[Determination of cystatin C in serum and its use in prediction of glomerular filtration].
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Cystatin C↗
Biomedical subjects
D Stejskal
Publications and source records attributed to D Stejskal.
[Serum leptin, early atherosclerosis and hypolipidemia (a new, previously undescribed effect of pravastatin, a hypolipemic agent)].
Hyperleptinemia is considered to be one of predictors of early atherosklerosis complications. This stimulated us to investigate differences between leptinemia in persons with accelerated atherosclerosis and leptinemia in probands without atherosclerosis complications. The study also verified whether leptinemia and its relationship to other anthropometric and biochemical parameters can differ in hypolipemic-treated probands and hypolipemic-untreated individuals. We examined 89 probands with accelerated atherosclerosis. The controls were 20 persons without any signs of accelerated atherosclerosis. Probands with accelerated atherosclerosis had a slight hyperglycemia and were slightly obese, but they did not meet criteria of metabolic cardiovascular syndrome. No significant differences between both groups under study were found in terms of anthropometric and biochemical parameters (BMI, % body fat, glycemia, insulin, C-peptide, intact proinsulin, total proinsulin cholesterol, HDL, triglycerides, LDL, homeostatic model of insulin secretion and resistance). Leptin concentration was not different as well. Stratification into males and females showed that women had a significantly higher leptinemia and fat tissue mass. Other biochemical parameters were similar in both groups. We suppose that in individuals without signs of metabolic syndrome, leptinemia does not belong among predictors of accelerated atherosclerosis. The accelerated atherosclerosis persons were then divided into subgroups according to medication (28 probands--pravastatin Lipostat 20, 15 probands--phenofibrate Lipanthyl 200M, 9 probands--simvastatin Zocor 20, 47 probands--no hypolipemic medication). No significant differences between the groups were found in terms of the analysed anthropometric and biochemical parameters, except leptinemia. The pravastatin-medicated probands had a significantly lower leptinemia (significant at 99% significance level) which was evidently sex-related than other patients. The pravastatin-administered persons showed no correlation between leptinemia and body fat mass (in contrast to other groups where such a correlation was highly statistically significant). These findings can be explained by a still unclear effect of pravastatin on insulin metabolism and on other factors involved in leptin synthesis and elimination. Thus, a new therapeutic effect of pravastatin can be supposed. This may account for a highly favourable effect of pravastatin on reduced manifestations of atherosclerosis complications event at a low LDL cholesterol decrease (particularly in persons with metabolic cardiovascular syndrome).
Adipose Tissue↗
[Leptinemia in persons with acute myocardial infarct].
The purpose of the study was to verify whether the currently reported relationship between leptinemia and adipose tissue mass can be applied to cases of acute coronary attack. An increased number of cytokines has been reported in severe acute myocardial infarctions so that correlation between cytokines and leptin was investigated. Correlation between standard coronary markers and leptinemia was also studied. We examined 48 probands, patients of the Coronary Unit, Hospital, Sternberk, who were hospitalized for acute myocardial infarction (AMI--16 probands) or for unstable angina pectoris (UAP--22 probands). The persons with AMI had leptinemia and a higher concentration of interleukine-6 (Il-6) and of cardial troponine-I (cTn-I) than individuals without coronary accident (UAP). Early after the acute coronary lesion, leptinemia in persons with AMI displayed a statistically significant positive correlation with concentration of interleukine-6 and subsequently of markers of coronary lesion severity (cTnI). No correlation between leptinemia and body weight was found in those probands. This study proved that leptinemia in the AMI individuals is influenced directly by concentration of cytokines which leads to leptin superproduction by fat cells and leptin resistance.
Adipose Tissue↗
[Serum leptin in women during the third trimester of pregnancy].
Leptin is a small protein produced mainly by adipocytes. Recently, its relationship to obesity has been studied extensively. It was proved that obese individuals have either relative or absolute leptin deficiency. Several years ago, leptin was found to be produced also by the placenta. This stimulated us to study relationship between leptinemia and placental hormones in 85 women in the second gravidity trimester. Within the prenatal screening, these pregnant women were subjected to analysis of AFP, hCG, SP-1 glycoprotein and leptin and the results obtained were processed statistically. The control group consisted of 20 nonpregnant women with tetany. Women in the second gravidity trimester were found to have a significantly higher leptinemia than nongravid women (even with respect to body weight). This may be due to a larger amount of adipose tissue during gravidity and also leptin-resistance. Moreover, we recorded a negative correlation between leptinemia related to body weight and concentration of SP-1 glycoprotein. This finding supports the presumption that mother's leptinemia correlated negatively in the second gravidity trimester with quality and quantity of the placental syncytiotrophoblast. Our findings can be explained as follows: the biological effect of leptin is metabolically unfavourable for the growth of the foetus and the placenta. An increased leptinemia with advancing gravidity can be caused by a larger fatty mass and an increased activity of adipocytes when leptin presence increases in system circulation but the organism begins to be leptin-resistant and an "unfavourable" metabolic effect fort the gravid woman and the foetus is not distinct. These findings thus support the hypothesis postulating the nonsignificance of leptin production in human placenta and on the contrary the necessity of leptin-resistance for foetus development from the metabolic point of view. Thus, a decreased leptinemia immediately before and after the delivery could be caused by the still unclear regulators of leptin sensitivity. This is again a metabolically highly favourable state (reduced appetite, decreased body weight, increased energy output and others).
Adipose Tissue↗
[Benefit of direct determination of LDL-cholesterol (comparison with LDL measurement using calculated estimates].
Treatment of dyslipidemia and its frequently associated complications (manifest atherosclerosis) is very pretentious from the economic aspect. Diagnostic and therapeutic criteria are based mainly on biochemical analyses. Although demands on laboratories are relatively strict (respecting defined laboratory errors, analytical and preanalytical conditions), when defined diagnostic criteria are used, the results of biochemical analyses are not yet satisfactory. A typical example is the stratification of risk patients according to the LDL concentration which in our country is very often preferred, although the LDL concentration is based only on calculation (contrary to investigations from which the majority of recommendations was derived where the LDL concentration was assessed directly). We know from our own experience that a large percentage of results of estimated and assessed LDL differs significantly. Therefore we wanted to know whether the assessed LDL concentration correlates with its estimate according to Friedewald s formula and which analytes have the greatest impact on the LDL concentration. Our objective was also to assess th percentage of incorrectly listed patients (according to the LDL stratification scale). In 1997-1998 we examined a group of 4578 probands, patients of the consultant out-patient departments of the Sternberk hospital. Their mean age was 56 years. On average subjects with as slightly atherogenic phenotype were involved (classification A according to EAS). The values of lipid parameters did not differ significantly in the two sexes. The cholesterol, LDL and triacylglycerol concentrations increased with advancing age. The LDL values obtained by assessment and calculation correlated closely. The LDL value was influenced most by ApoB and total cholesterol. Triacylglycerols correlated with LDL assessment only up to a concentration of .3 mmol/l. HDL, ApoA-1 and higher triacylglycerol concentrations (1.3 mmol/l) did not correlate with the LDL value. The authors provided evidence that in subjects where it was possible to calculate LDL lege artis (2458 probands) were listed according to LDL calculation into a wrong group (stratification according to NCEP) whereby up to an LDL concentration .11 mmol/l this parameter cannot be predicted at all by calculation (error up to 85%). A satisfactory estimate is assumed only at LDL concentrations 5.2 mmol/l. Because the estimated LDL values are in the majority of patients lower than the calculated values, it may be assumed that during stratification of LDL obtained by calculation the patients are treated too aggressively. Assuming pharmacological treatment of all mentioned patients, it may be estimated that by using analyses of direct LDL for stratification of probands the costs of hypolipidaemic treatment will by reduced by about 1/4-1/3 (in the catchment area of the Sternberk hospital this would save more than 10 million crowns). The costs of LDL analyses per year are about 180,000 crowns (in the Sternberk hospital--which amounts to cca 1.5% of the money saved on pharmacotherapy).
Adolescent↗
[Clinico-teratologic counseling and the Teratology Information Service].
Medical records of 1179 pregnant women counselled at the Department of Medical Genetics Klimentska during the period 1990-1995 because of exposure to medicaments during the preconception period and in the first trimester were analyzed. Women exposed to antimicrobial agents prevailed (48 per cent). Most frequent was treatment with Doxycycline, Co-trimoxazole and Metronidazole. 23 per cent of women were exposed to sex hormones, most frequently to oral contraceptives and norethisterone. The average gestational age at exposure to antimicrobial agents was 21.5 days and 30 days at exposure to sex hormones. Specific features of clinical-teratological counselling and the role of the Czech Teratologic Information Service are described.
Counseling↗
[Determination of cardiac troponin-I in prediction of thrombolysis].
Acute myocardial infarction (AMI) is a disease with high morbidity and mortality. Diagnosis of AMI using common methods (classical biochemistry, ECG) fails even in the fifth part of patients so that other noninvasive diagnostic methods are preferred. Recently, the biochemical analysis has been restored in the case of AMI diagnostics and also in prediction of coronary reperfusion after administration of a fibrinolytic agent. A suitable markers of AMI diagnostics is a combination of myoglobin and cardial troponin-I which is reported as a marker with high specificity and sensitivity. To determine coronary reperfusion, the examination of cardial troponin-T and CK-MB mass is recommended. In the literature, there exist isolated papers dealing with dynamics of cTn-I suitable for prediction of coronary revascularization. However, these papers do not report any adequate algorithm and subsequently mathematical differences between successful thrombolysis and failing thrombolysis. Therefore the aim of our study was to describe dynamics of cTn-I changes in AMI patients treated by thrombolysis. The study comprised of 8 AMI patients with delay from the occurrence of pains to fibrinolysis application under 4 hours (delay 4 hrs). These probands were examined for concentration of cTn-I and CK-MB mass in 3-hour intervals in the first 48 hours after admission to the clinic and further in 6-hour intervals from the hour 48 to the hour 90 after admission. All probands had a successful reperfusion (estimated using CK-MB peak, in 4 patients reperfusion was verified by subsequent coronarography). However, a simple mathematical prediction of coronary reperfusion after acute myocardial infarction by means of cTn-I dynamics determination is not possible due to relatively low cTn-I differences in individual analyses (CK-MB mass analysis shows more significant differences). Thus, in order to determine coronary revascularization, we recommend to use common analyses of dynamics of cTn-T or CK-MB mass.
Biomarkers↗
[Leptin, insulin and proinsulin--their relationship].
Leptin is protein produced by mature adipocytes into the system circulation and gives information to hypothalamic centers about fat amount in the organism. Leptin is supposed to play a causal role in energy output of the organism and influences the appetite (antiobese effect). Obese individuals were proved to have frequently hyperleptinemia. This disease is caused by a postreceptor disorder (however, several obese families had also normoleptinemia or even hypoleptinemia which is caused by polymorphism of Ob-gene). It was also found that leptin administration in animals leads to reduced appetite and decreased body weight. Interpretation of leptinemia in human is very complicated because leptinemia is influenced by many independent regulations (hormones, stress, food intake, motor activity atc.). Obesity is often associated with hyperinsulinemia and insulin resistance (a frequent cause of human mortality) so that correlations between insulin and leptin are intensively studied. Experimental models and animal studies revealed the existence of adipoinsular axis and it was found that insulin and leptin are contrahormones. In human studies, the majority of authors did not find correlation between leptinemia and markers of insulin secretion. Similar conclusions were drawn out in our previous paper [118]. This may be due to complex regulations of leptinemia in the organism and the use of biochemical markers with limited validity (insulin, C-peptide in fasting state and after stimulation). Therefore we decided to study correlation between leptinemia and intact proinsulin in the serum which is now considered to be the most valid marker of insulin secretion and provides information about an average "daily" insulinemia. This study was stimulated by the fact that increased leptinemia is found also in persons with prolonged hyperinsulinemia (a short-term hyperinsulinemia does not affect leptin concentration so that no available marker of insulin secretion is valid). We examined the group of 31 probands, patients of the Metabolic and Diabetologic Center at the hospital in Sternberk. They were diabetic patients of type 2 who were treated by peroral antidiabetics and insulin and who met criteria of good compensation. However, no correlation between leptinemia and proinsulinemia was found. We suppose that this failure was due to complicated fine regulations affecting leptinemia and also to the fact that intact proinsulin is not an "ideal" marker of a long-term hyperinsulinemia (correlation between insulin and leptin at euglycemic clamp indicates that there exist correlation between these parameters in human).
Adipose Tissue↗
[Biochemical diagnosis of acute coronary disorder].
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Biomarkers↗
The invasive prenatal diagnosis in perinatal centre.
Three main methods of prenatal diagnosis (Amniocentesis AMC, Chorionic villi sampling CVS and Cordocentesis FBS) have been used in Perinatal Centre of Central Bohemia. The chromosomal abnormalities in a group of 3,098 patients have been detected in 1.4% of fetuses. The inherited disorders were diagnosed using DNA analysis and biochemical examination of amniotic fluid. X-linked diseases in a group of 68 patients in 30.8% of fetuses have been diagnosed and inborn error of metabolism in a group of 29 indicated patients in 17.2% of fetuses were diagnosed. The incidence of fetal losses before 28th week of gestation was 0.4%.
Chromosome Aberrations↗
[Kinetic analysis in the evaluation of glucose tolerance disorders. Evaluation and use of a new method in the diagnosis of glucose tolerance in clinical practice].
A kinetic model of oGTT has been used. This model is characterized by 7 glycaemia collections (0, 30, 45, 60, 120, 180 min). In some cases this is supplemented by determination of C-peptide and insulin values (0, 60, 120 min). This method is very simple and highly useful in clinical practice because it gives information about physiological stimulation by enterohormones, the first glucose passage through liver and next glucose utilization. The first part of the study deals with random error of the kinetic model of oGTT found by repeated calculations (> 10,000 repeatings) of identical initial glycaemias in individual groups (DM, PGT, N). Random error of glucose clearance (the most suitable parameter) ranged within 0.2 -2.1% in individual deviations. Then the identical calculations were made but loaded with glycaemia and with certain error in individual collection intervals (glycaemia 0.1, 0.2, 0.5 mmol/l; collection with 30, 60, 300 s). Random error of the method increased significantly with dispersion variance of glycaemias (maximum 17% with glucose clearance at glycaemia dispersion variance of 0.5 mmol/l); changed time intervals less affected random error quantity. As acceptable and frequent deviation in practice was determined glycaemia dispersion variance of 0.2 mmol/l (corresponding to a total analytical error of glycaemia measurement) and dispersion variance of time intervals of 60 s. At these values, random error of the method increased maximally to 10.3%. Glucose has also a biological variability (not published yet for individual time intervals), the value of random error may be higher but will not achieve half of values of random error obtained at the classical oGTT. The second part of the study deals with comparison of both the tests (classical oGTT, kinetic curve of oGTT) in 126 probands examined at metabolic and diabetologic out-patient department of the Hospital in Sternberk. It can be concluded that using a classical oGTT, 60% of patients were classified into incorrect groups as defined by dynamic results obtained by analysis of the kinetic model. Interesting enough is the fact that almost half of persons who cannot be classified by the classical oGTT had impaired glucose tolerance. Out of them, 15.6% had diabetes mellitus; almost 20% of normal patients also had impaired glucose tolerance. Over 1/5 of persons with impaired tolerance for glucose according to the classical oGTT was found by the kinetic model to have diabetes mellitus. On the contrary, 1/10 of diabetic patients diagnosed by oGTT had normal glucose clearance, over 1/2 of patients had only impaired glucose tolerance. Then in 126 persons random error of the method was again calculated (> 2,000 repeated calculations for each proband) amounting 6.6%.
Glucose Intolerance↗
[Personal experience in the diagnosis and monitoring of therapy in metabolic disorders with risk of crystallization in patients with recurrent urolithiasis].
A ten-year experience with diagnosis and therapy of metabolic abnormalities and crystallization risks in patients with recurrent urolithiasis is presented. Since 1985, more than 900 persons with recurrent urolithiasis have been examined at the Metabolic Centre of the Hospital in Sternberk. The patients were examined routinely at ambulance or during hospitalization; the examination consisted of repeated urine and blood collections after the diet with various content of calcium and salt. All initial data (case history, physical finding, biochemistry, radiodiagnostics) were processed by a semi-expert computing program SOFT which was also used for monitoring of the therapy. Then the patients were divided into individual risk groups (Pak). Of all probands, the group of 130 patients (satisfying the strict criteria of the study) was selected and the data obtained was processed statistically. The group of 130 patients with recurrent urolithiasis (all of them were drug-treated) was compared to the group of 50 individuals with urolithiasis treated by diet and regimen measures. The patients given drugs showed a significantly increased crystallization inhibitors concentration in urine and reduced crystallization promotors, or relative saturation of some lithiatic substances. The paper analyzes the effect of the mostly administered drugs on crystallization risks and some less known "metabolic" indications of application of some drugs are recommended. It is concluded that the dietary, drinking and regime measures are basic for a good therapy of patients with urolithiasis, but patients with recurrent urolithiasis should be applied a selective metaphylaxis of drugs after routine metabolic examination. This finding is supported by a low number of recurrent urolithiasis.
Adult↗
[Leptin in persons with simple obesity].
Obesity is a disease with distinct genetic determination and its phenotype is defined by the still unknown number of genes whose expression can be influenced by environmental factors. Several years ago, "obesity gene" was isolated in animals. This gene, coding protein which consists of 165 amino acids, is called leptin. Leptin is supposed to be a key substance controlling homeostasis of body weight and energy balance; it is produced by adipocytes and its value correlates highly significantly with anthropometric parameters that characterize physical constitution and amount of subcutaneous fatty tissue. The obese individuals often display hyperleptinemia which is frequently caused by a postreceptor disorder; sporadically, a different leptin structure or hypoleptinemia (caused by genetic anomaly) are reported. It is supposed that either absolute or relative leptin deficiency in obese persons are associated with causal obesity (e.g. appetite stimulation). Leptinemia values correlate with percentage of subcutaneous fatty tissue, insulinemia and sometimes with glycemia. In our study we examined 200 probands, patients of the Metabolic and Diabetologic Out-Patient Department, Hospital in Sternberk. A very close correlation between the amount of subcutaneous fatty tissue (measured by a caliper in 10 skinfolds) and the leptine serum concentration was found. The values of leptinemia in men of normal constitution ranged within 1-11 ng/ml, non-obese women had 3-4 times higher values. Leptinemia in some obese individuals reached up to 70 ng/ml. However, the currently calculated and reported parameters of physical constitution (BMI, WHR, Grant index) did not correlate significantly with leptinemia. Similarly, biochemical parameters considered as general markers of insulin resistance (often associated with obesity) did not correlate significantly with leptinemia. This finding indicates that some calculated parameters, quantifying and gualifying physical constitution, may be ambiguous and leptinemia was found to give more detailed information about the amount of subcutaneous fatty tissue than WHR or BMI. An accidental finding was an important positive correlation between myoglobin concentration and creatinemia. At monitoring the effect of hypolipidemic agents we use the myoglobin examination and therefore we consider this correlation to be very important and every physician performing this analysis should be informed about it. The present study thus confirmed that a more accurate quantification of subcutaneous fatty tissue is required. On the other hand, we believe that examination of leptinemia can contribute significantly to stratification of patients into risk groups (with respect to clinical, economic and time differentiation) and subsequently to the treatment of these patients. In future, criteria for quantification of leptinemia and leptine resistance should be defined precisely.
Adipose Tissue↗
[Screening for Down's syndrome: results at the Klimentská Polyclinic Screening Center 1992-1994].
Between January 1992 and March 1994 in Klimentska Screening Centre 635 second trimester amniocenteses were performed because of the risk of a chromosomal aberration. 416 (66 per cent) procedures were recommended because of the mother's age over 35 years and 219 ones (34 per cent) because of a positive screening test. Maternal serum alpha-fetoprotein and human chorionic gonadotrophin were used as screening markers in most cases. Five trisomy 21 cases in the advanced age group were detected. Serum markers were assessed in three older mothers with an affected foetus after amniocentesis. All were ex post screen positive. Three trisomy 21 foetuses of mothers younger than 35 years were detected in the screen positive group. Recent advances in screening for Down's syndrome and other congenital defects are discussed.
Adult↗
[Is chorionic biopsy a dangerous and outdated method?].
The authors evaluated the risk of chorion biopsy used within the framework of prenatal diagnosis of the foetus. The incidence of abortions following transabdominal CVS (0.6%) did not differ from abortions after amniocentesis in the second trimester (0.5%). In a group of 1002 diagnostic biopsies of the chorion the authors did not record in the born infants reduction deformities of the extremities. Chorion biopsies were performed in 98% between the 10th and 12th week of gestation. The incidence of mosaicism--1.59%--was not significantly higher than reported in the literature. The authors recommend: to increase the size of the sample of chorion tissue by the use of a manual aspirator, the use of a 30 ml plastic syringe or the double needle method. They consider CVS a suitable method which serves the diagnosis of IUGR and the prenatal diagnosis of the foetus before the 20th week of gestation when cordocentesis involves risk.
Abortion, Spontaneous↗
[Congenital defects and other pathologic states associated with folic acid metabolism disorders (review)].
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Female↗
[Screening for Down's syndrome in the 2d trimester of pregnancy: initial results].
A total of 332 pregnant women with risk of foetal aneuploidy underwent amniocentesis between January 1991 and August 1992: 247 women (74 per cent) for advanced age over 35 years and 85 younger ones (26 per cent) because of significant risk of Down's syndrome as a result of multimarker screening. Maternal serum alpha-fetoprotein, intact human choriogonadotropin and age were used as variables for combined individual risk evaluation according to Wald et al. The Demo version of ALPHA computer programme was used for risk computations. Two prenatally detected cases of Down's syndrome from a total of 5 were from pregnancies of younger mothers aged 18 and 23 years. Various screening protocols and strategies combining age and biochemical variables are discussed.
Adult↗
[Use of fetoplacental antigens in prenatal diagnosis].
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Chorionic Gonadotropin↗