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Biomedical subjects

Gilbert Reibnegger

Publications and source records attributed to Gilbert Reibnegger.

14 recordsLinked to original sources

[Computer-based training in dermatooncology--a preliminary report comparing electronic learning programs with face-to-face teaching].

BACKGROUND: Electronic media are increasingly used in medical education. The question arises whether tutorial programs are as effective as innovative face-to-face didactic formats. METHODS: 26 students underwent a special dermatooncology course in an integrated undergraduate medical curriculum. One part of the content was acquired face-to-face with emphasis on team learning and mini-lectures; the other part was presented as web-based electronic computer-based training objects. The performance of the students in a subsequent multiple choice test was evaluated. RESULTS: In total, questions referring to computer-based training contents were answered correctly in 90.4 +/- 12.5 %, which was significantly superior to the questions referring to team learning in the face-to-face teaching format (80.6 +/- 13.1 %; p < 0.001). There was, however, a significant correlation between both results for each individual student (r = 0.52; p < 0.01), but there was no correlation between the results obtained for computer-based training or team learning on the one hand, and the overall performance of the individual student on the other. CONCLUSIONS: Though different contents were concerned, our study provides evidence that computer-based training may be more efficient than face-to-face teaching using team learning to communicate dermatooncology contents in an undergraduate medical curriculum.

Austria↗

Interference of 7,8-dihydroneopterin with peroxynitrite-mediated reactions.

By in vitro studies 7,8-dihydroneopterin, which is secreted by macrophages stimulated by interferon-gamma, was reported to be a radical scavenger as well as a prooxidative agent depending on the experimental settings. In this study, we investigated the interference of 7,8-dihydroneopterin with peroxynitrite mediated reactions by different analytical procedures. Luminol chemiluminescence and oxidation of the spin probe 1-hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine induced by peroxynitrite were inhibited by 7,8-dihydroneopterin. On the other hand, we found that 7,8-dihydroneopterin very efficiently inhibits nitration of tyrosine by peroxynitrite. Hydroxylation, however, was rather enhanced than inhibited, suggesting that 7,8-dihydroneopterin reacts in quite different manner with the intermediates generated from peroxynitrite. We provide the first evidence that a pterin radical is formed from a dihydropterin using EPR spectroscopy and 2,2,4-trimethyl-2H-imidazole-1-oxide as a spin trap. We conclude that 7,8-dihydroneopterin while being a weak scavenger of superoxide acts as a very efficient inhibitor of tyrosine nitration induced by peroxynitrite.

Electron Spin Resonance Spectroscopy↗

Quantitative analysis of sinistrin in serum with high-performance liquid chromatography for renal function testing.

Sinistrin, as inulin, is widely used as a marker for renal function testing. A reliable and accurate method with a simple sample preparation for the quantitative determination of sinistrin would be of advantage. We developed a high-performance liquid chromatography (HPLC)-based method with electrochemical detection for the quantitative measurement of sinistrin in serum and plasma. Sample preparation is easy and includes enzymatic removal of glucose, deproteinization, acid hydrolysis of sinistrin, and HPLC separation of fructose. The recovery of sinistrin from serum is the same as that from water and is near 100%. The method presented has a linear range up to 500 mg/L. The results from our method are in agreement with a fully enzymatic quantification (regression coefficient 1.01, coefficient of variation 0.97). Sinistrin concentrations in aqueous solutions can be measured down to 2mg/L with a coefficient of variation of 5.7%. Quantification in serum is primarily limited by its physiological fructose content. The sensitivity of the described method is sufficient for its use in renal function testing. We describe a method for quantification of sinistrin which allows accurate measurements especially at low concentrations and low sample volumes. This laboratory method may be used for obtaining sinistrin pharmacokinetics in renal function testing.

Catalase↗

Modulation of LDL oxidation by 7,8-dihydroneopterin.

Human macrophages stimulated with interferon-gamma generate neopterin and 7,8-dihydroneopterin which interfere with reactive species involved in LDL oxidation. While neopterin was found to have pro-oxidative effects on copper-mediated LDL oxidation, the influence of 7,8-dihydroneopterin is more complex. This study provides detailed information that 7,8-dihydroneopterin reveals both pro-oxidative and anti-oxidative effects on copper mediated LDL oxidation. 7,8-dihydroneopterin inhibited the oxidation of native LDL effectively monitored by (i) formation of conjugated dienes, (ii) relative electrophoretic mobility (EM) and (iii) specific oxidized epitopes. Using minimally oxidized LDL (mi-LDL) or moderately oxidized LDL (mo-LDL) 7,8-dihydroneopterin changed its antioxidative behavior to a strongly pro-oxidative. Incubation of 7,8-dihydroneopterin with native LDL, mi-LDL or mo-LDL in the absence of copper ions showed that formation of conjugated dienes was more increased in mo-LDL than in mi-LDL while no diene formation was observed with native LDL. We suggest that 7,8-dihydroneopterin is a modulator for LDL oxidation in the presence of copper ions depending on the "oxidative status" of this lipoprotein.

Chelating Agents↗

Effect of hemodialysis on the antioxidative properties of serum.

In patients with chronic renal failure undergoing regular hemodialysis (HD), oxidative stress is involved in the development of dialysis-related pathologies. The aim of the study was to measure the effect of HD treatment on the general antioxidative status of serum with special consideration of the specific oxidizability of lipids and proteins. Indicators for the oxidative/antioxidative status of plasma were monitored at the beginning and at the end of a dialysis session on the arterial and venous side of the dialyzer. A decrease in the antioxidant status was accompanied by an increased oxidizability of proteins as well as lipids during HD treatment. During the first passage of the dialyzer, the lag time of lipid oxidation decreased from 114.0+/-19.8 to 81.5+/-18.9 min, the lag time of protein oxidation decreased from 105.0+/-24.6 to 72.9+/-21.3 min and the total antioxidative status decreased from 518+/-24 to 252+/-124 microM trolox equivalents. The carbonyl content of serum proteins was high in patients with end stage renal disease (ESRD) (3.9+/-1.1 vs. 0.9+/-0.1 nmol/mg in controls) but did not change significantly during dialysis procedure. Our data demonstrate that the susceptibility of serum lipids and proteins to oxidative modification is severely increased by HD treatment.

Adult↗

NADH supplementation decreases pinacidil-primed I K ATP in ventricular cardiomyocytes by increasing intracellular ATP.

1 The aim of this study was to investigate the effect of nicotinamide-adenine dinucleotide (NADH) supplementation on the metabolic condition of isolated guinea-pig ventricular cardiomyocytes. The pinacidil-primed ATP-dependent potassium current I(K(ATP)) was used as an indicator of subsarcolemmal ATP concentration and intracellular adenine nucleotide contents were measured. 2 Membrane currents were studied using the patch-clamp technique in the whole-cell recording mode at 36-37 degrees C. Adenine nucleotides were determined by HPLC. 3 Under physiological conditions (4.3 mM ATP in the pipette solution, ATP(i)) I(K(ATP)) did not contribute to basal electrical activity. 4 The ATP-dependent potassium (K((ATP))) channel opener pinacidil activated I(K(ATP)) dependent on [ATP](i) showing a significantly more pronounced activation at lower (1 mM) [ATP](i). 5 Supplementation of cardiomyocytes with 300 micro g ml(-1) NADH (4-6 h) resulted in a significantly reduced I(K(ATP)) activation by pinacidil compared to control cells. The current density was 13.8+/-3.78 (n=6) versus 28.9+/-3.38 pA pF(-1) (n=19; P<0.05). 6 Equimolar amounts of the related compounds nicotinamide and NAD(+) did not achieve a similar effect like NADH. 7 Measurement of adenine nucleotides by HPLC revealed a significant increase in intracellular ATP (NADH supplementation: 45.6+/-1.88 nmol mg(-1) protein versus control: 35.4+/-2.57 nmol mg(-1) protein, P<0.000005). 8 These data show that supplementation of guinea-pig ventricular cardiomyocytes with NADH results in a decreased activation of I(K(ATP)) by pinacidil compared to control myocytes, indicating a higher subsarcolemmal ATP concentration. 9 Analysis of intracellular adenine nucleotides by HPLC confirmed the significant increase in ATP.

Action Potentials↗

Generation of carbon monoxide and iron from hemeproteins in the presence of 7,8-dihydroneopterin.

7,8-Dihydroneopterin and neopterin are secreted by human and primate macrophages after activation by interferon-gamma in a ratio of 2:1. 7,8-Dihydroneopterin is known to suppress radical-mediated processes, but it is also able in the presence of iron ions to generate superoxide radical anion and hydroxyl radicals from molecular oxygen. Effects of 7,8-dihydroneopterin were investigated on (met)myoglobin and (met)hemoglobin. Addition of 7,8-dihydroneopterin to heme proteins in air-saturated solution resulted in dose-dependent cleavage of the porphyrin moiety. The liberation of non-heme iron and carbon monoxide originating from the cleaved porphyrin was quantified. Both were generated at equimolar concentrations with a linear correlation coefficient of 0.9. Addition of ferrous iron significantly accelerated the pteridine-mediated cleaving of the porphyrin. However, the total yield of porphyrin cleaved was controlled by the pterin rather than by the ferrous ion concentration. 7,8-Dihydroneopterin is assumed to reduce the heme iron in intact protein molecules, thereby preparing the conditions for binding of oxygen and carbon monoxide as ligands. Beyond that, it is concluded that hydroxyl radicals might be generated via reduction of molecular oxygen to superoxide anion in the autoxidation process and dismutation to hydrogen peroxide and subsequent Fenton reaction.

Animals↗

End-stage renal failure reduces central clearance and prolongs the elimination half life of remifentanil.

PURPOSE: To evaluate the pharmacokinetics of remifentanil in 13 end-stage renal failure patients compared to matched control patients with normal renal function. METHODS: Remifentanil was infused for 20 min at a rate of 0.1 microg x kg(-1) x min(-1). Serial arterial blood samples (3 mL) were drawn at the start of infusion (zero), five, ten, 15, 20, 22.5, 25, 27.5, 30, 35, 40, 45, 50, 55 and 60 min. Blood samples were immediately preserved with citric acid and chilled on ice. High performance liquid chromatography-tandem mass spectrometry concentration assay was performed using GI 95779B internal standard. RESULTS: A two-compartment pharmacokinetic model provided an adequate fit for individual patient data. There was no difference in the mean +/- SD distribution half life (t1/2) between the renal failure group (1.65 +/- 0.7 min) and the control group (1.58 +/- 0.54 min). There was a significant difference in the central clearance (Cl(c)) and elimination half life (t1/2) ss) between the renal failure group (28 +/- 7 mL x kg(-1) x min(-1) and 18.86 +/- 2.06 min, respectively) and the control group (46.3 +/- 13.8 mL x kg(-1) x min(-1) and 16.35 +/- 2.99 min, respectively). Remifentanil blood concentrations were significantly higher in the renal failure group than in the control group. CONCLUSION: We have demonstrated a significant reduction in the Cl(c) and a prolongation of t1/2 ss of remifentanil in end-stage renal failure patients. While statistically significant, these variations in the pharmacokinetics of remifentanil were clinically modest and may be explained by a reduced volume of distribution in the period following hemodialysis.

Analgesics, Opioid↗

Pitfalls of single-sample determination of renal clearance.

BACKGROUND: Single-sample techniques are widely used for determination of renal clearance by elimination kinetics of radiolabelled marker substances. Frequently, however, formulae for transforming single-time measurement values into estimates of kinetic function, such as renal clearance, are being established exclusively by data reduction methods and are devoid of any physiological meaning. METHODS: Using 11 subjects with normal or impaired renal function, we compared one such method using (99m)Tc-labelled mercaptoacetyltriglycine ((99m)Tc-MAG(3)) for single-sample determination of tubular extraction rates with a more elaborate computer-based system identification technique. This latter method yields measures for glomerular filtration rate as well as effective renal plasma flow based on elimination kinetics of sinistrin and p-aminohippuric acid. RESULTS: When applying the single-sample technique, two of the 11 estimated values for tubular extraction rate were negative, indicating an erroneous analysis of kinetic behaviour. This single-sample method failure was not caused by the marker, but rather by the specific mathematical procedure used for the evaluation. Importantly, evaluation of the same experimental data with a conventional two-sample technique would eliminate the principal mathematical defect and produce physiologically reasonable results, without requiring additional effort. CONCLUSIONS: Our study does not criticize the (99m)Tc-MAG(3) technique per se. Rather, these findings indicate that usage of single-sample techniques for determination of inherently kinetic phenomena may produce incorrect results. Therefore, despite their obvious practical advantages, such simplified methods should be performed with great caution.

Adult↗

Differences of subcutaneous adipose tissue topography between type-2 diabetic men and healthy controls.

Men with noninsulin-dependent diabetes mellitus (type 2 DM) provide a different subcutaneous body fat distribution and a concentration of fatness on the upper trunk compared with healthy subjects. However, subcutaneous fat distribution is always measured in an inaccurate and/or very simplified way (e.g., by caliper), and to date, there exists no study reporting on the exact and complete subcutaneous adipose tissue distribution of type 2 DM men. A new optical device, the LIPOMETER, enables the nonivasive, quick, and safe determination of the thickness of subcutaneous adipose tissue layers at any given site of the human body. The specification of 15 evenly distributed body sites allows the precise measurement of subcutaneous body fat distribution, so-called subcutaneous adipose tissue topography (SAT-Top). SAT-Tops of 21 men with clinically proven type 2 DM (mean age of 57.5 +/- 6.7 years) and 111 healthy controls of similar age (mean age 59.0 +/- 5.4 years) were measured. In this paper, we describe the precise SAT-Top differences of these two groups and we present the multidimensional SAT-Top information condensed in a two-dimensional factor value plot. In type 2 DM men, especially in the upper trunk, SAT-Top is significantly increased (up to +50.7% at the neck) compared with their healthy controls. One hundred eleven of the 132 individuals (84.1%) are correctly classified (healthy or type 2 DM) by their subcutaneous fat pattern by stepwise discriminant analysis.

Adipose Tissue↗

Estimating percentage total body fat and determining subcutaneous adipose tissue distribution with a new noninvasive optical device LIPOMETER.

A newly developed optical device was applied to measure the subcutaneous adipose tissue (SAT) thickness of 20 healthy women and 18 healthy men at specified body sites. These measurements were used to derive equations to estimate percentage total body fat (TBF%). Total body electrical conductivity (TOBEC) was employed as a reference method; caliper techniques and measurements of absorbances of infrared light in fat versus lean tissue were also compared. The LIPOMETER results show good agreement with TOBEC data (r = 0.96). The technique allows the precise determination of the distribution of SAT thickness at specified body sites. The method also permits the construction of profiles of SAT thicknesses, e.g., the profiles are significantly different between women and men. Based on the normal profiles of healthy subjects, patients with proven type-2 diabetes mellitus were also evaluated. The patients showed significantly different profiles. By linear discriminant analysis, classification functions were extracted with good predictive accuracy classification of subjects according to the presence or absence of type-2 diabetes mellitus. The data suggest that measurement of SAT thickness might aid in the diagnosis and/or classification of metabolic disorders. Am. J. Hum. Biol. 12:221-230, 2000. Copyright 2000 Wiley-Liss, Inc.

Journal Article↗

Measurement of subcutaneous adipose tissue topography (SAT-Top) by means of a new optical device, LIPOMETER, and the evaluation of standard factor coefficients in healthy subjects.

The quantification of obesity in respect to subcutaneous adipose tissue and fat distribution is a matter of interest. We recently reported on a new optical device, LIPOMETER, and its ability to measure the thickness of subcutaneous adipose tissue and its advantages compared with other methods. To describe the subcutaneous adipose tissue distribution of the human body in a precise, reproducible, and comparable manner, 15 well-defined body sites distributed from neck to calf on the right body side were used. This set of sites defines subcutaneous adipose tissue topography (SAT-Top). To visualize SAT-Top for subjects or groups, special SAT-Top plots were used. Subcutaneous adipose tissue distribution can be recognized easily with these techniques. SAT-Top of 590 healthy men and women was measured. Factor analysis was used to extract the essential information from these 590*15 intercorrelated single measurements and to provide standard factor coefficients for later applications. As an example of how to use the results of factor analysis, the strong SAT-Top deviation of women with clinically proven type-2 diabetes mellitus (NIDDM) from healthy controls is described. Am. J. Hum. Biol. 12:231-239, 2000. Copyright 2000 Wiley-Liss, Inc.

Journal Article↗

ROC and CART analysis of subcutaneous adipose tissue topography (SAT-Top) in type-2 diabetic women and healthy females.

Women suffering from type-2 diabetes mellitus (NIDDM) show a more android fat pattern than healthy females, but to date no exact determination of their fat distribution differences exists. Measurements at 15 specified body sites with an optical device, the LIPOMETER, provide a subcutaneous adipose tissue topography (SAT-Top) of the individual. SAT-Top of 20 female NIDDM patients and 122 healthy controls was measured. ROC curve analysis was applied to evaluate the discriminative power of each body site and to provide cutoff values. Then a classification tree by the CART algorithm was established, showing SAT-Top differences between the two groups. Best discriminating results were achieved by the neck site (ROC area index = 0.76, sensitivity = 61.3%, specificity = 77.8%), the four sites of the thigh (area indices from 0.71 to 0.76), and a linear combination of all body sites stemming from a previous factor analysis, which provides condensed information of the extremities SAT-Top (area index = 0.80, sensitivity = 80.4%, specificity = 64.6%). The results could be improved by a summary measure of "android fat pattern" (area index = 0.89, sensitivity = 73.6%, specificity =88.3%) and a proportional measure of SAT-distribution, the relative neck (area index = 0.84, sensitivity = 83.0%, specificity = 70.5%). Overall, 136 (95.8%) of the 142 subjects were correctly classified by the classification tree (sensitivity = 75%, specificity = 99.2%). Both methods show the expected increased upper trunk obesity and decreased lower body obesity of NIDDM women compared with healthy females. Am. J. Hum. Biol. 12:388-394, 2000. Copyright 2000 Wiley-Liss, Inc.

Journal Article↗