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Biomedical subjects

O Mayer

Publications and source records attributed to O Mayer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Insulin-mediated glucose disposal is decreased in normal subjects with relatively low plasma magnesium concentrations.

The relationship between the plasma magnesium (Mg) concentration and steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations at the end of a 180-minute infusion of octreotide, insulin, and glucose was determined in 98 healthy nondiabetic subjects. For the purposes of data analysis, the population was divided into tertiles on the basis of the plasma Mg concentration: I, plasma Mg 0.83 mmol/L; II, plasma Mg 0.84 to 0.91 mmol/L; and III, plasma Mg 0.92 mmol/L. The three groups were identical in terms of age, gender distribution, and degree of obesity. However, both fasting plasma insulin (P < .05) and SSPG (P < .05) concentrations were significantly higher in the tertile (I) with the lowest plasma Mg concentration. Furthermore, there was a significant inverse correlation between plasma Mg and SSPG concentrations (r = -.27, P < .01) in the entire population. These results indicate that variations in the plasma Mg concentration have a relatively modest but significant effect on insulin-mediated glucose disposal in healthy subjects, with lower plasma Mg concentrations associated with increased insulin resistance.

Blood Glucose↗
PubMed1999

[Effect of folates, vitamin B12 and life style factors on mild hyperhomocysteinemia in a population sample].

BACKGROUND: Mild hyperhomocysteinaemia (MHHcy) is a significant and independent risk factor for vascular diseases, however, its causality has not yet been unequivocally confirmed. The total homocysteine (Hcy) blood level is considered a product of genetic and lifestyle interactions, mainly folates, vitamin B12 and pyridoxine intake. In this paper we estimated the influence of these factors on MHHcy in the population. METHODS AND RESULTS: The population sample included 292 males a 251 women, mean age 53.4 years, selected from the population study PILS II. All subjects were examined by a standard protocol for clinical, anthropometrical and laboratory examination. Hcy levels were examined by ion exchange chromatography, all other factors by commercial kits. Statistical analysis was done in quartiles of distribution by Kruskal-Wallis ANOVA, Wilcoxon's un-paired test and multiple logistic regression (stepwise). Serum total Hcy levels were in significant positive associations with age in both sexes, with BMI in males only. Negative associations of Hcy were found with plasma folates and B12 concentrations in both sexes, with alcohol consumption again only in males. Smoking and physical activity and serum methionine concentration were not associated with Hcy levels. The established associations remained significant when adjusted by multiple logistic regression. About 40% of subjects with MHHcy had low folates and/or B12 levels and a deficiency in both vitamins was found in 17% of subjects. In contrast, MHHcy also was assessed in 14% of subjects with high folates and in 17% with high B12 concentration and in as few as in 3.7% of subjects with high concentrations of both vitamins as well. CONCLUSIONS: Nutritional factors, i.e. folates and B12 intake, seem to be the most important ones responsible for Hcy levels. A predominating influence of genetic factors may be assumed in less than one fifth of subjects with MHHcy.

Alcohol Drinking↗
PubMed1999

[Gender differences in serum homocysteine levels and associated factors].

BACKGROUND: Homocysteine (Hcy) is an important independent risk factor for vascular diseases. Its level is determined by genetic polymorphism of several enzymes in association with nutritional factors. Higher Hcy levels were found in men than in women, however the clinical significance of this phenomenon remains to be elucidated. The aim of this study was to analyze the gender differences in Hcy levels in relation to associated factors and to assess in which range of Hcy these differences are mainly expressed. METHODS AND RESULTS: The series comprised of 257 males and 239 females, mean age 52.9 and 52.3 years, resp., selected from the population study Pils II. All subjects were examined by a standard protocol, to assess clinical, anthropometrical and laboratory variables. Hcy and methionine levels were estimated by ion exchange chromatography, other laboratories using standard kits. The methods were validated by a reference laboratory. Statistical analyses were done by Wilcoxon's unpaired test and multiple linear regression. We found in males significantly higher Hcy levels (13.1 vs. 11.5 mumol/l, p < 0.0001) than in females. This difference persisted only in the range of normal Hcy levels (11.1, 10.2 mumol/l, p < 0.0001), i.e. up to 15 mumol/l (1st-4th quintile of the Hcy distribution) and not in the top quintile, considered as mild hyperhomocysteinaemia. We found in males, with normal Hcy levels, significantly higher serum methionine (23.8 vs. 22.4 mumol/l, p < 0.0001), creatinine (91.5 vs 80.9 mumol/l, p < 0.0001) and a lower methionine/creatinine ratio (0.25 vs. 0.27, p < 0.01). Plasma folates and B12 vitamin in males were also lower than in females, however these differences were only of a borderline statistical significance. On the other hand, in subjects with MHHcy (5th quintile) no gender differences were observed, except in creatinine. CONCLUSIONS: Higher Hcy levels in males cannot be explained by differences in folate and B12 levels only. We considered also other factors, namely higher demethylation of methionine associated with higher creatinine production in males, which may be influenced by sex hormons.

Creatinine↗
PubMed1998

[Analysis of mortality trends in the West Bohemian Region in comparison with the entire Czech Republic 1988-1995].

BACKGROUND: Unfavourable trends in Czech republic (CR) started in the sixties and peaked in the late eighties i.e. in years when a dramatic mortality fall was observed in most western european countries. So, CR belonged among those Eastern European countries in that total and cardiovascular mortality showed increasing and alarming trends. West Bohemia Region (WB) was characterised by the concentration of heavy industry and high environmental pollution. Because of its geographical position on the western frontier, it was generally restricted in capital investment in the past. We wondered whether these phenomenon were reflected in higher mortality rates than in the rest of CR and which changes occurred after the year 1989. METHODS AND RESULTS: We compared the age standardized mortality data from 1988, 91, 93 and 95 in CR and WB for total mortality, cardiovascular mortality, coronary heart disease, strokes, malignancies and respiratory diseases. Data were age-adjusted for "World Population Standards" and rates were given for 100,000 inhabitants. In the whole CR a significant decrease of total, cardiovascular and cancer mortality was observed from 1988 to 1995. In WB these trends were similar, however in comparison to the whole CR the mortality rates remained in each respective period higher for total, cancer (mainly lung cancer) mortality and for non specific respiratory disease. In contrast, the coronary mortality rates in CR and WB were similar, however in WB after a temporary decrease in 1993 a significant increase in 1995 was observed. On the other hand the stroke mortality rates which were until 1993 in WB higher, significantly decreased in 1995 below the rates for CR. The cause of higher mortality rates in WB are far from being clear. To elucidate this observation epidemiologic studies of environmental pollution, life style of the population and socioeconomic factors are necessary, even as a further monitoring of regional mortality rates and trends.

Cause of Death↗
PubMed1998

[Calcium channel blockers in the treatment of hypertension and ischemic coronary disease. Conflicts in their evaluation].

Calcium channel blockers represent a pharmacologically non homogenic group. Verapamil and diltiazem have myocardial component of their effect, which acts against activated sympathicus. Short acting dihydropyridines (nifedipin) appear to be harmful by patients after myocardial infarction which is caused by the reflex sympathetic response to the predominant vasodilation. In the treatment of cardiovascular disease (e.g. hypertension, coronary vascular disease) are short acting dihydropyridines not recommended. Dihydropyridines of the new generation (amlodipin, felodipin, isradipin, lacidipin, nicardipin, nimodipin, nisoldipin, nitrendipin) induce less tachycardia due to their favorable kinetic features. If the slow movement in blood or at the receptor site is not a result of molecule features there is necessary to use retarded preparations of active substance. Nevertheless, commonly used retarded preparations fulfil this requirement only incompletely. The desirable quality is provided by modern form of retardation. (e.g. GITS) only.

Calcium Channel Blockers↗
PubMed1998

[Detection of risk of insulin resistance in the population].

BACKGROUND: To assess the validity of hyperinsulinemia as a marker of insulin resistance (IR) and to find other common risk factors (RF) associated with IR. METHODS AND RESULTS: Sample of 91 healthy volunteers with normal glucose tolerance (NGT) was selected from the adult Pilsen population. Following examinations according to the standard protocol were done: medical history, physical examination, body mass index-BMI (kg/m2), waist to hip ratio (WHR), casual blood pressure (BP), plasma lipids, 7-point oral glucose tolerance test (oGTT), IRI (immunoreactive insulin) curve, insulin suppression test (IST) for the evaluation of IR. Specificity and sensitivity of IRI levels as markers of IR were tested. Association between IR measured by IST and fasting and postload IRI was evaluated by single correlation. Multiple logistic regression (MLR) was applied for the calculation of IR prediction. Fasting and postload hyperinsulinemia (mU/l) have very good specificity (about 90%) for the discovery of IR, but sensitivity was different: fasting IRI > 20 = 19%, IRI in the 2nd h of oGTT > 90 = 30%, IRI sum (fasting IRI + IRI in the 1st and 2nd h of oGTT) > 150 = 51%. Simple correlation between IRI and IR was better in IRI sum (0.56 p < 0.001) than fasting IRI (0.28, p < 0.05). Using MLR HDL-ch, TG and IRI sum were selected as the significant and independent factors for the prediction of IR in the subjects from the population (prediction accuracy about 68%). CONCLUSIONS: Fasting IRI is not too good marker for IR assessment in the NGT subjects from the Pilsen population. IRI sum was the best marker for IR and together with HDL-ch and TG level were selected as the significant predictive factors for IR.

Adult↗
PubMed1998

Pharmacokinetics of orally administered estradiol valerate. Results of a single-dose cross-over bioequivalence study in postmenopausal women.

A randomized, single-dose cross-over study in 32 postmenopausal women was performed to demonstrate bioequivalence of two estradiol valerate containing formulations (first sequence of Klimonorm as test preparation). The serum levels of estradiol, free and conjugated estrone were measured until 48 h after an oral dosage of 4 mg estradiol valerate (CAS 979-32-8). The mean AUC(0-48) of estradiol was calculated as 1006.6 +/- 479.4 h x pg x ml-1 (Test) and 1015.2 +/- 555.2 h x pg x ml-1 (Reference). The corresponding (AUC(0-48) of the active metabolite, free estrone, exceeded that of estradiol at 3578.3 h x pg x ml-1 (Test) and 3485.1 h x pg x ml-1 (Reference). Much higher was the AUC(0-48) for conjugated estrone at 132.4 h x ng x ml-1 (Test) and 133.6 h x ng x ml-1 (Reference). Mean estradiol Cmax values of 39.8 +/- 17.7 pg/ml (Test) and 42.9 +/- 21.0 pg/ml (Reference) were attained 8.2 +/- 4.5 h (Test) and 10.0 +/- 5.9 h (Reference) after the administration of 4 mg estradiol valerate. Maximal free estrone concentrations of 163 pg/ml (Test) and 174.3 pg/ml (Reference) were reached after 7.2 h (Test) and 7.5 h (Reference). Maximal conjugated estrone concentrations of 15.5 ng/ml (Test) and 16.2 ng/ml (Reference) were reached after 2.4 h (Test) and 2.0 h (Reference). The terminal elimination half-life of estradiol was calculated at 16.9 +/- 6.0 h (Test) and 15.0 +/- 4.8 h (Reference), that of free estrone at 16.3 h (Test) and 13.5 h (Reference), that of conjugated estrone at 11.8 h (Test) and 10.6 h (Reference). After logarithmic transformation, the 90% confidence intervals of the AUC(0-48) and Cmax ratios for estradiol and also for the metabolites (free and conjugated estrone) were within the acceptance ranges for bioequivalence. Therefore the test preparation and the reference preparation are bioequivalent.

Administration, Oral↗
PubMed1997

Effect of variations in plasma magnesium concentration on resistance to insulin-mediated glucose disposal in nondiabetic subjects.

Eighteen nondiabetic volunteers were selected for these studies on the basis of their plasma magnesium (Mg) concentrations defined as being either high (> 0.83 mmol/L) or low (< 0.80 mmol/L). Although different in Mg concentration (0.90 +/- 0.02 vs. 0.73 +/- 0.01 mmol/L), the 2 groups were comparable in terms of age, gender distribution, body mass index, and waist to hip girth. Measurements were made of their plasma glucose and insulin concentrations in response to a 75-g oral glucose load and the steady state plasma insulin and glucose (SSPG) concentrations at the end of an 180-min infusion of octreotide, insulin, and glucose. The low Mg group had significantly higher plasma glucose (P < 0.001) and insulin (P < 0.002) concentrations after the oral glucose challenge. Although the steady state plasma insulin concentrations were similar during the infusion study, the SSPG concentration was significantly (P < 0.001) greater in the low Mg group (11.9 +/- 0.9 vs. 6.6 +/- 0.9 mmol/L). Finally, when the 18 patients were analyzed together, there were significant (P < 0.05 to P < 0.01) inverse correlations between Mg concentrations and glucose (r = -0.68) and insulin (r = -0.51) areas and SSPG concentrations (r = -0.60). Thus, a low Mg concentration in nondiabetic subjects was associated with relative insulin resistance, glucose intolerance, and hyperinsulinemia.

Adult↗
PubMed1996

Effect of diprafenone on the pharmacokinetics of digoxin.

This study was conducted to investigate the effect of diprafenone on the steady-state pharmacokinetics of digoxin. Twelve healthy men, all rapid hydroxylators of debrisoquine, received digoxin (0.5 mg per day over 7 days with a loading dose of 2 x 1 mg) or digoxin and diprafenone (3 x 100 mg per day) in three different phases, without a wash-out period (phase 1, digoxin alone; phase 2, digoxin + diprafenone; phase 3, digoxin alone). Blood and urine samples were collected for pharmacokinetic analyses. Diprafenone caused a statistically significant increase in digoxin trough concentrations [1.4 (SD 0.2) vs 1.6 (0.3) ng.ml-1], AUC(zero)-24 values [41 (7) vs 48 (9) ng.h.ml-1 and Css-max[3.9 (0.6) vs 5.5 (0.9) ng.ml-1]. In all volunteers the parameters tended to return to the original values after administration of diprafenone was discontinued [1.4 (0.3) ng.ml-1, 39 (11) ng.h.ml-1, and 3.9 (1.1) ng.ml-1 for trough concentration, AUC(zero)-24 and Cmax respectively]. The mean relative magnitude of the increase in AUC(zero)-24 and trough concentration values corresponded to the mean relative decrease in the renal clearance of digoxin (in both cases approximately 20%). This suggests that the increase in AUC and Css was caused by reduced renal clearance of digoxin.

Adrenergic Agents↗
PubMed1996

Influence of food on the bioavailability and some pharmacokinetic parameters of diprafenone--a novel antiarrhythmic agent.

OBJECTIVE: The present study was done to investigate the effect of food on the bioavailability of diprafenone. METHODS: The most important pharmacokinetic parameters (Cmax, t1/2, AUC) and the relative oral availability of a solid oral preparation of racemic diprafenone were investigated when administered to fasting subjects and 10 min after a standard meal, in an open, randomised, crossover trial. Single oral doses of 100 mg were given on two different occasions, at least 1 week apart. The serum concentrations of diprafenone and its hydroxy-metabolite were determined up to 24 hours after administration by a sensitive, specific HPLC method. Fifteen healthy, male volunteers were enrolled in the trial. Their mean height, weight and age were 183 cm, 80 kg and 22 years, respectively. Fourteen volunteers were found to be rapid hydroxylators and one was a slow hydroxylator of debrisoquine. Only data from the rapid hydroxylators were used in the statistical analysis. RESULTS: Food increased the oral bioavailability of diprafenone by approximately 50%. This effect was similar in rapid and in slow hydroxylators. The only slow hydroxylator in this trial had an AUCzero-last ratio (with food/fasting) of 1.54. These findings suggest that diprafenone should be administered in a constant temporal relationship to food.

Administration, Oral↗
PubMed1995

[The bioequivalence of two oral propafenone preparations].

The bioequivalence of two oral racemic propafenone (CAS 54063-53-5) preparations was tested in an open, randomised, crossover trial with administration of single doses of 300 mg on two different occasions with a washout period of 7 days. 24 healthy, male volunteers, all proved to be rapid hydroxylators of debrisoquine, were enrolled in the trial. The concentrations of R(+)-, S(-)-propafenone and 5-hydroxypropafenone (5-OH-propafenone) were measured up to 12 h after administration by means of a sensitive and specific HPLC method that allowed the simultaneous quantification of all three substances in plasma. The results of 23 volunteers were evaluated pharmacokinetically. Main target parameters were AUC0-infinity and Cmax of both enantiomers of propafenone. Secondary target parameters were AUC0-infinity and Cmax of 5-OH-propafenone as well as tmax for R(+)- and S(-)-propafenone. The 90% confidence intervals for AUC0-infinity for R(+)-, S(-)-, and 5-OH-propafenone were 0.85-1.07, 0.83-1.10 and 0.84-1.05, respectively. The confidence intervals for Cmax were 0.81-1.12, 0.82-1.17 and 0.87-1.09 for R-, S-, and 5-OH-propafenone, respectively. The concentration maxima of both enantiomers were registered on average 15 min earlier after administration of the test preparation. This difference is of no clinical relevance. Both preparations are bioequivalent according to the criteria of the Committee for Proprietary Medicinal Products (CPMP).

Administration, Oral↗
PubMed1995

[Pharmacokinetics and pharmacodynamics of calcium channel blockers].

The author presents a review of the chemically heterogeneous group of calcium antagonists, focused on their pharmacodynamic properties. He includes in the older generation of calcium antagonists drugs like verapamil, dihydropyridines (nifedipine) and dilthiazem (Diacordin, Blocalcin). The newer generation of dihydropyridines comprises substances with a higher vascular selectivity at a concentration of lower order. The latter include felodipine (Plendil), isradipine (Lomir) and nitrendipine (Baypress). The third generation includes drugs like amlodipine (Norvasc) and lacidipine. The slow onset of action of amlodipine is associated with a decline of undesirable side effects, such as flush, tachycardia, headache, oedema of the ankles. An advantage is also the prolonged effect when a single dose per day is administered.

Calcium Channel Blockers↗
PubMed1994

[High-resolution computed tomography (HRCT) of the lung in collagenoses: a prospective study of 73 patients].

To determine pulmonary features of collagenous vascular diseases as assessed by high resolution computed tomography (HRCT) we performed a prospective study of 73 consecutive patients, 44 with rheumatoid arthritis (ra), 11 with progressive systemic sclerosis (pss), 8 with systemic lupus erythematosus (sle), 5 with sjögren's syndrome, 3 with dermato-/polymyositis and 2 with mixed connective-tissue disease. Pathological lung changes were demonstrated in 70% of patients with ra, 91% with pss, 63% with sle and 60% with the rest. HRCT features included: intralobular thickening (48%) with a predominance in posterior lower and middle lung areas, pleural thickening (48%) with a predominance in upper lung areas, prominent interlobular septa (37%), subpleural lines (33%), parenchymal bands (33%) with a predominance in lower and anterior lung areas, honeycombing (33%), ground glass pattern (29%) with a predominance in upper and middle, micronodules (18%) with a predominance in upper lung areas and bronchiectasis (14%). HRCT is an important means for the assessment of lung changes associated with collagenous vascular diseases and a definite diagnosis is possible in most cases.

Adult↗
PubMed1993

[Comparison of the effects and safety of atenolol and nifedipine in the treatment of angina pectoris].

The effects of atenolol (100 mg/day) and nifedipine (60 mg/day) on angina symptoms and exercise tolerance were compared in an open, randomized study. Twelve-week treatment period was compared with two weeks of placebo treatment in 51 patients with chronic stable angina pectoris. Mean frequency of angina attacks decreased significantly from 8.3 to 1.6 attacks per week after atenolol treatment (p < or = 0.05). Both drugs increased exercise tolerance to development of signs of ischemia on electrocardiogram (p < or = 0.05) and increased maximal exercise tolerance as well (p < or = 0.05). Mean ST segment depressions at peak exercise were significantly decreased after treatment with atenolol and nifedipine (p < or = 0.05). Both drugs also increased total exercise capacity in comparison with placebo period, stated as 100%:192% after atenolol and to 191% after nifedipine. No significant changes of heart rate and blood pressure were noted during treatment period. Twelve patients did not finished study, two of them suffered myocardial infarction with death in one of them (atenolol group, other one nifedipine group). Thus, atenolol in one daily dose is as effective as nifedipine in chronic stable angina patients when administered as single therapy.

Adult↗
PubMed1993

[The antihypertensive effect of isradipine and additional pharmacodynamic effects].

The authors demonstrated that isradipine reduces the blood pressure assessed at rest in patients with mild to medium severe hypertension. The antihypertensive action was enhanced by administration of beta-blockers. In a loading test the pressor response to strain was reduced in particular as regards diastolic pressure; from this in may be concluded indirectly that a vasodilatating effect is involved. The authors recorded a rise of plasma renin activity which may be associated with previous vasodilatation. Parameters of lipid metabolism were influenced by isradipine. The indifference of isradipine as regards the effect on functions indicated by biochemical screening was again confirmed in the present investigation. The undesirable effects typical for calcium antagonists were manifested in a very small percentage of the investigated subjects and in a small number of repeated examinations. The reason for discontinuation of treatment in one patient was an effects which does not threaten the patient (flush). Isradipine is an effective antihypertensive drug with very good tolerance.

Adult↗
PubMed1992

[Multicenter study of isradipine in the treatment of hypertension].

MIS is a one-year Multicentre Isradipine Study of the treatment of essential hypertension, in which participated seven centres in Czechoslovakia. The study comprised 144 patients with mild or medium severe hypertension. Isradipine belongs into the group of dihydropyridine derivatives with a high specific and low non-specific affinity to dihydropyridine binding sites of the L-type of calcium channels. After a four-week placebo period isradipine treatment (2.5 mg (1/2 tablet twice a day/was started. This dose increased to 5 mg (1 tablet twice a day) unless normalization of the diastolic pressure was achieved by a smaller dose. Monotherapy with isradipine normalized the diastolic pressure (less than 90 mmHg) in 44% of the hypertonic patients. 56% hypertonics where monotherapy with isradipine did not reduce the diastolic pressure below 90 mmHg were treated by a combination of isradipine and bopindolol. This group of patients had a significantly higher systolic and diastolic pressure, a higher number of erythrocytes and thrombocytes at the onset of the investigation. Addition of bopindolol to isradipine proved very effective. At the end of the one-year study 87% of the patients had a normal diastolic pressure. Isradipine as monotherapy and combined with bopindolol did not influence the metabolic risk factors of IHD and drug tolerance was very good.

Adrenergic beta-Antagonists↗
PubMed1992

MIS (Multicentric Isradipine Study of antihypertensive therapy).

One-year open Multicentric Isradipine Study (MIS) performed in 7 centres in Czechoslovakia included 144 patients with mild and moderate hypertension. Isradipine was given at a dose of 2.5 mg daily. If normalization of diastolic blood pressure (BP) had not been reached, the dosage was increased to 5 mg. Monotherapy with isradipine normalized diastolic BP in 44% of patients. Isradipine (5 mg daily) was combined with bopindolol in patients in whom isradipine alone failed to normalize diastolic BP. These had higher mean systolic and diastolic BP, body weight, erythrocyte and platelet counts at the beginning of the study. The combination of isradipine with bopindolol normalized diastolic BP in 87% of the group at the end of 48 weeks' treatment. Tolerance was excellent in 82% of patients. Treatment was discontinued in 8% patients, undesirable effects being the reason in 2%, ineffective therapy in 2% and poor adherence to therapy in 4%. Isradipine in monotherapy or in combination with bopindolol did not exert an adverse effect on the metabolic risk factors of ischaemic heart disease (cholesterol, glycaemia).

Adrenergic beta-Antagonists↗