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Biomedical subjects

O Mayer

Publications and source records attributed to O Mayer.

At least 19 recordsLinked to original sources

Mild hyperhomocysteinaemia is associated with increased aortic stiffness in general population.

Total homocysteine (tHcy) level was identified as a strong and independent predictor of cardiovascular events. We investigated the association between tHcy and mechanical properties of large arteries in a random, general population-based sample of 251 subjects (mean age 48 years). Large artery properties, such as aortic and peripheral (lower-limb) pulse wave velocity (PWV), and augmentation index of radial artery were measured using semi-automatic Sphygmocor device. Aortic PWV (APWV) positively correlated with tHcy (r = 0.28, P<0.0001), and a significant increasing trend of APWV was found by tHcy quartiles (P = 0.0003 by ANOVA). This association remained significant after adjustment for conventional cardiovascular risk factors (age, gender, smoking, overweight, hypertension, dyslipidaemia and impaired glucose metabolism) and for usual homocysteine confounders (folate, B12, renal function). Subjects with mild hyperhomocysteinaemia (i.e. with tHcy > or = 15 micromol/l) had 2.74 times higher risk of having their APWV over 8.42 m/s (i.e. in the top quartile). No such association was found either for PWV measured at lower extremity or for radial augmentation index. In conclusion, in our series of subjects from general population, we found a strong and independent relationship between homocysteine concentration and APWV, a parameter of stiffness of central arteries.

Adult↗

Folate co-administration improves the effectiveness of fenofibrate to decrease the lipoprotein oxidation and endothelial dysfunction surrogates.

Fibrate therapy results in elevation of plasma total homocysteine (tHcy), which is known to induce oxidative stress and endothelial dysfunction. We aimed to establish whether fibrate-induced elevation of tHcy has also similar consequences and whether they may be prevented by folate co-administration. Eighteen subjects with hypercholesterolemia were included in an open, prospective, cross-over study. We compared intra-individually the effect of fenofibrate on tHcy, oxidative stress and endothelial dysfunction surrogates, in monotherapy and when combined with 10 mg of folate. These effects were also compared with fluvastatin monotherapy. Fenofibrate in monotherapy significantly decreased LDL cholesterol, increased the tHcy by 39.5 %, while oxidized LDL (oxLDL), malondialdehyde (MDA), von Willebrand factors (vWf) and thrombomodulin (TMD) remained unchanged. When fibrate was co-administered with folate, the tHcy remained on the initial post-diet level, while both the total and oxLDL as well as MDA, vWf and TMD decreased. In contrast to fenofibrate monotherapy, fluvastatin (80 mg) had a similar effect as combined therapy with fenofibrate and folate, while tHcy remained uninfluenced. In conclusion, fenofibrate decreases the LDL cholesterol, but in contrast to fluvastatin, has no significant antioxidative and endothelium-protective potential, probably due to a concomitant increase of tHcy. These effects may be improved by co-administration of folate.

Adult↗

Assays for the RNA chaperone activity of proteins.

Proteins with RNA chaperone activity promote RNA folding by loosening the structure of misfolded RNAs or by preventing their formation. How these proteins achieve this activity is still unknown, the mechanism is not understood and it is unclear whether this activity is always based on the same mechanism or whether different RNA chaperones use different mechanisms. To address this question, we compare and discuss in this paper a set of assays that have been used to measure RNA chaperone activity. In some assays, this activity is related to the acceleration of monomolecular reactions such as group I intron cis-splicing or anti-termination of transcription. Hereby, it is proposed that the proteins release the RNAs from folding traps, which represent the kinetic barriers during the folding process and involve the loosening of structural elements. In most assays, however, bimolecular reactions are monitored, which include the simple acceleration of annealing of two complementary RNAs, the turnover stimulation of ribozyme cleavage and group I intron trans-splicing. The acceleration of these reactions most probably involves the unfolding of structures that interfere with annealing or folding and may in addition provoke annealing by crowding. Most assays are performed in vitro, where conditions might differ substantially from intracellular conditions, and two assays have been reported that detect RNA chaperone activity in vivo.

Introns↗

[Pilot study of the noninvasive assessment of endothelial dysfunction by post-occlusion dopplerometry velocity curves analysis in arteria brachialis].

BACKGROUND: A new method of noninvasive assessment of endothelial dysfunction was used in this pilot study. Study has been set on a. brachialis dopplerometry velocity curves analysis. Index of blood stream deceleration between the first and second minute of the postocclusion periode was measured on a. brachialis after transient mechanical occlusion of the forearm--so called Deceleration Index. METHODS AND RESULTS: Eighteen patients with so far untreated hypercholesterolemia were involved in our study. Profile of velocity curves became significantly different after six months of fluvastatin therapy, Deceleration Index increased from 3 % to more than 7 % (p<0.05). That correlated with LDL-CH levels decrease, but also with the significant decrease of biochemical markers of endothelial dysfunction (trombomodulin, von Willebrand factor). CONCLUSIONS: The result is corresponding with previously published studies that have proved endothelial function improvement after statin therapy using another ultrasonographic methods.

Anticholesteremic Agents↗

[Recommendations for the treatment of tobacco dependence].

This first Czech version of guidelines formulated by the working group of mentioned medical associations is based on current literature and international guidelines. They are aimed mainly on clinical medicine and on incorporation of this treatment into the health care system according to WHO recommendations. They should serve to the treatment of tobacco dependence at any level: during any contact with the smoking patient (short intervention), in specialised centres or for the health care providers or health system itself.

Humans↗

[Epidemiological study of hypothyroidism as cardiovascular risk in population].

BACKGROUND: Prevalence of hypothyroidism (HT) markedly differs among various populations. We aimed to establish the prevalence of HT in the Czech population and to assess its association with conventional cardiovascular risk factors. METHODS AND RESULTS: 1240 subjects (629 m, 611 f; mean age 52.3); a random, population-based sample were evaluated. Cut-off points for thyroid parameters were defined as follows: thyreostimulating hormone (TSH) 0.58-3.65 mU/I, free thyroxine (fT4) 9-22 pmol/l and thyroid peroxidase antibodies (TPOAb) < or = 14 IU/A. The overall prevalence of HT was 6.8% in males and 13.8% in females (p < 0.0001); subclinical HT (high TSH, normal fT4) was found in 3.0% and 8.0%, overt-untreated (high TSH, low fT4) in 3.2% and 3.0% and overt-treated HT in 0.6% and 2.8% of males and females, respectively. Moreover, in euthyroid subjects, 4.6% of males and 9.3% of females showed positive TPO-Ab (p < 0.0001). The adjusted relative risk of hypothyroidism was significantly increased in males with manifest vascular disease (odds ratio 3.48 (1.56-7.74)]), in females aged > or = 55 years (2.08 (1.29-3.36)) or hypertension (1.80 (1.03-3.13)), and moreover, in males and females with positive TPOAb (5.81 (2.57-13.13) and 5.92 (3.38-10.36), resp.) CONCLUSIONS: Hypothyroidism was found in Czech population highly prevalent and it can contribute to the coronary risk, produced by conventional factors.

Adult↗

[Association between free thyroxin concentration and degree of heart failure in patients with chronic heart insufficiency].

BACKGROUND: It is evident, that overt thyroid dysfunction (both, hypo- or hyperthyroidism) could be associated with heart failure. The aim of our study was to establish whether also mild changes in free thyroxin (fT4) may influence the degree of heart failure in patients with chronic heart insufficiency. METHODS AND RESULTS: There were included 148 patients (m 121, f 27, mean age 63.8 +/- 1.14) with clinical chronic heart failure were, with fT4 levels within the normal range (9-22 pmol/l) and without thyroid suppression or substitution treatment. Degree of heart failure was quantified by plasma B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP) and big endothelin. Patients with fT4 in the range 11.9-14.6 pmol/l (optimal, 3rd-6th decile) had significantly lower NT-proBNP (718 +/- 70.4 pg/ml), than those with fT4 < or = 11.8 (low-normal, bottom two deciles) (1236 +/- 223.6 pg/ml; p < 0.03) and those with fT4 over 14.6 pmol/l [high-normal, top four deciles] (1192 +/- 114.9 pg/ml; p < 0.0002). These differences remain significant also if adjusted for age, gender and other confounders; adjusted odds ratio was 1.30 (1.05-1.59) for optimal vs. low-normal and 1.27 (1.04-1.55) for optimal vs. high-normal. Similar statistical differences were found also in BNP and high endothelin, but only between optimal and high-normal fT4 strata. CONCLUSIONS: The degree of heart failure could be influenced also by mild changes in fT4 concentration.

Chronic Disease↗

Educational level and risk profile of cardiac patients in the EUROASPIRE II substudy.

STUDY OBJECTIVE: To ascertain, whether, conventional risk factors and readiness of coronary patients to modify their behaviour and to comply with recommended medication were associated with education in patients with established coronary heart disease. DESIGN AND METHODS: EUROASPIRE II was a cross sectional survey undertaken in 1999-2000 in 15 European countries to ascertain how effectively recommendations on coronary preventions are being followed in clinical practice. Consecutive patients, men and women </=71 years who had been hospitalised for acute coronary syndrome or revascularisation procedures, were identified retrospectively. Data were collected through a review of medical records, interview, and examination at least six months after hospitalisation. The education reached was ascertained at the interview. MAIN RESULTS: A total of 5556 patients (1319 women) were evaluated. Significantly more patients with ischaemia had only primary education, in contrast with the remaining diagnostic groups. Body mass index and glucose were negatively associated with educational level, while HDL-cholesterol was positively associated. Men with highest education had significantly lower systolic blood pressure and total cholesterol. The prevalence of current smoking decreased significantly from primary to secondary and high education only in men. Both men and women with primary educational level were more often treated with antidiabetics, and antihypertensives, but less often with lipid lowering drugs. The effectiveness of treatment was virtually the same in all education groups. CONCLUSIONS: Patients with higher education had lower global coronary risk, than those with lower education. This should be considered in clinical practice. Particular strategies for risk communication and counselling are needed for those with lower education status.

Adult↗

[Quality of therapeutic control of hyperlipidemias in secondary prevention of coronary heart disease in the light of current recommendations].

Definite evidence has been established, that coronary patients benefit from appropriate therapeutic control of risk profile, as recommended by several Guidelines. However, the impact of these Guidelines on coronary morbidity and mortality is limited by level of its implementation into broad clinical practice and possibility to reach the defined secondary preventive targets with currently available therapeutic resources. We reviewed 6 studies, realized between 1995 and 2000, which was aimed to establish, how many patients with clinical coronary heart disease achieved recommended targets for lipid-lowering treatment. From 10850 cardiac patients examined in these surveys, in average 42.8% were treated with lipid lowering drugs, but only in 26.8% and 24.3% of patients was reached the target level for total and LDL cholesterol, resp. On the other hand use of lipid lowering drugs markedly increased from about 16-32% in 1995, 61-93% in 2000, moreover in the same time period the proportion of patients reaching target levels of total cholesterol increased from about 14-18% to 30-64%.

Coronary Disease↗

Chlamydia pneumoniae IgA seropositivity is associated with increased risk for atherosclerotic vascular disease, myocardial infarction and stroke in dialysis patients.

BACKGROUND: Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in patients with chronic renal failure undergoing dialysis therapy. Aim of the study was to evaluate whether there is a correlation between a past infection with Chlamydia pneumoniae inducing antibody production and the manifestation of symptomatic atherosclerotic disease in patients with chronic renal failure on hemodialysis. METHODS: A retrospective study was designed including 151 dialysis patients with a clinical apparent atherosclerotic disease (case subjects) and 116 dialysis patients without any symptomatic atherosclerotic manifestation (control group). An ELISA was used to measure seropositivity for IgA and IgG titers. RESULTS: Elevated IgA titers against Chlamydia pneumoniae were found in 67% of the case subjects, but only in 29% of the controls (OR 5.34, CI 2.98-9.56). Forty-five patients of the case subjects had a history of myocardial infarction (OR 5.14, CI 2.38-11.09). Prior stroke was found in 30 patients in case subjects (OR 4.37, CI 1.73-11.01). The follow-up after 3 years showed that only 20 patients died from cardiovascular disease in the control group in comparison to 57 patients in the case group (OR 2.51). IgG seropositivity revealed an OR of 1.02 (CI 1.0-2.1). CONCLUSION: These results indicate that IgA seropositivity is associated with an increased frequency of symptomatic atherosclerotic manifestations. Especially an increased number of patients was found with prior myocardial infarction or stroke when elevated IgA titers were detected. IgA positivity seems to be a separate prospective risk factor in patients with chronic renal failure and hemodialysis for premature cardiovascular death.

Aged↗

[D-dimers in the diagnosis of deep venous thrombosis].

D-dimers (D-d) are degeneration products of fibrin. According to some recommendations (Lee et al., Ann Rev Med, 2002; 53: 15-33) the vein thromboembolism may be excluded by the determination of D-dimers level especially when the probability of diagnosis of deep vein thrombosis is less strong. The determination of D-dimers with made possible was the development of monoclonal antibodies and their detection is based on the determination using the principle of ELISA or agglutination techniques. An increased D-d level is not completely specific for venous thrombo-embolism; it may be enhanced during tumorous diseases, infections, kidney failure etc. In contrast, a negative result of the test is highly sensitive for exclusion of deep vein thrombosis or pulmonary embolism (sensitivity 90% to 100%). The authors also present their own results of a prospective study on the dynamism of D-dimer level in plasma of patients with deep vein thrombosis demonstrated by sonography at the time of start and in the course of the anticoagulant therapy. D-dimers were determined by two methods, the quantitative agglutination latex method and the rapid VIDAS ELISA method. At the time of admission, an increased level was established in up to 80% of patients using the VIDAS method and in 70% using the latex method. In the period of five to seven days after the beginning of treatment the proportions were 75% and 60%, respectively, according to the method used. After six weeks, a slightly elevated level above normal may be expected in 1/3 of patients and less than in 1/5 of patients in the later months.

Biomarkers↗

Folding of the td pre-RNA with the help of the RNA chaperone StpA.

The td group I intron is inserted in the reading frame of the thymidylate synthase gene, which is mainly devoid of structural elements. In vivo, translation of the pre-mRNA is required for efficient folding of the intron into its splicing-competent structure. The ribosome probably resolves exon-intron interactions that interfere with splicing. Uncoupling splicing from translation, by introducing a non-sense codon into the upstream exon, reduces the splicing efficiency of the mutant pre-mRNA. Alternatively to the ribosome, co-expression of genes that encode proteins with RNA chaperone activity promote folding of the td pre-mRNA in vivo. These proteins also efficiently accelerate folding of the td pre-mRNA in vitro. In order to understand the mechanism of action of RNA chaperones, we probed the impact of the RNA chaperone StpA on the structure of the td intron in vivo and compared it with that of the well characterized Cyt-18 protein, which is a group-I-intron-specific splicing factor. We found that the two proteins have opposite effects on the structure of the td intron. While StpA loosens the three-dimensional structure, Cyt-18 tightens it up. Furthermore, mutations that destabilize the intron structure render the mutants sensitive to StpA, whereas splicing of these mutants is rescued by Cyt-18. Our results provide direct evidence for protein-induced conformational changes within a catalytic RNA in vivo. Whereas StpA resolves tertiary contacts enabling the RNA to refold, Cyt-18 contributes to the stabilization of the native three-dimensional structure.

Base Sequence↗

Unexpected inverse relationship between insulin resistance and serum homocysteine in healthy subjects.

Mild hyperhomocysteinemia has been established as a new independent risk factor for atherosclerosis and thrombosis. The metabolic syndrome of insulin resistance is associated with a high risk of coronary heart disease. Our objective was to determine if any relationship exists between the metabolic syndrome of insulin resistance in non-diabetic subjects and total serum homocysteine levels. Sixty-six healthy volunteers (33 males and 33 females) were selected from the population of Pilsen. Insulin resistance was measured by the Insulin Suppression Test using Octreotide. Steady-state plasma glucose concentrations at the end of the test period provided a quantitative measure of insulin resistance. Serum homocysteine level was estimated by high-pressure liquid chromatography. Serum folate and vitamin B12 were estimated using commercial kits on an Abbott IMx analyzer. All other laboratory tests were performed by standard methods in a routine biochemical laboratory. Subjects with the highest tertile of steady-state plasma glucose showed a significantly higher body mass index, blood pressure, fasting plasma triglyceride levels, plasminogen activator inhibitor-1 and lower HDL-cholesterol, i.e. an insulin resistance pattern. These subjects had significantly lower serum homocysteine levels compared with non-insulin resistant subjects. The negative association of insulin resistance and serum homocysteine was unexpected. The contribution of plasma folate levels to serum homocysteine levels and serum creatinine was significantly negative and positive, respectively.

Age Factors↗

The pursuit of secondary prevention targets in Czech coronary patients. A comparison of EuroAspire I and II surveys.

BACKGROUND: Definite evidence has been established, that coronary patients benefit from appropriate secondary prevention measures, as recommended by the European and National Guidelines. EuroAspire I (1995) and EuroAspire II (1999) were surveys aimed to evaluate the state of the implementation of guidelines into the every-day medical practice in several European countries, including Czech Republic. We wondered to what extent the practice in secondary prevention of Czech physicians, since the guidelines were published, changed during 5 years, to pursue the targets. METHODS: We compared two surveys, undertaken in the same geographical areas of the Czech Republic. Consecutive patients, males and females, less than 71 years of age were indentified following acute coronary event or revascularisation procedure and were interviewed and examined at least 6 months after hospitalization. RESULTS: The Czech surveys included 331 patients in EuroAspire I and 410 in EuroAspire II. In EuroAspire II, the total number of smokers decreased in males, but increased in females. The patients were more obese, had higher glucose levels as well, while blood pressure, total and LDL cholesterol and triacylglycerols were lower, than in EuroAspire I. Corresponding changes also occurred in the prevalence of hypertension and hyperlipidaemias by definitions. There was a significant increase in the use of betablockers, ACE inhibitors and hypolipidemic drugs, mainly statins. In conclusion, in spite that the compliance with the recommendations for secondary prevention improved, achievement of targets remained rather unsatisfactory, likewise in other European countries.

Chi-Square Distribution↗

A population study of the influence of beer consumption on folate and homocysteine concentrations.

OBJECTIVE: Mild hyperhomocysteinemia is a significant and independent risk factor for vascular diseases. Blood total homocysteine concentration (tHcy) is considered to be the product of an interaction between genetic and nutritional factors notably intake of folate, vitamin B12 and pyridoxine. The aim of the study was to determine whether regular intake of beer containing large amount of folate and other vitamins influences the tHcy blood concentrations. DESIGN: Cross-sectional population-based survey. SETTING: Adult population, residents of Pilsen (Czech Republic) and vicinity. SUBJECTS: Population series included 292 males and 251 females aged 35-65 y, mean age 53.4 y. All subjects were examined by a standard protocol for clinical, anthropometrical and laboratory estimations. MAIN OUTCOME MEASURES: tHcy was measured by high-pressure liquid chromatography with fluorescent detection, blood folate and B12 levels immunochemically using commercial kits. RESULTS: Beer intake was associated with blood folate and vitamin B12 concentrations positively and with tHcy concentration negatively. By categories of beer intake, subjects with intake of 1 l daily or more had significantly lower tHcy and higher folate concentrations than those reporting lower daily beer intake. CONCLUSION: Moderate beer consumption may help to maintain the tHcy levels in the normal range due to high folate content. Folate from beer may thus contribute to the protective effect of alcohol consumption on cardiovascular disease in population with generally low folate intake from other nutrients. SPONSORSHIP: Supported by grant 301/00/P089 Grant Agency of Czech Republic and Internal Grant Agency of the Ministry of Health.

Adult↗

[Changes in the risk profile and the development of hypertension in the population of Plzen 1987-1989 and 1995-1996].

OBJECTIVE: To evaluate risk factors and the general risk profile in a longitudinally followed-up cohort of the Plzen population. MATERIAL AND METHODS: The investigation was made in a cohort of 332 men and 280 women selected from the epidemiological study PILS II (Plzen longitudinal study) examined in 1987-1989 and 1995-1995. Both investigations adhered to the standard protocol. Anamnestic data were assessed, anthropometric parameters (BMI). Blood pressure (BP) was assessed by means of a mercury sphygmomanometer using the standard procedure, biochemical parameters were examined from a blood sample on fasting in the routine laboratories of the Faculty Hospital Plzen. Changes of individual factors were evaluated by the paired Wilcoxon test and chi 2 group test resp. The global coronary risk was calculated by means of logistic coefficients from the Framingham study. RESULTS: In the cohort which aged on average by 7.6 years the number of smokers decreased in men by 8.1% and by 3.6% in women. The blood pressure increased significantly in both sexes, there was an increase in the number of hypertensive subjects by 26.8% in men and 21.7% in women. In men there was a significant decrease of non-HDL cholesterol, in women, there was a significant increase of subjects with diabetic dyslipidaemia. The total coronary risk (Framingham score) increased after standard transposition to the age of 60 years only by 0.5% in men and women, which reflects the risk due to increased BP. The standard of treatment of hypertension was quite unsatisfactory. When using criteria SBP > or = 140 and/or DBP > or = 90 mm Hg during the second examination 71% of the patients remained without treatment. The number of subjects not aware of hypertension declined from 54% to 19.3% of subjects. A favourable indicator was the finding that there was a decline of hypertensive subjects with a high coronary risk (> or = 20% from ca 11 to 6%). CONCLUSION: During the investigation period in the cohort which to a certain extent represents the Plzen population a certain improvement of the risk profile occurred in particular as regards smoking and disorders of the lipid spectrum, however not as regards the prevalence and treatment of hypertension. Despite the favourable development in the Czech population in the investigated cohort, obviously at the expense of poor control of hypertension, the average coronary risk did not improve.

Adult↗

[Statins in the treatment of patients with arterial occlusive disease of the lower extremities].

In patients with advanced atherosclerosis manifested by arterial occlusion in the lower extremities without a baseline blood lipid disorder statin treatment caused improvement of the efficiency, i.e. prolongation of the claudication interval, while in a comparable control group without statins the efficiency deteriorated further. In patients with arterial occlusion of the lower extremities with baseline dyslipidaemia statin treatment proved protective, i.e. at least it retarded the patients' complaints. The authors recorded improvement of the prooxidation state which followed after the dynamics of improvement of the impaired blood lipid spectrum. The results admit a possible part played by the pleiotropic effect of statins.

Adult↗