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Biomedical subjects

G Kirchner

Publications and source records attributed to G Kirchner.

At least 19 recordsLinked to original sources
PubMed2006

Ecological half-lives of 90Sr and 137Cs in terrestrial and aquatic ecosystems.

This paper describes the long-term behaviour of (90)Sr and (137)Cs in foods, feeds and a variety of environmental media. The long-term behaviour is quantified by means of the ecological half-life which integrates all processes that cause a decrease of activity in a given medium such as leaching, fixation and erosion. A large number of long-term time series of concentrations of radiocaesium and radiostrontium in these media have been identified and re-evaluated using a standardised statistical procedure to establish reference data sets of ecological half-lives. By example of undisturbed soils and marine water bodies it is shown that the ecological half-life concept is questionable if the distribution of the radionuclide of interest within the medium studied is non-uniform and if mixing and transport processes within this medium, therefore, are of considerable importance during the time period of observation.

Animals↗
PubMed2004

Modelling the vertical distribution of radionuclides in soil. Part 1: the convection-dispersion equation revisited.

The convective-dispersive transport and linear sorption model is discussed for the vertical migration of radionuclides in soil. An alternative procedure of solving the corresponding system of partial differential equations is presented as well as the special solution for the pulse-like fallout initial condition. Idealizations and simplifications of the model and properties of the solution are discussed. The model is fitted to a set of 528 measured radionuclide soil profiles and the resulting model parameters, apparent convection velocity v and apparent dispersion constant D, are evaluated statistically. Typical orders of magnitude of the velocities and the diffusion constants of Chernobyl-134Cs are 0.3 cm/year and 0.3 cm2/year, respectively. The mobilities of the radionuclides are ranked as 137Cs (global fallout) < 134Cs < 106Ru, 125Sb. Significant regional differences (related to different soils and geological properties below ground) of v and D exist. These analyses also indicate that v and D are not mere fitting parameters, but can be given a real physical interpretation. While in most cases, the convection-dispersion equation (CDE) model produces good descriptions for near-surface soil layers, potentially important limitations are its failure to describe "young" profiles shortly after fallout.

Antimony↗
PubMed2004

[New concepts in ultrasound education in gastroenterology by simulator training].

Ultrasound is one of the most important imaging methods in medicine. However, ultrasound education is complicated by varying quantities and qualities of specific pathologies resulting from distinct patient collectives. Furthermore, under current clinical conditions ultrasound educators as well as trainees frequently lack the time necessary for a sufficient ultrasound education. Finally, current ultrasound education materials including "gold standard" images are not ideally suited for teaching scanning three-dimensional pathologies. In a direct cross over study we recently proved, that the ultrasound simulator we developed simulated the real patient examination reliably and reproducibly. By using this simulator as well in the classical beginner and advanced level courses as in focused courses of abdominal emergencies for instance, ultrasound trainees are able to practice scanning of well defined pathologies under realistic conditions, which has not been possible before. Furthermore, the ultrasound simulator is well suited for a structured ultrasound training in single hospitals as well as in continuous medical education. Finally, objective, standardized ultrasound quality control has become possible with the simulator.

Computer Simulation↗
PubMed2003

Simulation of abdomen sonography. Evaluation of a new ultrasound simulator.

AIM: We developed and evaluated a simulator for the sonography of the abdomen in order to improve the teaching quality in sonography training. METHOD: Eleven medicine residents who had received 4 to 12 months full time sonography training performed ultrasound examinations of the right upper quadrant in 5 consecutive patients and in 5 simulator cases. The correctness of their findings and the time required for the examinations were measured. The subjective confidence in their findings and the handling of the ultrasound machines were rated on a visual analogue scale. RESULTS: During patient ultrasound examination 75 % (SEM 9%) of all pathologic findings were recognized by the residents, whereas 71 % (SEM 8%) of the pathologies of the simulator cases were found. This minimal difference was not significant in the paired, two sided t-test (p = 0.15). Severe pathologies did not escape detection. The time required for patient examination(10.57 min, SEM 3.25 min) was not significantly different (p = 0.53) to the time required for the simulator cases (9.59 min, SEM 2.98 min). The subjective confidence in the sonographic findings did not differ significantly (p = 0.39) between the real patient situation (68%, SEM 6%) and the simulation (64%, SEM 12 %). Only the handling of the ultrasound machines was judged to be significantly better (p=0.008) than the simulator (74%,SEM 7% vs. 61 %, SEM 12%). CONCLUSION: In this first direct crossover comparison between real patient sonography and simulator based scanning we proved that the simulator we developed simulates the real patient examination reliably and reproducibly.

Abdomen↗
PubMed2002

The potential of lichens as long-term biomonitors of natural and artificial radionuclides.

Lichens were used as biomonitors of Chernobyl fallout 137Cs, of cosmogenic 7Be and of radioactive members of the natural uranium and thorium decay chains. Samples were taken from two locations in France, including lichens sampled at different distances of a coal fired power plant and close to a uranium ore processing waste disposal site. All samples were analyzed gamma-spectrometrically after equilibrium concentrations of short-lived isotopes had been attained. Activity concentrations of the members of the uranium and thorium decay chains in Parmelia sulcata sampled 1994 decrease with distance from the plant, whereas in lichens taken at the waste disposal site a decrease with time was observed. Comparison of 7Be activity concentrations measured in lichens with atmospheric deposition rates confirms that P. sulcata can be used as a quantitative biomonitor of radioactive trace substances. Retention half-lives calculated with a simple one-compartment model are 2.6 +/- 1.2 years for cesium, which was detected in all samples even more than a decade after the Chernobyl accident, and of 0.7 (+/- 0.1) to 3.3 (+/- 0.7) years for lead. Consequences of our results for model identifiability and parameter estimation of a two-compartment model are discussed.

Environmental Monitoring↗
PubMed2001

Comparative study analyzing effects of sirolimus-cyclosporin and sirolimus-tacrolimus combinations on bile flow in the rat.

The new immunosuppressive agent sirolimus is combined in transplant patients with the cholestatic substances cyclosporin and tacrolimus. Nothing is known about possible cholestatic effects of these combinations. Therefore, we compared their effects on bile flow and on important bile parameters in an acute bile fistula model in rats. Cyclosporin reduced bile flow, biliary excretion of bile salts, cholesterol, and GSH to 20-40% of basal values. Sirolimus decreased bile flow to 50% and excretion of GSH to 30% of the initial conditions but had no effect on cholesterol and bile salt excretion. In contrast, tacrolimus increased bile flow to 120% and GSH excretion to 220% of the basal levels. Sirolimus/cyclosporin decreased bile flow and bile parameters to the same extent as cyclosporin alone. Sirolimus/tacrolimus reversed sirolimus-induced reduction of bile flow and GSH excretion and resulted in a normal bile salt and cholesterol excretion, thus it may be the better alternative in cholestatic patients.

Animals↗
PubMed2000

Primary porcine enterocyte and hepatocyte cultures to study drug oxidation reactions.

1. Primary porcine hepatocytes and enterocytes were isolated and cultured in Williams' E medium for up to 10 days to investigate potential organ differences in the metabolism of the immunosuppressive compound tacrolimus (FK 506) and of two investigational drugs (KC11346 and KC12291). Using LC-MS (FK506) and HPLC-FL (KC 11346/12291) a number of metabolites with identical mass and/or identical retention time could be detected. 2. In the case of tacrolimus hepatocytes and enterocytes produced the same spectrum of metabolites, e.g. bisdemethyl-tacrolimus, demethyl-tacrolimus, demethyl-hydroxy-tacrolimus and hydroxy-tacrolimus, albeit at varying intensities. 3. Treatment of enterocyte cultures with dexamethasone increased the overall metabolite formation very significantly (up to 36 fold). 4. The metabolism of tacrolimus was also studied with preparations of insect cells, that express specifically high levels of individual human cytochrome P450 (CYP) isoenzymes. All metabolites could be generated with microsomal preparations specifically expressing CYP3A4, but hydroxy-tacrolimus was exclusively produced by CYP3A5. 5. In the case of the investigational drugs KC 11346 and KC 12291 only three metabolites were formed by cultured enterocytes whereas hepatocytes produced 10 and 20 metabolites, respectively. 6. When assessed at the protein level CYP1A and CYP3A were expressed in cultures of porcine enterocytes for up to 10 days but porcine hepatocytes expressed additionally CYP2C9/10. 7. In conclusion, primary enterocytes and hepatocytes can be successfully cultured for several days while maintaining mono-oxygenase activity and may therefore be used as a tool for studying intestinal and hepatic metabolism.

Animals↗
PubMed2000

Community acquired diarrhea--the incidence of Astrovirus infections in Germany.

Astroviruses are increasingly recognized as a cause of human gastroenteritis. Electron microscopy (EM) has been considered the "gold standard" method for diagnosis, but this approach is limited to a few laboratories. We evaluated a commercial enzyme immunoassay (EIA) (IDEIA Astrovirus, DAKO Diagnostika, Hamburg, Germany) for the direct detection of antigen in fecal samples. In comparison to EM, the assay scored 100% in sensitivity and specificity (n = 213; 26 positive samples) and reacted with strains representing all known serotypes. Over an 11-month period 4,211 stool samples from unselected German patients suffering from acute gastroenteritis were examined. Etiologically responsible microorganisms were found in 13.0% of cases, with astrovirus the third most common pathogen (1.2%) behind Salmonella spp. (2.9%) and Rotavirus (2.5%), representing 13.5% of all positive specimens. Norwalk-like viruses (NLV), fungi, and protozoa were not tested. In infants of < 2 years of age (n = 458) the incidence of astrovirus infection was significantly higher (2.8%) compared to children of 2-7 years of age (n = 578; 1.7%) and those of > 7 years of age (n = 3,175; 0.9%). The frequency revealed a peak in winter (mean November-February: 2.0% versus other months: 0.8%).

Adolescent↗
PubMed2000

Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin.

In an in vitro study, we compared the cytochrome P450 (CYP)-dependent metabolism and drug interactions of the acid and lactone forms of the 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitor atorvastatin. Metabolism of atorvastatin acid and lactone by human liver microsomes resulted in para-hydroxy and ortho-hydroxy metabolites. Both substrates were metabolized mainly by CYP3A4 and CYP3A5. Atorvastatin lactone had a significantly higher affinity to CYP3A4 than the acid (K(m): para-hydroxy atorvastatin, 25.6 +/- 5.0 microM; para-hydroxy atorvastatin lactone, 1.4 +/- 0.2 microM; ortho-hydroxy atorvastatin, 29.7 +/- 9.4 microM; and ortho-hydroxy atorvastatin lactone, 3.9 +/- 0.2 microM). Compared with atorvastatin acid, CYP-dependent metabolism of atorvastatin lactone to its para-hydroxy metabolite was 83-fold higher [formation CL(int) (V(max)/K(m)): lactone 2949 +/- 3511 versus acid 35.5 +/- 48.1 microl. min(-1). mg(-1)] and to its ortho-hydroxy metabolite was 20-fold higher (CL(int): lactone 923 +/- 965 versus acid 45.8 +/- 59. 1 microl. min(-1). mg(-1)). Atorvastatin lactone inhibited the metabolism of atorvastatin acid by human liver microsomes with an inhibition constant (K(i)) of 0.9 microM while the K(i) for inhibition of atorvastatin by atorvastatin lactone was 90 microM. Binding free energy calculations of atorvastatin acid and atorvastatin lactone complexed with CYP3A4 revealed that the smaller desolvation energy of the neutral lactone compared with the anionic acid is the dominant contribution to the higher binding affinity of the lactone rather than an entropy advantage. Because atorvastatin lactone has a significantly higher metabolic clearance and the lactone is a strong inhibitor of atorvastatin acid metabolism, it can be expected that metabolism of the lactone is the relevant pathway for atorvastatin elimination and drug interactions. We hypothesize that most of the open acid metabolites present in human plasma are generated by interconversion of lactone metabolites.

Atorvastatin↗
PubMed1999

Results after Norwood procedure and subsequent cavopulmonary anastomoses for typical hypoplastic left heart syndrome and similar complex cardiovascular malformations.

OBJECTIVE: From October 1989 to June 1998, 60 patients have undergone the Norwood procedure (stage I) at our institution. The results of the staged surgical reconstruction and risk factors were analysed. Typical hypoplastic left heart syndrome (HLHS) and complex lesions with aortic hypoplasia were compared with each other. PATIENTS: Typical HLHS: N = 48, median age 15 days (5-190 days), median weight 3.6 kg (2.6-5.3 kg). Complex lesions (dominant left ventricle): N = 12, median age 59 days (10-884 days), median weight 3.4 kg (2.4-12 kg). RESULTS: Typical HLHS: The stage-I hospital survival was 73% (35/48). It improved from 60% (95% confidence interval: 49-71%) during 1989-1994 to 91% (95% CI: 81-100%) during 1997-1998. Seven patients were lost late. The right ventricular end diastolic diameter (P = 0.015), shortening fraction (P = 0.027), and the presence of an obstructed pulmonary venous return (P = 0.0032) were significant risk factors. 23 children underwent stage-II operation with four (17%) deaths. All survivors experienced an improvement of their statomotoric development. Stage-III operation was performed in 13 patients with no hospital death. Follow up after stage-III procedure was 7 months to 7 years. 4 year actuarial survival, including hospital mortality and deaths at subsequent stages, improved from 28% (95% CI: 18-38%) during 1989-1994 to 58% (95% CI: 48-68%) during 1994-1997. No patient had signs of myocardial insufficiency. Complex lesions: Stage-I hospital survival was 83% (10/12) with no late death. Stage-II was performed in 8 and stage-III in 6 patients with no death respectively. CONCLUSION: In typical HLHS the results have improved over time. Both size and function of the right ventricle determined significantly stage-I survival. An early operation prevents the natural progression of pulmonary blood flow and may weaken all three risk factors. Patients with complex lesions seemed to have better chances of surviving the early postoperative period. The multistage reconstructions have become a realistic option for patients with HLHS and similar lesions, regardless of the morphologic subtype or diminutiveness of the aorta, and lead to an acceptable quality of life.

Abnormalities, Multiple↗
PubMed1999

Small intestinal metabolism of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor lovastatin and comparison with pravastatin.

We compared the intestinal metabolism of the structurally related 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors lovastatin and pravastatin in vitro. Human small intestinal microsomes metabolized lovastatin to its major metabolites 6'beta-hydroxy (apparent K(m) = 11.2 +/- 3.3 microM) and 6'-exomethylene (apparent K(m) = 22.7 +/- 9.0 microM) lovastatin. The apparent K(m) values were similar for lovastatin metabolism by human liver microsomes. 6'beta-Hydroxylovastatin formation by pig small intestinal microsomes was inhibited with the following inhibition K(i) values: cyclosporine, 3.3 +/- 1.2 microM; ketoconazole, 0.4 +/- 0.1 microM; and troleandomycin, 0.8 +/- 0.9 microM. K(i) values for 6'-exomethylene lovastatin were similar. Incubation of pravastatin with human small intestinal microsomes resulted in the generation of 3'alpha,5'beta, 6'beta-trihydroxypravastatin (apparent K(m) = 4560 +/- 1410 microM) and hydroxypravastatin (apparent K(m) = 5290 +/- 1740 microM). In addition, as in the liver, pravastatin was metabolized in the small intestine by sulfation and subsequent degradation to its main metabolite 3'alpha-iso-pravastatin. It was concluded that lovastatin is metabolized by cytochrome P-450 3A enzymes in the small intestine. Compared with lovastatin, the cytochrome P-450-dependent intestinal intrinsic clearance of pravastatin was >5000-fold lower and cannot be expected to significantly affect its oral bioavailability or to be a significant site of drug interactions.

Animals↗
PubMed1999

Comparison of cytochrome P-450-dependent metabolism and drug interactions of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors lovastatin and pravastatin in the liver.

In an in vitro study, the cytochrome P-450 3A (CYP3A)-dependent metabolism and drug interactions of the 3-hydroxy-3-methylglutaryl-Co A reductase inhibitors lovastatin and pravastatin were compared. Lovastatin was metabolized by human liver microsomes to two major metabolites: 6'beta-hydroxy [Michaelis-Menten constant (Km): 7.8 +/- 2.7 microM] and 6'-exomethylene lovastatin (Km,10.3 +/- 2.6 microM). 6'beta-Hydroxylovastatin formation in the liver was inhibited by the specific CYP3A inhibitors cyclosporine (Ki, 7.6 +/- 2.3 microM), ketoconazole (Ki, 0.25 +/- 0.2 microM), and troleandomycin (Ki, 26.6 +/- 18.5 microM). Incubation of pravastatin with human liver microsomes resulted in the generation of 3'alpha,5'beta, 6'beta-trihydroxy pravastatin (Km, 4,887 +/- 2,185 microM) and hydroxy pravastatin (Km, 20,987 +/- 9,389 microM). The formation rates of 3'alpha,5'beta,6'beta-trihydroxy pravastatin by reconstituted CYP3A enzymes were (1,000 microM pravastatin) 1.9 +/- 0.6 pmol.min-1.pmol CYP3A4 and 0.06 +/- 0.04 pmol.min-1.pmol CYP3A5, and the formation rates of hydroxy pravastatin were 0.12 +/- 0.02 pmol.min-1.pmol CYP3A4 and 0.02 +/- 0.004 pmol.min-1.pmol CYP3A5. The specific CYP3A inhibitors cyclosporine, ketoconazole, and troleandomycin significantly inhibited hydroxy pravastatin formation by human liver microsomes, but only ketoconazole inhibited 3'alpha, 5'beta,6'beta-trihydroxy pravastatin formation, suggesting that other CYP enzymes are involved in its formation. It is concluded that, compared with lovastatin [CLint formation 6'beta-hydroxylovastatin (microl.min-1.mg-1): 199 +/- 248, 6'-exomethylene lovastatin: 138 +/- 104)], CYP3A-dependent metabolism of pravastatin [CLint formation 3'alpha,5'beta, 6'beta-trihydroxy pravastatin (microl.min-1.mg-1): 0.03 +/- 0.03 and hydroxy pravastatin: 0.02 +/- 0.02] is a minor elimination pathway. In contrast to lovastatin, drug interactions with pravastatin CYP3A-catalyzed metabolism cannot be expected to have a clinically significant effect on its pharmacokinetics.

Biotransformation↗
PubMed1998

Accumulation of 210Pb, 226Ra and radioactive cesium by fungi.

Fungi sampled in three areas in France were analyzed by gamma-spectrometry for their concentrations of 134Cs, 137Cs, 210Pb and 226Ra. In most of the samples radioactive cesium was detected with a maximum of 2860 Bq kg-1 (dry wt.). Activity concentrations of 210Pb were in the range < 1.76-36.5 Bq kg-1 (dry wt.). Activity concentrations of 226Ra were consistently lower, often by one order of magnitude. Models are developed to estimate the contributions of atmospheric 210Pb deposited onto the fruit bodies to the measured 210Pb concentrations and of the uptake of 222Rn soluted in soil pore water which subsequently decays into 210Pb. It is shown that both pathways are of only minor importance. Comparison with the soil-mushroom concentration ratios of stable lead, which were determined for some of the samples, confirmed that 210Pb in mushrooms mainly originates from direct uptake of 210Pb present in the soil. Despite of the high concentrations of 137Cs detected in most of the mushrooms, radiation doses to individuals due to mushroom consumption are dominated by 210Pb for the majority of the edible mushrooms sampled.

Agaricales↗
PubMed1998

Morphological and molecular characterization of human gastric mucous cells in long-term primary culture.

A primary cell culture of human gastric mucous cells was developed using enzymatic treatment of surgically obtained gastric mucosal specimens. Preferential attachment of gastric mucous cells during a preincubation step resulted in the enrichment of mucous cells [over 90% stained with periodic acid-Schiff (PAS) and mucin-type lectins] in the primary cell culture. Gastric mucous cells could be maintained in culture for 10 days. DNA synthesis peaked during the first 2 days in culture (8+/-1% bromodeoxyuridine-positive cells). During the entire culture period gastric mucous cells released high-molecular-weight glycoproteins into the medium, as determined by gel chromatography on a Sepharose CL-4B column and by metabolic labelling with [14C]-N-acetylglucosamine. Gastric mucin was verified by gas chromatographic analysis of the carbohydrate composition and fractionation of the void-volume fraction by density gradient centrifugation. Determination of the terminal glycosylation of the secreted glycoproteins by a lectin-ELISA revealed that there was a high quantity of alpha-l-fucose. Prostaglandin E2 significantly stimulated glycoprotein secretion during the entire cultivation period by 29-60%. Analysis of mucin-encoding MUC mRNA expression by reverse transcriptase polymerase chain reaction revealed that gastric mucous cells predominantly express MUC1 and MUC5AC, and to a lesser extent MUC6, which reflects the expression pattern obtained following analysis of biopsied samples of gastric mucosa. This primary cell culture model enables the regulation of mucin secretion and mucin gene expression in man to be investigated.

Cells, Cultured↗
PubMed1998

Modeling the migration of fallout radionuclides in soil using a transfer function model.

A stochastic model for transport of radionuclides in soil is presented. It is based on probability density functions of solute displacements, which are interpreted as impulse response functions of a linear dynamic system. Two transport models are discussed: (1) a convective-stochastic approach which takes into account spatial variability of flow and sorption and leads to a lognormal probability distribution of displacements, and (2) the conventional convective-dispersive model with a constant retardation coefficient. To compare their applicability, both models were applied to depth distributions of 90Sr and 137Cs fallout measured in an Orthic Podsol. The convective-stochastic approach was found to provide a better representation of the observed depth distributions. Using this model, migration rates of the radionuclides were calculated.

Models, Theoretical↗