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Biomedical subjects

Rudolf Poledne

Publications and source records attributed to Rudolf Poledne.

15 recordsLinked to original sources

Proportional odds logistic regression--effective means of dealing with limited uncertainty in dichotomizing clinical outcomes.

Classifying a measurable clinical outcome as a dichotomous variable often involves difficulty with borderline cases that could fairly be assigned either of the two binary class memberships. In such situations the indicated class membership is often highly subjective and subject to, for instance, a measurement error. In other situations the intermediate level of a three-level ordinal factor may sometimes be explicitly reserved for cases which could likely belong to either of the two binary classes. Such indefinite readings are often eliminated from the statistical analysis. In this article we review conceptual and methodological aspects of employing proportional odds logistic regression for a three level ordinal factor as a suitable alternative to ordinary logistic regression when dealing with limited uncertainty in classifying clinical outcome as a binary variable.

Atherosclerosis↗

IL-10 and TNF-beta gene polymorphisms have no major influence on lactate levels after cardiac surgery.

OBJECTIVE: Lactate levels after cardiac surgery are influenced by different proinflammatory (TNF, IL-6, IL-8) and anti-inflammatory (IL-10) cytokines. The goal of the study was to determine the relationship between polymorphism in the IL-10 (-1082G/A) and TNF-beta (+252G/A) genes and lactate levels in patients after cardiac surgery. METHODS: We performed prospective observational study in 168 consecutive adult patients without left ventricle dysfunction undergoing elective coronary artery bypass grafting. Lactic acid levels were documented at five different time points: 10 min after beginning of cardiopulmonary bypass, 40 min after cardiopulmonary bypass termination, and 30 min, 8h, and 16 h after the surgery. Genetic analysis for polymorphism was performed by mismatched polymerase chain reaction and restriction analysis. RESULTS: No association was found between single polymorphism in IL-10 or TNF-beta gene and lactate levels, but the carriers of IL-10/TNF-beta genotype combination +A/GG had significantly different course of lactate levels in time with decrease in lactate (in comparison with increase in other groups) at 8h after the surgery. CONCLUSIONS: IL-10 (-1082G/A) and TNF-beta (+252G/A) gene polymorphisms have a little, yet measurable influence on the time course of changes in lactate levels after cardiac surgery.

Adult↗

The decrease in C-reactive protein concentration after diet and physical activity induced weight reduction is associated with changes in plasma lipids, but not interleukin-6 or adiponectin.

Subclinical inflammation is a risk factor for cardiovascular disease. The mechanisms underlying increased levels of inflammatory markers and their changes in response to weight loss are not fully understood yet. It has been proposed that elevated concentrations of C-reactive protein (CRP) are mediated by cytokines produced in adipose tissue. We investigated the changes in circulating CRP after weight reduction, in relation to parameters relevant to the metabolic syndrome. Forty 25- to 35-year-old obese female volunteers participated in an intervention program of dietary education and supervised physical activity for a period of 9 weeks. Anthropological parameters and biochemical measurements (high-sensitivity CRP [hsCRP], plasma lipoproteins, interleukin 6 [IL-6], adiponectin) were analyzed before and after the intervention. Body mass index decreased by more than 7% from 31.5 +/- 4.1 to 29.1 +/- 3.9. Plasma free fatty acid (FFA) concentrations decreased by 30%, high-density lipoprotein cholesterol increased by 8%, and fasting insulin concentrations decreased by 15%. There were no significant changes in either low-density lipoprotein cholesterol or triacylglycerol concentrations. Subcutaneous and visceral adipose tissue mass decreased by 12% and 18%. High-sensitivity CRP concentrations decreased by 30%; however, mean plasma IL-6 and adiponectin concentrations remained unchanged. In linear regression analysis, the changes in plasma hsCRP concentrations were associated with baseline hsCRP concentration, change in triacylglycerols and FFA concentrations, and in waist circumference. The decrease in hsCRP concentration after weight reduction does not appear to be mediated by decreases in circulating IL-6 or adiponectin concentrations; however, change in hsCRP concentration is related to changes in waist circumference and lipid metabolism, reflected by plasma triacylglycerol and FFA levels.

Adiponectin↗

Do lipids contribute to the lack of cardio-protective effect of binge drinking: alcohol consumption and lipids in three eastern European countries.

AIMS: The cardio-protective effect of moderate alcohol consumption is partly mediated by HDL cholesterol. However, epidemiological studies suggest that binge drinking may not be associated with reduced risk of heart disease; a possible explanation is that the relationship of blood lipids with binge drinking is different from that with moderate intake. We investigated this hypothesis in a population study in three eastern European countries. METHODS: We conducted a cross-sectional study in random population samples in Novosibirsk (Russia), Krakow (Poland) and Karvina (Czech Republic). A sub-sample of 282 men aged 45-64 years who provided a fasting blood sample were analysed. Annual alcohol intake and the frequency of heavy binge drinking (> or =140 g of ethanol per session) were estimated from a graduated frequency questionnaire. RESULTS: Annual intake of alcohol was positively associated with total and HDL cholesterol. After controlling for annual intake, the frequency of heavy binge drinking was associated with increased concentrations of total and HDL cholesterol. By combining annual intake and drinking pattern, we found that men consuming >8 l of alcohol per year who had a heavy binge at least once a month had the mean total, HDL and LDL cholesterol 1.69 (SE 0.35), 0.61 (0.11) and 0.97 (0.34) mmol/l, respectively, higher than non-drinkers; this resulted in more favourable ratios of total and LDL cholesterol relative to HDL cholesterol in frequent heavy bingers. Triglycerides were not related to alcohol intake or binge drinking. CONCLUSIONS: Blood lipids do not seem to explain the apparent lack of the cardio-protective effect of binge drinking reported in epidemiological studies.

Alcoholic Intoxication↗

Sex-specific effect of APOAV variant (Val153>Met) on plasma levels of high-density lipoprotein cholesterol.

The importance of the APOAV gene for the determination of plasma triglyceride levels has been suggested by creations of transgenic and knockout mice and confirmed in population studies. We examined whether the newly detected APOAV variant is associated with plasma lipid levels and risk of myocardial infarction (MI). APOAV polymorphism (Val153>Met) was genotyped in 1191 males and 1368 females representatively selected from the Czech population. Lipid levels were analyzed in 1997 and 2001 in all individuals. Subsequently, we have analyzed the genotype frequencies of APOAV polymorphism in 435 male patients with MI. Val153>Met variation in the APOAV gene affects the plasma high-density lipoprotein cholesterol levels showing a higher level in Val/Val homozygotes than in Met carriers in both years (1.51 +/- 0.36 and 1.52 +/- 0.37 mmol/L compared with 1.42 +/- 0.33 and 1.39 +/- 0.35 mmol/L, P < .01). This association has been observed in females but not in males. Other analyzed lipid parameters (total cholesterol, low-density lipoprotein cholesterol, and triglycerides) have not been associated with APOAV Val153>Met variant. In a group of patients with MI, the frequency of the Met153 carriers was not significantly different from the male population sample (6.5% vs 6.4%). Val153>Met variation in the APOAV gene plays a sex-specific role in genetic determination of plasma high-density lipoprotein cholesterol levels, but does not influence risk of MI in males.

Adult↗

Triglyceride-lowering effect of respiratory uncoupling in white adipose tissue.

OBJECTIVE: Hypolipidemic drugs such as bezafibrate and thiazolidinediones are known to induce the expression of mitochondrial uncoupling proteins (UCPs) in white adipose tissue. To analyze the potential triglyceride (TG)-lowering effect of respiratory uncoupling in white fat, we evaluated systemic lipid metabolism in aP2-Ucp1 transgenic mice with ectopic expression of UCP1 in adipose tissue. RESEARCH METHODS AND PROCEDURES: Hemizygous and homozygous transgenic mice and their nontransgenic littermates were fed chow or a high-fat diet for up to 3 months. Total TGs, nonesterified fatty acids, and the composition of plasma lipoproteins were analyzed. Hepatic TG production was measured in mice injected with Triton WR1339. Uptake and the use of fatty acids were estimated by measuring adipose tissue lipoprotein lipase activity and fatty acid oxidation, respectively. Adipose tissue gene expression was assessed by quantitative reverse transcriptase-polymerase chain reaction. RESULTS: Transgene dosage and the high-fat diet interacted to markedly reduce plasma TGs. This was reflected by decreased concentrations of very-low-density lipoprotein particles in the transgenic mice. Despite normal hepatic TG secretion, the activity of lipoprotein lipase in epididymal fat was enhanced by the high-fat diet in the transgenic mice in a setting of decreased re-esterification and increased in situ fatty acid oxidation. DISCUSSION: Respiratory uncoupling in white fat may lower plasma lipids by enhancing their in situ clearance and catabolism.

Adipose Tissue↗

Limitations of non-invasive endothelial function assessment by brachial artery flow-mediated dilatation.

A non-invasive technique using high-frequency ultrasound brachial artery imaging to assess endothelium-dependent flow-mediated vasodilatation is a widely used test, but interpretation of results is not consistent. This study was designed to assess the method of non-invasive endothelial function determination of a brachial artery. Endothelial function was assessed by two physicians in 18 young, healthy volunteers. Each volunteer was examined by both physicians on the same day using an identical protocol; a second assessment was carried out at an interval of 6-7 days. When comparing arterial dilatation at first and second measurements by one physician, there were no statistically significant differences (first physician: 5.95 +/- 2.93% versus 7.63 +/- 4.3%; P = 0.21; second physician: 4.23 +/- 1.6% versus 4.94 +/- 2.69%; P = 0.22). Further, we found statistically significant differences in artery dilatation when comparing measurements made separately by both physicians on the same day (5.95 +/- 2.93% versus 4.23 +/- 1.6%; P = 0.03, and 7.63 +/- 4.3% versus 4.94 +/- 2.69%; P = 0.003). Our results suggest a large inter-individual variability of measurements within the whole group, if made on the same day and at the same time by two physicians. On the contrary, no significant differences were noted when comparing measurements of the whole group by the one physician at an interval of 1 week. It can be concluded that the degree of brachial artery flow-mediated dilatation is difficult to evaluate on the basis of a predefined cut-off point as a single-measurement screening test.

Adult↗

APOAV (T-1131>C) variant has no effect on mother's height in a large population study.

The important role of APOAV gene T-1131>C variant in determination of plasma triglyceride levels has been proved on many population studies. Recently, associations between C-1131 allele and higher mother's height as well as with longer fetal birth length were suggested. In 1,305 females, aged between 28 and 67 years and having at least one child, we have analyzed a putative association between T-1131>C APOAV variant (analyzed by PCR and restriction analysis) and body height. Mother's body height did not differ between T/T homozygotes (N = 1093, 162.5 +/- 6.5 cm) and C allele carriers (N = 212, 162.1 +/- 6.4 cm). Thus we have failed to confirm, that mothers with APOAV C-1131 allele are higher than T/T-1131 homozygotes.

Comment↗

Genetic analysis of APOAV polymorphisms (T-1131/C, Ser19/Trp and Val153/Met): no effect on plasma remnant particles concentrations.

BACKGROUND: APOAV is newly described protein, which plays a crucial role in the determination of plasma triglyceride (TG) levels. Remnant lipoproteins (RLPs) result from partial catabolised TG-rich particles. Elevated levels of RLP are associated with atherosclerosis, and they are a predictor of coronary events in patients with coronary artery disease. METHODS: We have evaluated the influence of APOAV polymorphisms (T-1131/C, Ser19/Trp and Val153/Met were measured by PCR and restriction analysis) on plasma levels of RLP-cholesterol and RLP-TG in 285 unrelated representative selected individuals (131 men and 154 women) aged 33-72 years. RESULTS: RLP-cholesterol and RLP-TG levels were not significantly influenced by the APOAV variants either in whole population or in males and females, if analyzed separately. CONCLUSIONS: We conclude that variations T-1131/C, Ser19/Trp and Val153/Met in the APOAV gene have no effect on plasma levels of remnant particles.

Adult↗

Polymorphisms in CYP-7A1, not APOE, influence the change in plasma lipids in response to population dietary change in an 8 year follow-up; results from the Czech MONICA study.

OBJECTIVES: To evaluate the influence of variation in the genes for apolipoprotein E (APOE; epsilon2, epsilon3, epsilon4) and cholesterol-7alpha hydroxylase (CYP-7A1; -204A-->C) on plasma lipid level changes. DESIGN AND METHODS: 131 males for whom dietary composition markedly changed and total cholesterol decreased (from 6.21 +/- 1.31 mmol/L in 1988 - 5.43 +/- 1.06 mmol/L in 1996) over an 8 yr follow-up study. Polymorphisms were investigated using PCR. RESULTS: APOE genotype influenced plasma total and LDL cholesterol, with carriers of the epsilon4 having the highest and epsilon2 carriers the lowest levels, this reached borderline significance for cholesterol in 1988 (p = 0.06) and strongly affected the 1996 levels of LDL cholesterol (p = 0.008). However, APOE did not influence the change in these measures over time. In contrast, the CYP-7A1 -204A-->C polymorphism did not affect lipid measures per se but was strongly associated with a decrease in plasma total cholesterol [AA -0.38 (+/- 0.20) mmol/L, AC -0.65 +/- (0.08), CC -1.33 (+/- 0.3) mmol/L, p = 0.01] over the 8 yr time period. CONCLUSIONS: Variation in the CYP-7A1 gene may play an important role in an individual's sensitivity to dietary composition.

Adult↗

Comparison of the effects of atorvastatin or fenofibrate on nonlipid biochemical risk factors and the LDL particle size in subjects with combined hyperlipidemia.

BACKGROUND: Combined hyperlipidemia (CH) is an increasingly prevalent risk factor for premature heart disease, and its treatment is troublesome. The aim of this study was to compare the effects of atorvastatin and fenofibrate on nonlipid biochemical risk factors and the low-density lipoprotein (LDL) particle size in subjects with CH. METHODS: Twenty-nine middle-aged men with CH were randomly assigned to open-label therapy with atorvastatin (10 mg daily) or micronized fenofibrate (200 mg daily); they were sequentially treated with both drugs, with crossover of medication after 10 weeks. RESULTS: Atorvastatin was more efficient in the reduction of total cholesterol, whereas fenofibrate was more efficient in the reduction of triglycerides. Only atorvastatin led to a significant reduction of LDL cholesterol and apolipoprotein B. Only fenofibrate increased high-density lipoprotein cholesterol. Neither drug influenced lipoprotein(a). Mean LDL particle size increased both after fenofibrate (3.08%) and atorvastatin (1.77%). Fenofibrate increased serum homocysteine (HCY) by 36.5%. Atorvastatin had no effect on HCY. Only atorvastatin increased fibrinogen by 17.4%. Only fenofibrate reduced C-reactive protein by 51.7%. Neither drug influenced HOMA (homeostasis model assessment) index of insulin resistance. The plasma level of thiobarbituric acid reactive substances, an index of oxidative stress, decreased after both treatments. CONCLUSIONS: Both atorvastatin and fenofibrate had similar beneficial effects on LDL particle size and on oxidative stress. The effects of both drugs on other parameters such as triglycerides, total and high-density lipoprotein cholesterol, fibrinogen, or HCY differed significantly. These differences, together with the risk profile of a patient, should be considered during selection of a particular lipid-lowering modality.

Apolipoproteins B↗

Polymorphisms in the lipopolysaccharide-binding protein and bactericidal/permeability-increasing protein in patients with myocardial infarction.

Gram-negative bacterial infection, namely Chlamydia pneumoniae has been recently discussed as a risk factor for myocardial infarction. The lipopolysaccharide-binding protein (LBP) and the bactericidal/permeability-increasing protein (BPI) play a role in the processes leading to recognition and neutralisation of the Chlamydia pneumoniae and their endotoxins lipopolysaccharides (LPS). LPS interact with plasma LBP, and LBP-LPS complex activates monocytes/macrophages, which can influence the atherosclerotic process. BPI is cytotoxic for Gram-negative bacteria and BPI-LPS complexes do not activate monocytes. We have analysed the polymorphisms in the LBP gene (Gly98-->Cys; Pro436-->Leu) and BPI gene (Lys216-->Glu; PstI polymorphism in intron-5; G545-->C) in 313 patients after myocardial infarction (MI) and in 302 control individuals. Genotype frequencies in the LBP gene and BPI gene did not differ between MI patients and control individuals. Our findings suggest that LBP and BPI polymorphisms do not influence the risk of MI.

Acute-Phase Proteins↗

Is the CD14 receptor gene a marker for smoking dependence?

BACKGROUND: The CD14 receptor is a myeloid cell-specific receptor, which plays a role in host defense and cell stimulation. CD14 positive cells have been detected in lung, and also in brain, and the CD14 receptor is thought to play a role in asthma and allergy reactions. C-159-->T polymorphism in the promoter of the CD14 gene has been associated with myocardial infarction, but not in all studies. Our goal was to establish whether this polymorphism is associated with some of the risk factors of MI. MATERIAL/METHODS: With PCR and subsequent restriction analysis we evaluated C-159-->T polymorphism in the CD14 gene in 135 representative selected male Caucasians. RESULTS: We detected a significantly higher frequency of T/T homozygotes (p<0.025) in subjects who had never smoked (15 of 60, 25.0%) as compared to smokers and past smokers (6 of 75, 8.0%). CONCLUSIONS: The C-159-->T polymorphism in the CD14 gene could be a genetic marker associated with smoking dependence, but confirmation in a large population study is necessary.

Alleles↗