were very similar ranging from 5.53 to 6.17 mmol/L and no interrelations with TSH level were found. In addition, no considerable differences between these groups were found when considering the levels of medians, upper quartiles and 90th percentiles of individual groups. When male and female subjects were divided into age groups according to the decades, an age dependent increase of cholesterol level was found in both sexes. The fraction of 2038 subjects was divided into the same TSH related groups as defined above. Similarly as above, no considerable differences in cholesterol, triglycerides and phospholipids level were observed. However, the levels of FT4 and TT3 were significantly decreasing with the increase of TSH level which confirmed the continuing decrease of thyroid function. The frequency of positive anti-TPO in subjects with TSH >6.5 mU/l (71/86 = 82.5%) was significantly higher than that in subjects with TSH <6.5 mU/l (468/1952 = 23.9%). CONCLUSIONS: No difference in the level of cholesterol and triglycerides was found in large groups of rural adults from Slovakia with various thyroid function as estimated by the level of TSH, FT4, TT3 and anti-TPO. It is assumed that this interrelation resulted from very high cholesterol intake due to inappropriate general nutritional status of rural population resulting from the consumption of unhealthy foods.

[Early diagnosis and reasons for not administering thrombolytic therapy in acute myocardial infarct]. / Vcasná diagnóza a príciny nerealizácie trombolytickej liecby u chorých s akútnym infarktom myokardu.

In Slovakia we are lacking data on early (before examination of serum markers of myocardial necrosis) pertaining to thrombolytic treatment (TLL) which is inevitable in case of acute myocardial infarction (AIM) as well as data on the reasons why TLL is not implemented. This why the authors analyze the results of completed comprehensive project Audit concerned with diagnostic and therapeutic procedures in patients with acute coronary syndromes during the pre-hospital and hospital stage (AUDIT). The investigation was a perspective multi-centre study. Data were collected from 3123 patients with AIM in 66 departments (in 64 health institutions) during Sept. 16 1997 till Sept. 15 1998. The group included patients admitted within 96 hours after the development of complaints with the diagnosis or suspicion of AIM and discharged with the diagnosis of a first/repeated AIM. Early diagnosis of AIM was made in 1736 (55.6%) patients. In the AUDIT study TLL was assessed in 1074 (34.6%) patients. A marked difference between the number of candidates for TLL and the number of patients with TLL where TLL was implemented requires that in analyses of TLL in patients with AIM attention should be paid also to reasons why it was not implemented. The most frequent cause why TLL was nor implemented was late admission of the patient to hospital (in patients who attended hospital < 6 hours, TLL was not implemented in 48.5%, after admission between 6 and 12 hours in 70% and in patients admitted > 12 hours in as many as 90.8% patients), equivocal indication of TLL (in 29.9% patients) and contraindications (in 16.1% patients). The presented results are priority data on the early diagnosis of AIM and reasons why TLL was not implemented. It is part of data essential needed for elaboration of a (national) programme of better care (management) of patients with AIM taking into account also economic factors.

[Effect of demographic, anamnestic and clinical factors on hospital mortality in patients with myocardial infarct]. / Ovplyvnenie nemocnicnej smrtnosti chorých s akútnym infarktom myokardu demografickými, anamnestickými a klinickými faktormi.

The objective of the work was to analyze local priority data on the possible effect of demographic, anamnestic and clinical factors in a non-selected population of 3123 patients with acute myocardial infarction (AIM) on the hospital mortality (HM). 12.6% patients with AIM died in hospital. The mean age of those who died was 71.92 years. There were more than 4 times more patients above 64 years than 64-year-old ones or younger ones who died. The mortality rate of 64-year-old patients and younger ones (5.2% is significantly lower than in patients above 64 years (19%). The mortality rate of patients above 74 years was 27.1%. Important correlations of the HM were moreover found--in women, patients living permanently in rural areas, in widowed subjects, in patients with elementary education, old age, pensioners and non-smokers. The HM was lower (< 10%) in patients with a history of complex ventricular arrhythmias, impaired lipid metabolism and those who had no other serious disease in the case-history. A higher HM (> 15%) was recorded in patients with a history of a cerebrovascular attack, with data on heart failure and in diabetic patients. The majority of patients (39.4% of all who died) died within 24 hours after admission. During the first three days 57% patients died. Analysis of the characteristic of AIM and HM revealed some clinically important data on the HM less than 30% (patients with complicated AIM, with elevated ST segments, with a left ventricular ejection fraction of less than 40% and with and concurrent heart failure). An adverse course of the disease with a high HM (> 30%) was found in patients with complications of AIM. It was highest, more than 60%, in patients after implemented cardiopulmonary resuscitation, in patients with a combination of three markers of imminent shock and patients in shock. The local priority findings on the HM assembled in Slovakia in a non-selected population of patients with AIM confirm that the high HM still persists in patients of advanced age and in women. It is adversely influenced also by some demographic data, educational level, some anamnestic and clinical factors. The HM of patients with AIM may be adversely influenced also by side-effects of protracted economic transformation which is under way. Data assembled in Slovakia are comparable with similar results assembled in other countries.

[The electrocardiogram and thrombolytic therapy in patients with acute myocardial infarct]. / Elektrokardiogram a trombolytická liecba u chorých s akútnym infarktom myokardu.

The objective of the submitted work is to analyze in patients with acute myocardial infarction (AIM) local priority data on ECG markers after admission to hospital, data on some associations of ECG and thrombolytic treatment and to assess in patients with the first AMI data on hospital mortality in connection with some ECG markers. The project was implemented as a prospective multicentre study. An independent audit and collection of data was done in 3123 patients with AIM in 66 departments between Sept. 16 1997 and Sept. 15 1998. The group included patients admitted within 96 hours after development of complaints with the diagnosis or suspicion of AMI who were discharged with the diagnosis of a first/repeated AMI. Elevation of ST segments was recorded in 67.1%, a Q wave in 42.2% and left bundle branch block in 3.7% of the patients. Early diagnosis of AMI based on ECG and data on prolonged stenocardia was made in 55.6% patients. This is the maximal proportion of patients where thrombolytic treatment can be contemplated. Thrombolytic treatment was not administered to 54.9% patients with elevations of the ST segments and in as many as 81.2% patients with left bundle branch block. The hospital mortality in patients with a first AMI is significantly greater in patients with elevations of the ST segment, Q infarction, anterior wall infarction, combined infarction, right ventricular infarction and in patients with bundle branch and fascicular block. It was confirmed that in Slovakia in clinical practice thrombolytic treatment is not always administered consistent with criteria adopted from randomized studies. The result is underutilization or overutilization of thrombolytic treatment to patients with AIM in clinical practice. Underutilization of thrombolytic treatment is generally known. It was demonstrated that attention must be devoted also to overutilization of thrombolytic treatment. All patients where significantly higher hospital mortality was recorded must receive special care already on admission to hospital.

Civilization as a threat to human health?

Civilization can be defined as the distinctly human attributes and attainments of a particular society. In general, the development of civilization is viewed as a positive step for the well-being of the human species, leading to an increased duration and quality of human life. The accelerated progress of civilization (mainly industrialization, urbanization and nutrition) has lead to new possibilities for adverse effects on human health. A collection of problems referred to as 'civilization diseases' has become the subject of serious concern but review of available data indicates that this concept appears to add very little to our understanding of modern environmental influences on human health. Important limitations in the continued use of this term are its non-specificity, the lack of a unifying scientific foundation, and provision of virtually no direction for remediation of these diseases or for future research. In addition, the use of this term has been localized to primarily post-socialist European countries. In view of these limitations, it seems more productive for scientists, in all parts of the world, to embrace the discipline of environmental health science and to discontinue use of the term "civilization diseases".

[Hospitalization of discharged patients with acute myocardial infarction in the thrombolytic era]. / Hospitalizácia prepustených chorých s akútnym infarktom myokardu v trombolytickej ére.

The objective of the work is to assess in discharged patients with AIM data on the period of hospitalization in the intensive care unit and the total period of hospitalization and how these were influenced by stratification into patients with complicated and uncomplicated AIM and patients with a low, medium and high risk. Data on hospitalization were analyzed in 2,527 discharged patients with AIM. The median of hospitalization at intensive care units was 5 days and the mean period of hospitalization 6.35 days. The significantly longer hospitalization (p < 0.001) in patients with complicated AIM (median 6 days) as compared with patients with uncomplicated AIM (median 5 days) impliesonly a one-day longer hospitalization in patients with complicated AIM. The median of total hospitalization was 17 days and the mean period of hospitalization 17.95 days. In the majority of patients the period of hospitalization was 15 - 21 days. More than 20% are hospitalized for more than 21 days. A significant difference of the total period of hospitalization in high risk patients and patients with a medium and low risk expressed in medians is only 2 days. The majority of patients in all three sub-groups of patients with AIM is dicharged between the 15th to 21st day of hospitalization. In the period of hospitalization at intensive care units and total hospitalizatiob of different sub-groups there is no substantial difference in their health status, incl. the danger of sudden cardiac death. By reducing the total period of hospitalization in discharged patients without complications it would be possible to save a considerable percentage of costs of hospitalization. The period of hospitalization must be fixed individually in every patient. In early dicharges it is important to consider also the psychosocial impact of discharge on the patient and his relatives.

[The prehospital phase in patients with acute myocardial infarct in Slovakia. A challenge]. / Predhospitalizacná fáza u chorých s akútnym infarktom myokardu na Slovensku. Výzva na akciu.

Better management of patients with acute myocardial infarction during the prehospital phase is at present a challenge not only for health workers but for society as a whole. The authors pay attention to knowledge of the complex problem of the prehospital phase in patients with acute myocardial infarction which is a prerequisite for finding possible solutions for a favourable effect on their management. The authors analyzed 3,040 patients who were admitted to hospital alive within 96 hours after the development of complaints with suspicion of a first or repeated acute myocardial infarction. They focused attention in particular on prehospital time delay. They found that within a satisfactory time interval (within 2 hours) 29.8% patients were delivered and within a yet acceptable interval of 4 hours 51.6% patients (with respect to effectiveness of thrombolytic treatment). Similarly undesirable are also data on the patient time delay. Within the optimal first hour after development of complaints following the decision of the patient (subjects present) to ask for or seek medical assistance was the decision of 34% patients, during the first two hours 47.5% and within 4 hours 61.2% patients with acute myocardial infarction. The ratio of time delay of the patient in the total prehospital delay is 45.5% even in patients who were admitted during the first hour after development of acute myocardial infarction. In patients who were admitted 4 hours after development of complaints it is 79.5%. The patient is admitted to hospital most quickly if he calls the medical emergency service and latest when he decides to see a doctor. Physicians and other health workers contributed only in 16.4-20.9% patients with acute myocardial infarction to their early decision to seek medical assistance. Patients with an early decision (within one hour) call most frequently the medical emergency service and are taken to hospital by this service. The time delay due to transport is shortest in these patients. The late hospital admission of patients with acute myocardial infarction in Slovakia calls for reduction of the time interval from the development of complaints to hospital admission (total prehospital delay), in particular the time taken by the patient to make up his mind (patient time delay). Early calling of the emergency medical service and transport of the maximum possible number of patients with acute myocardial infarction to hospital by the emergency medical service will greatly improve the management of patients with acute myocardial infarction. Comprehensive implementation of the survival chain (24), the most comprehensive implementation of recommendations of the European Society of Cardiology and the European Resuscitation Council for in the management of patients with acute heart attacks during the prehospital phase (21) and early effective treatment which begins already in the prehospital phase has a favourable impact on the condition of patients with acute myocardial infarction and on their prognosis. Along with early and effective treatment of patients with acute myocardial infarction in hospital and their stratification these are the most important approaches to the development and control of sudden cardiac death. Knowledge of the complex problem of the prehospital phase in patients with acute myocardial infarction is the prerequisite for the elaboration of high standard prehospital management of patients with acute myocardial infarction.

Direct high-performance liquid chromatographic determination of (R)- and (S)-propranolol in rat microdialysate using on-line column switching procedures.

Two different column-switching HPLC systems (CSWs), employing restricted access material for initial pretreatment of biological samples, were developed for the determination of propranolol enantiomers in microdialysate. CSW 1 was a single-pump set-up based on an initial sample clean-up step with a RP-18 ADS precolumn coupled with an ovomucoid analytical column for direct drug enantioseparation. For the two-pump column set-up (CSW 2), a teicoplanin analytical column was applied for the enantioselective assay after initial sample pretreatment using a RP-8 ADS precolumn. The inter-day precision of the CSW 1 ranged from 0.5 to 5.1% for (R)-propranolol and from 5.1 to 10.5% for (S)-propranolol. The limit of detection (LOD) was set at 10 ng/ml and 15 ng/ml for (R)- and (S)-propranolol, respectively. Inter-day relative standard deviation values of the CSW 2 ranged from 1.1 to 9.9% for (R)-propranolol and from 1.3 to 9.6% for (S)-propranolol. The LOD of the method was 3.0 ng/ml for (R)-propranolol and 2.5 ng/ml for (S)-propranolol. Both approaches were successfully applied for stereoselective monitoring of unbound propranolol levels in rat microdialysates.

[Liver steatosis and disorders of mitochondrial oxidative phosphorylation after experimental administration of simazine]. / Steatóza pecene a poruchy oxidacnej fosforylácie mitochondrií po aplikácii simazínu v experimente.

BACKGROUND: Triazine herbicides are widely used in extensive agricultural production, however, some ecological and health hazards occur due to water and food contamination. AIM: The aim of this study was to evaluate the effects of long-term simazine feeding on the steatosis development and the changes of liver bioenergetics in experimental animals. METHODS: A population of B6C3F1 mice were fed with simazine (2 g and 4 g/kg/day, respectively) for 35 weeks. The concentration of cholesterol and triacylglycerols were measured in liver tissue. Liver mitochondria were isolated and parameters of oxidative phosphorylation were assessed polarographically using Clark oxygen electrode with NAD glutamate and/or FAD succinate as substrates. RESULTS: Significant changes (p < 0.001) expressed as medians (with confidence intervals) against control animals were found in both experimental groups after simazine feeding. The concentration of triacylglycerols increased from 10.3 (8.8-10.9) to 20.1 (18.0-20.9) and 47.7 (23.8-56.0), respectively. The parameters of oxidative phosphorylation with NAD substrate glutamate decreased as follows: The index of respiratory control from 7.7 (6.4-9.0) to 4.8 (4.0-6.3) resp. 4.4 (3.9-4.6); the rate of oxygen consumption in the state 3 (with ADP) from 84.2 (82.0-92.3) to 65.4 (50.8-70.7) resp. 69.9 (65.0-78.4) nAtO.mg.prot-1.min-1; and phosporylation rate from 215.3 (204.4-232.2) to 166.3 (120.4-193.6) resp. 169.6 (155.3-176.9) nmolATP.mg.prot-1.min-1. Comparable changes were detected in oxidative phosphorylation with FAD succinate as substrate. CONCLUSIONS: Liver steatosis development and mitochondrial energetics inhibition were determined in mice after long-term simazine feeding, nevertheless, liver energy production was sufficient to satisfy the liver function and the needs of the whole organism. (Tab. 4, Fig. 6, Ref. 24.)