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Inductively coupled plasma-mass spectrometry (ICP-MS) was used to determine the concentrations of 32 elements in the human liver and kidney and 20 elements in the bone, obtained from 70 autopsied dead individuals (54 males, 16 females) between 18 and 76 yr of age from the North Bohemia territory of the Czech Republic. Geometric means, median, minimal-maximal range, as well as distribution and correlation analysis were calculated. Some significant differences among tissue concentrations of trace elements of the women and men were found. In the liver, medians of the concentrations of some elements were higher for men than that for women (Al: 770 vs 610 microg/kg; As: 42 vs 27 microg/kg; Cd: 1800 vs 1390 microg/kg; Rb: 3955 vs 3210 microg/kg; V: 160 vs 105 microg/kg). On the contrary, the content of other elements for men was lower (Bi: 0.8 vs 3.2 microg/kg; Cr: 57 vs 72 microg/kg; Hg: 228 vs 325 microg/kg; Zn: 57.1 vs 68.5 mg/kg). In the kidney of men, there were higher contents of Al (360 vs 245 microg/kg) and Hg (135 vs 75 microg/kg) and lower contents of Zn (47.7 vs 59.7 mg/kg) and I (135 vs 220 microg/kg) than those of women. In the case of bone, the concentrations of Cu and Rb were higher for men (1410 microg Cu/kg and 405 microg Rb/kg, respectively) than for women (655 microg Cu/kg and 285 microg Rb/kg, respectively). On the contrary, the content of Mn was considerably lower for men (110 microg Mn/kg) than for women (215 microg Mn/kg).

BACKGROUND: Metoprolol can improve haemodynamics in chronic heart failure, but survival benefit has not been proven. We investigated whether metoprolol controlled release/extended release (CR/XL) once daily, in addition to standard therapy, would lower mortality in patients with decreased ejection fraction and symptoms of heart failure. METHODS: We enrolled 3991 patients with chronic heart failure in New York Heart Association (NYHA) functional class II-IV and with ejection fraction of 0.40 or less, stabilised with optimum standard therapy, in a double-blind randomised controlled study. Randomisation was preceded by a 2-week single-blind placebo run-in period. 1990 patients were randomly assigned metoprolol CR/XL 12.5 mg (NYHA III-IV) or 25.0 mg once daily (NYHA II) and 2001 were assigned placebo. The target dose was 200 mg once daily and doses were up-titrated over 8 weeks. Our primary endpoint was all-cause mortality, analysed by intention to treat. FINDINGS: The study was stopped early on the recommendation of the independent safety committee. Mean follow-up time was 1 year. All-cause mortality was lower in the metoprolol CR/XL group than in the placebo group (145 [7.2%, per patient-year of follow-up]) vs 217 deaths [11.0%], relative risk 0.66 [95% CI 0.53-0.81]; p=0.00009 or adjusted for interim analyses p=0.0062). There were fewer sudden deaths in the metoprolol CR/XL group than in the placebo group (79 vs 132, 0.59 [0.45-0.78]; p=0.0002) and deaths from worsening heart failure (30 vs 58, 0.51 [0.33-0.79]; p=0.0023). INTERPRETATION: Metoprolol CR/XL once daily in addition to optimum standard therapy improved survival. The drug was well tolerated.

Variations in the levels of Cu, Se and Zn in blood were analyzed in relation to gender, age, BMI, smoking and hormonal contraception. The blood samples were collected from 3,207 blood donors (2,362 men, 845 women) during years 1996-2003. Blood concentrations of these elements were in the same range as those found for populations of other European countries. Significant differences exist between men and women, in blood concentration, for Cu (840 microg Cu.l(-1) vs. 970 microg Cu.l(-1), p0.01) and Zn (6,780 microg Zn.l(-1) vs. 6,235 microg Zn.l(-1), p0.01) only. The level of Cu in relation to age is increasing in men, but decreasing in women. The level of Se in relation to age increases regardless of sex. Concentrations of Zn rise with age in women group, only. Positive correlation was found between BMI and level of Cu only for group of men. For Se levels and BMI differences exist only in men namely between groups20 and35 (82 microg Se.l(-1) vs. 92 microg Se.l(-1)). Slight positive correlations exist between Zn concentration and BMI in women only. The significant differences were found between smokers and non-smokers for Cu in men (850 microg Cu.l(-1) vs. 830 microg Cu.l(-1)) and Se (81 microg Se.l(-1) vs. 84 microg Se.l(-1)). The smoking has not significant influence on concentration of Zn in the blood. The hormonal contraception significantly increases the concentration of Cu in blood (920 microg Cu.l(-1) vs. 1,270 microg Cu.l(-1), p0.01). The levels of Se and Zn in blood are not influenced using hormonal contraception.

Mutagenic activity of extractable organic matter (EOM), from airborne particles collected over winters in four towns of Czech Republic, was investigated by the means of Salmonella typhimurium indicator strains TA98 and YG1041 using the Ames plate incorporation assay. Mutagenicity of all tested samples showed significant dose-related increase in number of revertants per mg of EOM. The direct mutagenic potency detected with TA98 increased further in the presence of external metabolic activation. The mutagenic potency detected with YG1041 was about two orders of magnitude higher than that detected with TA98. The mutagenicity results correlated with the concentrations of the polycyclic aromatic hydrocarbons (PAHs) determined by GC/MS. Local differences in mutagenicity, expressed as numbers of revertants per m3 of air, were observed with the highest values in Prague air samples. For routine ambient air mutagenicity monitoring, the use of YG1041 and the plate incorporation test are recommendable.

The retrospective study evolution of trends in concentrations of Cd, Pb, Cu and Se in the population of the Czech Republic over 30 years period could be useful in design of regulations concerning health protection, prevention of diseases caused by deficiency of trace elements and have considerable economic importance. Concentrations of the named elements in the serum were determined by means of atomic absorption spectrometry (AAS) after mineralisation in a microwave digestion system. The 1433 samples of serum (730 males and 703 females, average age 48.7 and 49.1 years respectively) from a time period 1970-1995 were obtained from the Serum bank of National Institute of Public Health and volunteers (1999). Serum samples from the years 1970, 1975, 1980, 1985, 1990, 1995 and 1999 were examined. The accuracy of the results was checked by means of the Control material Seronorm Whole Blood 404,107 and Seronorm Serum 704,121, Nycomed. The concentration of Cd had a decreasing trend for the years 1975-1999 (0.82 microgram Cd.l-1 vs 0.47 microgram Cd.l-1). The levels of Pb are falling in the interval 1970-1980 (15.6 micrograms Pb.l-1 vs. 6.6 micrograms Pb.l-1). In year 1985 concentration of Pb increased (10.7 micrograms Pb.l-1) but subsequently decreased again (1995--6.4 micrograms Pb.l-1). In year 1999, it was 8.9 micrograms.l-1. The concentration of Cu decreased in period 1970-1990 (1525 micrograms Cu.l-1 vs. 990 micrograms Cu.l-1). From 1990 to 1999 the levels of Cu had an increasing tendency (1999--1060 micrograms Cu.l-1). Levels of Se in the interval 1970-1985 were surprisingly equal (58.1 micrograms Se.l(-1)-54.4 micrograms Se.l-1). However in the interval 1986-1990 the level of Se sharp declined (38.3 micrograms Se.l-1). Since 1990 levels of Se in serum increased again, up to 67.1 micrograms Se.l-1 in 1999. Statistically significant differences between men and women were found only in Cu and Pb concentrations. Concentrations of under study elements corresponded to the published values concerning unexposed population.

This study aimed at determining blood concentrations of lead (B-Pb) and cadmium (B-Cd) in a group of 1215 healthy blood donors (895 males, 320 females) and 758 children (397 boys, 361 girls) aged 10 years, sampled in 1996-1998 in four districts of the Czech Republic. The analysis was performed using atomic absorption spectrometry. The median B-Pb values were lower in children (34 mg/L) than in adults. In the group of adults, the level was significantly higher in men (46 mg/L) than in women (29 mg/L). In none of the groups the 90th percentile exceeded the value of 100 mg/L. The B-Cd values in adults depended on smoking habit (median non-smokers: 0.5 mg/L, male smokers--1.2 mg/L, female smokers--1.0 mg/L). In children, more than 50% of values were under the limit of detection. The obtained values were used to propose reference values for the Czech population.

The estimation of the copper saturation pathways of the Czech urban population is presented. The data on copper concentrations proceed from the System of monitoring the environmental impact on population health in the Czech Republic in the period 1994-1998. The copper concentrations were monitored in foodstuffs from the commercial network, in drinking water at the outlets of the waterworks and in the public water main networks, and in the ambient air. The copper levels were measured also in biological material to obtain the data on the copper saturation of the population under monitoring. The copper intake from foodstuffs and drinking water did not vary significantly either in the particular years of monitoring or individual cities. The same concerns also the copper levels in biological material. The total copper intake for an average adult was estimated to be 20.2 micrograms/kg b.w./d., i.e. 1300 micrograms/d. Over 99% of the total intake was that from the diet. The exposure from the intake of drinking water as well as from ambient air was low. The total daily intake lies in the interval 1000-2000 micrograms/d which is usually found in the similar studies of the copper intake. It represents only 40% of the daily dietary copper intake recommended by the JECFA FAO/WHO Commission, 1982. The copper levels in biological material did not differ from the reference values, and did not indicate any evincible hyposaturation of the population with copper.

Knowledge of normal levels of concentrations of trace elements (Cd, Pb, Hg, Cu, Zn, and Se) in the population serves, among others, in design of regulations concerning health protection, determination of exposure limits and prevention of diseases caused by deficiency of trace elements. Concentrations of the named elements in whole blood of the Czech population were determined by means of atomic absorption spectrometry. The blood was collected during 1996-1998 from 1,216 blood donors (896 males and 320 females, average age 33 years) and 758 children (397 boys and 361 girls, average age 9.9 years). Mineralisation in a microwave digestion system was used in sample preparation. The accuracy of results was checked by means of the Control material Seronorm Whole Blood 404107 and Seronorm Serum 704121, Nycomed. Values of concentrations of the trace elements in blood found for adult (medians) were 0.7 microgram Cd.l-1, 800 micrograms Cu.l-1, 0.78 microgram Hg.l-1, 41 micrograms Pb.l-1, 76 micrograms Se.l-1, and 5,800 micrograms Zn.l-1, respectively. Statistically significant differences between men and women have been found in the concentrations of Cu, Hg, Pb, and Zn. In the juvenile population following medians of concentrations have been found: 0.15 microgram Cd.l-1, 1,047 micrograms Cu.l-1, 0.46 microgram Hg.l-1, 34 micrograms Pb.l-1, 69 micrograms Se.l-1, and 8,180 micrograms Zn.l-1. Statistically significant differences between boys and girls were found only in Pb and Zn concentrations. Concentrations of the studied elements correspond to the published values concerning population not exposed professionally.

The new calcium antagonist, the dihydropyridine derivative isradipine (Lomir, Sandoz) is used above all in the treatment of hypertension. During oesophageal stimulation the authors proved its very favourable effect also in patients with coronary insufficiency during exertion. A single oral dose of 7.5 mg of isradipine led in all 14 examined patients to increased tolerance of exertion; in 36% of the patients after administration of the drug coronary insufficiency was no longer found. In the remaining patients the incidence of coronary insufficiency was shifted to higher frequencies. The authors recorded a drop of systolic and diastolic pressure during exertion, during rest as well as during recovery. No undesirable effects nor hypertension were present. The drug is a useful preparation in particular in hypertonic patients with angina on exertion.

The risk of possible complications in atrial flutter leads to attempts to use all available therapeutic possibilities to eliminate this disorder of the cardiac rhythm. By oesophageal stimulation the sinus rhythm was restored in 40% and a change to atrial fibrillation was achieved in 50% of the patients. The advantages of this method include above all speed and the minimal risk of complications; the disadvantage of the method is the unpleasant sensation when the electrode is inserted and the painful perception of the stimuli. Oesophageal stimulation can be recommended as the method of choice in treatment of atrial flutter.

Electrophysiological effects of oral isradipine were studied. There are controversial references about the presence of its selective negative chronotropic influence from in vitro and in vivo studies using intravenous route. The authors administered 7.5 mg and 2.5 mg of isradipine orally in two groups of patients. Electrophysiological parameters were measured by use of the transoesophageal atrial pacing prior to the administration and 120 minutes after it. Significant fall in blood pressure was observed in both groups. Changes of atrioventricular nodal parameters such as stimulus-R interval. Wenckenbach point and probable effective refractory period of atrioventricular node showed positive dromotropic effect on artioventricular conduction, but the negative chronotropic action was not proved. On the contrary, the mean sinus cycle length shortened significantly in both groups and the maximal sinus node recovery time decreased after isradipine. The extent of changes of both sinus and atrioventricular nodal parameters is similar and is not consistent with selective effect of isradipine on sinus node.

Using invasive electrophysiological methods, the authors evaluated the preparation Diltiazem VUFB tablets on parametres of sinus automaticity in the "sick sinus syndrome" and on properties of the atria. They confirmed significant inhibition of automaticity which is not signalized by a corresponding decrease of the nodal frequency, and may remain concealed and lead unexpectedly to disorders of the cardiac rhythm. This is not a specific property of the preparation, a similar action on the sick sinus is exerted by all calcium antagonists with clinically confirmed effects on the conduction system. Diltiazem is already produced in this country and sold on the market with the name of Discordin SPOFA tablets.

The incidence, circumstances, and mechanism of development of cardiac arrest in 786 patients with myocardial infarction treated at a coronary care unit within a five-year period were studied and clinical factors are analysed with respect to success of resuscitation. One or more episodes of cardiac arrest occurred in a total of 156 patients (19.8%). Of these, 25 (16.0%) were successfully resuscitated and 131 (84.0%) died. At the clinical ward where the patients had been transferred after the acute stage, cardiac arrest occurred in additional 22 patients, of whom two were successfully resuscitated. Thus, the total number of successfully resuscitated patients throughout the five-year period was twenty-seven. The results of resuscitation were poorer in elderly patients, in those with anterior infarction, and above all in patients with severe symptoms of mechanical heart failure. Anamnestic factors (chronic angina pectoris, previous myocardial infarction, hypertension, diabetes mellitus, ischaemic disease of the lower limbs) were not significantly associated with the results of resuscitation. Primary ventricular fibrillation was the principal mechanism of cardiac arrest in 24 of the 27 patients successfully resuscitated, and its total incidence in the investigated group was 3%. The prognosis of resuscitation in patients with primary ventricular fibrillation was very good, and in all of them the resuscitation was successful and permanent.

The authors investigated the action of a single oral dose of the recently developed preparation Diltiazem VUFB tabl. on electrophysiological parameters of atrioventricular conduction - the AH, HV interval, Wenkebach's point and the relative, functional and effective refractory period of the atrioventricular node. The preparation affects significantly parameters of the level of the node and its effect is comparable with data on the action of diltiazem produced abroad.

Mortality during the hospitalization period was analyzed in a sample of 786 patients with acute myocardial infarction [AMI], admitted to the coronary care unit within a five-year period from a catchment area of 200 000 urban inhabitants. The total mortality during the hospitalization period amounted to 19.2%. The prognostic significance of certain clinically meaningful phenomena was appraised on the basis of their association to the mortality. It was demonstrated that the factors decisive for the prognosis of a patient with AMI are age, previous myocardial infarction, extent and localization of the ischaemic lesion apparent from the ECG tracing, and, in addition, presence of the atrioventricular and intraventricular conduction defects, especially if combined with anterior myocardial infarction. Patients with a high cumulation of these prognostic factors exhibited severe signs of mechanical heart failure, which is the mechanism of death in practically all of the deceased patients under the present possibilities of treatment.