More on: thrombomodulin gene polymorphisms or haplotypes as potential risk factors for venous thromboembolism: a population-based case-control study.
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Adolescent↗
Biomedical subjects
R Pullmann
Publications and source records attributed to R Pullmann.
The significance of clinical markers in the prediction of hemodynamic and cardiac complications of capnoperitoneum in patients at risk.
OBJECTIVES: The aim of this prospective study was to find out the predictive value of concomitant diseases of cardiovascular system (CVS), lungs and kidneys as well as metabolic diseases to be able to anticipate the potential origin of hemodynamic and cardiopulmonary complications as a result of insufflated CO2 peritoneum. METHODS: The study investigated eleven patients at the anaesthetic risk of ASA III-IV and cardiac risk of NYHA II-III in whom elective laparoscopic surgical intervention had been indicated. RESULTS: We have found out that the significance of the increase in biologic ANP markers, catecholamines and PRA was not sufficient to signal the deepening of cardiac dysfunction, latent cardiac failure or hemodynamic disorder (p > 0.01). The courses of regression lines have shown the dependence on the increased IAP (intra-abdominal pressure) of capnoperitoneum in PRA and adrenaline. The reactions of biologic markers correlated with reactions of clinical hemodynamic markers of BP and HR. We have proved that the increased level of IAP causes a significant increase in CVP (p < 0.01) being one of the factors determining the preload of right ventricle (RV) and in coincidence with intact transpulmonary circulation also the optimal function of left ventricle (LV). CONCLUSION: Our investigation of peroperative clinical and biologic markers of hemodynamics and neuroendocrine response to operative stress and development of CO2 peritoneum has proved that the course of laparoscopic operations in patients in the risk group of ASA III-IV and NYHA III does not necessarily have to be deteriorated by complications. It can be assumed that increased values of biologic markers regulate the neurohumoral response in the physiologic range and do not predict a severe CVS dysfunction within its course. (Tab. 2, Fig. 3, Ref. 22.)
Abdomen↗
Angiotensin-converting enzyme insertion/deletion polymorphism and vascular impairment in SLE.
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Genetic Markers↗
[Factor V Leiden and the Slovak population].
The resistance to activated protein C (APC-resistance) based on the presence of factor V Leiden (F V Leiden) is the most frequent thrombophilic condition in the white race population. It contributes to the origin of thrombosis especially in the venous part of blood vessels. Significant geographic differences have been detected within Europe. The aim of this retrospective study was to determine the frequency in the occurrence of F V Leiden: 1. in healthy (asymptomatic) Slovak population, 2. in their consanguineously unrelated members with thrombosis and 3. in patients with myocardial infarction (IM) without or with other known risk factors of this disease (nicotinism, obesity, hypertension, dyslipoproteinemia, diabetes mellitus), respectively. The detection of FV Leiden was made by molecular biology methods. The occurrence in a group of 152 healthy individuals was four % (6 persons) and this frequency corresponds to the geographic localization of the Slovak Republic in Europe. In a group of 349 patients with thrombosis in anamnesis, FV Leiden was detected in 103 persons (29.5%). The occurrence was higher than the usually reported incidence in these patients (20%). Likewise, in a group of 35 patients with IM without risk factors in anamnesis, the occurrence of FV Leiden (8.6%) was significantly higher in comparison with healthy population and the incidence further increased significantly in a group of 41 patients with IM and the presence of at least one risk factor (14.6%). The authors therefore suppose an active role of the Leiden mutation of FV gene in the pathogenesis of this disease.
Activated Protein C Resistance↗
A worldwide analysis of AG molecular diversity inferred from serology.
Ten population samples from different geographic origins were tested serologically for the AG polymorphism of human beta-lipoproteins. Their haplotype frequencies were used with previously published data to perform a wide analysis of AG genetic differentiations throughout the world. Coancestry coefficients were computed from weighted F(ST)s among populations by using a matrix of molecular distances among AG haplotypes, which is here determined on the basis of DNA studies. Coancestry coefficients derived from unweighted F(ST)s and more classical Prevosti distances were computed on the same data and used for a comparison. In all cases a highly significant correlation was found between genetics and geography on a worldwide scale, while the significance of the correlation with linguistics differed. A test of significance of the pairwise F(ST)s among populations also gave different results depending on whether the molecular distance matrix among AG haplotypes was included. Globally, this study shows that in spite of being highly significantly correlated to each other, different genetic distance measures can lead to different interpretations of the same data set. Moreover, the elucidation of the molecular models related to the presently known serological polymorphisms may represent an additional tool for analyzing such polymorphisms in human population genetics studies.
Amino Acid Substitution↗
Assessment of insertion/deletion polymorphism of angiotensin-converting enzyme gene and its clinical importance.
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Alleles↗
[Endothelial dysfunction and lipid profiles: analysis of the EDO Study].
On the basis of experimental as well as clinical observations, endothelial dysfunction is (defined as impaired or absent endothelium-dependent relaxation) considered to be an important factor in the atherogenesis. Serum lipids abnormalities have been accepted as an epidemiological risk factor of atherosclerosis. In vitro, experimental as well as epidemiological studies revealed the fact, that lipoprotein oxidation plays an important role in atherogenesis. Recently invented non-invasive methods to test and measure the endothelial function in vivo opened the opportunity to study the influence of different serum lipids on the endothelial function directly. Therefore, we decided to employ this non-invasive method for studying the endothelial function and observe the influence of various levels of plasma lipids and lipoprotein oxidation on the endothelial function of arteries in middle-aged men, since they are the most endangered part of population. In our study we used a method of measuring the diameter of a. radialis by high-resolution ultrasound (Sonoline 450, Siemens, Japan) and further mathematical and statistical analysis of functional as well as relative vasodilation reserve followed these measurements. Blood samples were taken within 24 hours of ultrasonography to study serum lipids (total cholesterol, HDL, triglycerides) and parameters of oxidation/antioxidation (superoxid dismutase--SOD, malondialdehyde--MDA). Sixty men, 25-45 years old, from an area of basically the same level of pollution were examined. We found a negative correlation between FVDR and TCH (p = 0.01), FVDR and Tg (p = 0.002) and FVDR a TCH/HDL (p = 0.015). Positive correlation exists (p < 0.001) between TCH, Tg levels and TCH/HDL ratio and MDA level in all cases. Analysing further data from the EDO Study, we can conclude, that increased plasma lipids are more likely to be oxidized, which, in turn, is the probable reason of endothelium-dependent vasodilation impairment.
Adult↗
[Is PLA1/A2 gene polymorphism of platelet membrane glycoprotein IIIa a risk factor for myocardial infarct?].
BACKGROUND: The PlA1/A2 polymorphism of the human platelet membrane glycoprotein IIIa gene cause T-->C transition in the exon ii (position 1565) resulting in the leucine-->proline substitution in amino-acid sequence. This polymorphism was shown to be associated with increased risk of myocardial infarction (MI). AIM: To test genetic parameters of the PlA1/A2 polymorphism in our population and to assess the relation between mutant PlA2 allele and MI. METHODS: DNA was isolated from peripheral blood, collected from 40 patients with MI and with present risk factors (hypertension, hypercholesterolaemia, diabetes, obesity, smoking...), 33 patients with MI without risk factors, 34 controls with equivalent average age to both groups of the MI-patients, 58 control probands without MI in their family history and 33 healthy controls randomly recruited. After PCR amplification the resulting 267 bp fragment was digested with the restriction endonuclease NciI and subfragments were separated electrophoretically in 12% polyacrylamide gel. RESULTS: The frequency of the PlA2 allele was 0.121 in patients with MI without risk factors, 0.205 in patients with present risk factors, 0.162 in controls of the equivalent average age to the MI-patients, 0.172 in controls without MI in their family history and 0.20 in healthy controls randomly recruited. Genotype frequencies were in all groups in genetic equilibrium. Although the groups differed significantly (p < 0.01) in serum concentrations of total cholesterol, HDL-cholesterol, LDL-cholesterol, apolipoprotein A-1, apolipoprotein B and malondialdehyde, no significant differences in the serum concentrations of these metabolites between A1/A1, A1/A2 and A2/A2 genotypes were observed. CONCLUSIONS: PLA1/A2 polymorphism is associated with MI, however not as a dominant risk factor, but as a part of environmentally influencable multigene system. There is no relation between genotypes of the PLA1/A2 polymorphism and the lipoproteins plasma concentrations. (Tab. 4, Ref. 17.)
Adult↗
[Analysis of phenotype resistance to activated protein C (APC resistance)].
The laboratory diagnosis of resistance to activated C protein (APC-resistance) involves examination of the phenotype and genotype of this thrombophilia. For examination of the phenotype coagulation and chromogenic tests are used. Their essence is examination in the presence and absence of exogenous APC. While the result of the original coagulation examination of APC-resistance which uses the APTT principle is influenced by a number of factors, the sensitivity and specificity of the modification of this examination (dilution of the examined plasma sample by FV deficient plasma before making the test) in relation to detection of FV Leiden is almost 100% and eliminates the majority of limitations of the original examination. The chromogenic assessment of APC-resistance has similar advantages, however, it cannot differentiate between the heterozygous and homozygous form of FV Leiden. During examination of the genotype of subjects with APC-resistance the mutation of FV Leiden is detected in as many as 90%. The group of subjects with the phenotype of APC-resistance comprises in particular subjects with acquired APC-resistance caused by conditions which lead to a disbalance between procoagulation and anticoagulation proteins of haemostasis which influence the reactions of the applied laboratory examinations. The acquired phenotype of APC-resistance can be also associated with an increased risk of thrombosis and the clinical manifestations of this thrombophilia resemble the classical, FV Leiden conditioned APC resistance. Rarely also congenital causes of the phenotype of APC-resistance are encountered caused by another mutation than the Leiden mutation of gene FV. The concurrent examination of the patient's plasma with the original and modified coagulation test makes it possible to assess the inborn cause of APC-resistance (positive finding also in modified examination). The presence of FV Leiden is then confirmed by examination of the genotype by the polymerase chain reaction.
Activated Protein C Resistance↗
[Ethical problems in molecular genetics and their reflection in clinical medicine].
There are at least two groups of issues connected with an impact of a realization of the "Human Genome Project": a) philosophical; b) ethical, which can be divided into four groups: 1) the influence of DNA technologies on everyday applications of bioethical principles; 2) ethical aspects of genetic diversity; 3) ethical aspects of genetic screening; 4) somatic and germ-cell gene therapy; Unlike essential philosophical issues practical realization of issues in question can be largely expressed as only revitalization of old ones and concerns: the principle of justice-equal access and priorities; protection of reproductive choices; disclosure to patients and to relatives at genetic risk (disclosure and exclusion tests); prenatal diagnosis for "mild to moderate" diseases with and without genetic indication-commercialization; insurance policy; non-directive and directive genetic counseling. Maybe there are regional and other differences, but in practice, the main ethical issues are likely to involve screening for genetic risk of common diseases of adult life e.g. hypertension, diabetes, gout, dyslipoproteinemia, genes for premature atherosclerosis, etc. because of the possible direct impact on a patient, an implication for life-insurance, employers and commercial exploitation.
Ethics, Medical↗
Financial equivalent, industry sponsored research and conflict of interest.
Conflicts of interest for the clinician(physician)-researcher are not limited only to direct and clear financial support by manufacturers of the pharmaceutical and medical device industry, but rather include delicate indirect monetary and research support. Today professionals face an inevitable choice between two opposing moral orders, one based in the primacy of ethical obligations to the sick, the other in the primacy of self-interest and the marketplace. Some medical ethicists urge, reshape ethical codes to conform to the ethos of the marketplace, which legitimates self-interest over beneficence and makes vices out of most of traditional virtues. Second opinion represents the ethicists who recommend a firm stand in belief that being a physician imposes certain specific obligations. Medicine is at heart a moral enterprise and those who practice it are de facto members of a moral community. The market introduces an alien-till this time unknown-set of economic values into an institution (medicine) whose inherent ends are altruistic, but in countries under health care reform it brings a complex of special ethical issues in connection with deficient legislation and not firm ethical rules adopted. (Ref. 17.)
Biomedical Research↗
[Relation between levels of essential fatty acids in maternal milk, in maternal blood and in the blood of neonates 1 and 5 days after birth].
BACKGROUND: Linolenic, linoleic, and arachidonic acids as well as other polyunsaturated fatty acids are necessary for health as the precursors of eicosanoids and for the structure of developing membranes. OBJECTIVES: The aim of the present study was the determination of the level of 11 individual free fatty acids (FFA) in the milk and in the blood of mothers and newborns during the perinatal period. METHODS: In 21 women the FFA was determined in their colostrum as well as in the venous blood at the delivery in the hospital, and then again 5 days later at leaving the hospital. Simultaneously, the blood of newborns was collected as umbilical samples at birth and as venous blood on the 5th day. The study was performed on health term infants and mothers with normal gestational age. RESULTS: The results show a marked increase in total milk FFA as well as in most, but not all, individual FFAs during the followed period of the first 5 days. The values in the milk were always remarkably higher (the increase more than 2 orders) than in the blood. We have found no significant statistical correlation between values in the blood and those in the milk. The concentrations of all very important omega-3 FFAs (which are present in fish oil and in foods of marine fish origin) were always lower in all blood and milk samples in comparison with the levels of omega-6 FFAs (which are prevailing in lipids of our usual nutrition as are margarines and most of commercial oils). CONCLUSIONS: Our findings seem to be very important for preventive medicine and need to study further the relationship of low intake of O3FA to increased incidence of various allergies and other pathological syndromes in children. The very large range of a variance in the values of FFAs in the milk suggests the need of more profound study of the role of the food composition probably during the whole period of pregnancy, mainly as to the type of lipid composition. (Tab. 1, Fig. 6, Ref. 24.)
Fatty Acids, Nonesterified↗
[Metaphylaxis and treatment of cystine lithiasis--personal experience].
The authors presented their own experience with treatment of cystine lithiasis in 7 patients, which has been performed during the course the past of ten years. Identification of cystine was performed by concrement submitted examination, using a polarizating microscope, and x-ray difractometric structural analysis. After stone extraction the patients were treated by a high fluid intake (diuresis over 2.5 l), alcalizating treatment involving citrates (Alkalit Spofa), and Penicilamin (Spofa), or Thiola (Santen) which are currently proved to be the most optimal approach. Recurrence of stones requiring percutaneous treatment, was observed in one of the patients during five years metaphylaxy. Another patient of the same group had three times stated cystine stone recurrence which passed spontaneously.
Adult↗
Development of brown adipose tissue in the rat and thyroxine administration influence.
The role of the thyroid hormone in the activity of brown adipose tissue (BAT) is in most papers underestimated and it is the noradrenaline which is considered as the main regulator. The aim of the presented experiments was the study of the effect of 2 or 3 administrations of thyroxine (T4) applied to young rats of different age on the weight of BAT. T4 was injected in relatively large doses, i.e. 1 microgram/gram BW/day dissolved in 0.005 mmol NaOH intraperitoneally. Changes in T4 injected animals were compared with their litter-mate control, which were injected with solvents. In control animals the relative weight in mg/100 g BW was significantly higher during the entire first postnatal month in comparison with adult animals. Three administrations of T4 caused significant increase in relative as well as in absolute weight in all age groups. The difference was significant in dry tissue also. When the change was expressed in percentage the greatest effect of T4 was found in 15- and 19-day-old animals. Another experiment followed the effect of only two injections of T4 on BAT to animals of 7 different litters but of the same age, i.e. on day 5 and 6 and euthanized as 7-day-old. In all litters the increase after T4 treatment was significant; the increase in % ranged from 20 to 40% and was influenced by the level in controls. The relative weight in control animals ranged from 620 to 920 mg/100 g BW. This between-litter variance is greater than the effect of T4.(ABSTRACT TRUNCATED AT 250 WORDS)
Adipose Tissue, Brown↗
[Changes in cholesterol and triacylglycerol serum levels in rats during postnatal ontogenesis].
In the serum of young normal rats during the first two months of life the concentrations of triacylglycerols (TG) and of cholesterol (CH) were determined. Low values in both studied parameters found in newborn animals were followed by a marked increase during the first week of life. In comparison with adult animals high values remained during the first five weeks of life. The results are discussed with regard to the high intake of lipids by milk during the period of sucking, as well as from the point of possible mobilization of tissue lipid stores because of the similar trend in the ontogenetic expression of the gene coding the hormone-sensitive lipase (HSL). On the basis of evaluation of the analytical as well as biological variance it was found, that for the level of 50% of confidentiality the serum concentrations of cholesterol should be in the range X +/- 0.26 mmol/l. For the level of 95% the range of values is X +/- 0.67 mmol/l. It is suggested that these results could be used as reference values for serum lipids in the rat during ontogenesis. (Fig. 1, Ref. 21.)
Aging↗
[Short-term administration of increasing doses of thyroxine has a different effect on serum lipids in male rats and in female rats].
The effects of short-term administration of thyroxine (T4) on serum levels of cholesterol, HDL-cholesterol and triacylglycerols were studied on young adult rats. T4 was injected in three different doses, i.e. 125, 250 and 500 micrograms for four days. The results show significant sexual differences. T4 caused a significant decrease in HDL-cholesterol levels in both sexes. The concentration of cholesterol and triacylglycerol decreased only in males, namely after injections of the highest dose of T4. In females the T4 injections caused no effect in the investigated parameters. It is concluded, that also in short-term applications of hormones, the sex may significantly change the results. Presented results support the latest views on specific interrelationship between thyroid hormone and HDL in comparison with other types of LP. (Tab. 2, Ref. 16.).
Animals↗
The development of lipid metabolism. Effect of short-term application of thyroxine on the level of fatty acids and albumin in serum during ontogenesis in rat.
In young rats of different age the effect of short-term administration of thyroxine (T4) on the level of 6 FFA was determined. The concentration of FFA was expressed in mmol/l as well as the molar ratio to serum albumin. The results show that the level of the total FFA and the ratio of saturated to unsaturated (S/U) FFA are high in control animals till the age of 21 days in comparison with adult animals. Administration of T4 caused marked increase in the total FFA in the youngest age group (8-day-old) and the effect increased with age. Differences in the trend of changes in individual FFA were found. In the concentration of myristic acid (C 14:0) a significant increase was found only till the age of 16 days; in the case of palmit-oleic acid the increase was significant in all age groups. T4 caused no significant changes in the values of stearic acid (18:0). When the data were expressed in terms of the molar ratio FFA/albumin, the changes were more pronounced. The peak values found in 16-day-old animals were 33.9 +/- 0.75; they represent a 2-times higher supply of FFA to tissues in comparison with control animals. In this study it was also found that the concentration of serum albumin in newborn animals is low and represents just 57% of adult values. The short-term application of T4 caused no changes in the concentration of serum albumin. The mechanism of T4 action on FFA during ontogenesis was not explained in this study.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The development of lipid metabolism. Changes in the level of fatty acids in serum during postnatal ontogenesis in the rat.
In young rats of 5 different age groups the spectrum (per cent) of 6 FFA was determined. The results show, that palmitic acid (C16:0) represents the main FFA in all age groups; at the end of the first week forms nearly 50 per cent. In adult animals (8-week-old) values decreased to 26 per cent. Similarly, the myristic acid (C14:0) was found highest in suckling animals (10 per cent) and decreased with age. The ratio of saturated to unsaturated FA (S/U) decreased with age. In other animals of 7 different age groups the concentration of total and of individual FFA was investigated. The results were expressed in nmol.l-1. Results showed, that the total concentration of FFA during the first postnatal month is nearly 2-times higher than in adults. The ratio of S/U FFA decreased from 1.81 to 0.85. The concentrations of individual FFA showed different age-dependent trend. Myristic and stearic acids (C14:0 and 18:0) increased with age till the 4th week. The concentrations of palmitic, oleic and linoleic acids were high during the first 3 weeks of age and decreased after weaning. The concentration of palmitate-oleic acid (C16:1) was lowest in all age groups as well as that of palmitic (C 16:0) was always the highest. These results show, that changes in concentration of individual FFA with age are not dependent only on the intake of the milk. (Tab. 3, Fig. 1, Ref. 8).
Aging↗