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Biomedical subjects

C Baur

Publications and source records attributed to C Baur.

At least 19 recordsLinked to original sources
PubMed2002

Distribution and unspecific protein binding of the xenoestrogens bisphenol A and daidzein.

Physiological toxicokinetic (PT) models are used to simulate tissue burdens by chemicals in animals and humans. A prerequisite for a PT model is the knowledge of the chemical's distribution among tissues. This depends on the blood flow and also on the free fraction of the substance and its tissue:blood partition coefficients. In the present study we determined partition coefficients in human tissues at 37 degrees C for the two selected xenoestrogens bisphenol A (BA) and daidzein (DA), and their unspecific binding to human serum proteins. Partition coefficients were obtained by incubating blood containing BA or DA with each of the following tissues: brain, liver, kidney, muscle, fat, placenta, mammary gland, and adrenal gland. Blood samples were analysed by HPLC. For BA and DA, all partition coefficients in non-adipose tissues were similar (average values: BA 1.4, DA 1.2). However, the lipophilic properties of both compounds diverge distinctly. Fat:blood partition coefficients were 3.3 (BA) and 0.3 (DA). These values indicate that with the exception of fat both compounds are distributed almost equally among tissues. In dialysis experiments, the unspecific binding of BA and DA with human serum proteins was measured by HPLC. For BA, the total concentration of binding sites and the apparent dissociation constant were calculated as 2000 and 100 nmol/ml, respectively. Because of the limited solubility of DA, only the ratio of the bound to the free DA concentration could be determined and was found to be 7.2. These values indicate that at low concentrations only small percentages of about 5% (BA) and 12% (DA) are as unbound free fractions in plasma. Since only the unbound fraction can bind to the estrogen receptor, binding to serum proteins represents a mechanism that limits the biological response in target tissues.

Animals↗
PubMed2002

HSP70 expression in skeletal muscle of patients with peripheral arterial occlusive disease.

OBJECTIVES: heat shock protein (HSP70) has been studied in the ischaemic myocardium and proven to provide protection against ischaemia. However, HSP70 in ischaemic skeletal muscle in patients with peripheral arterial occlusive disease (PAOD) has not been reported. METHODS: thirty-four patients with PAOD (Fontaine's criteria: stage II: 15; III: 9 and IV: 10, respectively) and ten non-PAOD controls were enrolled in the study. Calf muscle samples were taken. HSP70 was quantitated by SDS-PAGE using ultrasensitive silver staining with reference to a series of standard HSP70, and HSP70 mRNA was estimated using RT-PCR. RESULTS: in comparison with the controls [median with range: 24.8 (14.1-35.6) ng in 2.5 microg total protein], HSP70 was increased significantly in PAOD [stage II: 93.1 (62.7-114.3); stage III: 110.1 (89.7-134.5) and stage IV: 77.4 (67.3-101.1)]. Similar results were obtained with HSP70 mRNA. CONCLUSIONS: HSP70 is increased in the ischaemic skeletal muscle in patients with PAOD, and HSP70 expression is different with regard to clinical stages, and the upregulation of HSP70 mRNA implies that the expression of HSP70 seems to be regulated at transcriptional level.

Aged↗
PubMed2000

A physiological toxicokinetic model for exogenous and endogenous ethylene and ethylene oxide in rat, mouse, and human: formation of 2-hydroxyethyl adducts with hemoglobin and DNA.

Ethylene (ET) is a gaseous olefin of considerable industrial importance. It is also ubiquitous in the environment and is produced in plants, mammals, and humans. Uptake of exogenous ET occurs via inhalation. ET is biotransformed to ethylene oxide (EO), which is also an important volatile industrial chemical. This epoxide forms hydroxyethyl adducts with macromolecules such as hemoglobin and DNA and is mutagenic in vivo and in vitro and carcinogenic in experimental animals. It is metabolically eliminated by epoxide hydrolase and glutathione S-transferase and a small fraction is exhaled unchanged. To estimate the body burden of EO in rodents and human resulting from exposures to EO and ET, we developed a physiological toxicokinetic model. It describes uptake of ET and EO following inhalation and intraperitoneal administration, endogenous production of ET, enzyme-mediated oxidation of ET to EO, bioavailability of EO, EO metabolism, and formation of 2-hydroxyethyl adducts of hemoglobin and DNA. The model includes compartments representing arterial, venous, and pulmonary blood, liver, muscle, fat, and richly perfused tissues. Partition coefficients and metabolic parameters were derived from experimental data or published values. Model simulations were compared with a series of data collected in rodents or humans. The model describes well the uptake, elimination, and endogenous production of ET in all three species. Simulations of EO concentrations in blood and exhaled air of rodents and humans exposed to EO or ET were in good agreement with measured data. Using published rate constants for the formation of 2-hydroxyethyl adducts with hemoglobin and DNA, adduct levels were predicted and compared with values reported. In humans, predicted hemoglobin adducts resulting from exposure to EO or ET are in agreement with measured values. In rodents, simulated and measured DNA adduct levels agreed generally well, but hemoglobin adducts were underpredicted by a factor of 2 to 3. Obviously, there are inconsistencies between measured DNA and hemoglobin adduct levels.

Animals↗
PubMed2000

Human skeletal muscle HSP70 response to physical training depends on exercise intensity.

We have previously reported that HSP70 in human skeletal muscle could be induced by training. However, whether HSP70 induction is dependent upon exercise volume or exercise intensity remains unknown. The aim of the present study was to investigate the relationship between HSP70 and training intensity in rowers. Fourteen well-trained male rowers were divided into two groups (group A, n = 6; group B, n = 8). Group A performed higher intensity exercise during 1st phase, whereas group B performed higher intensity exercise during 2nd training phase. Training volume in 2nd phase increased in both groups. Both training intensity and volume were reduced in 3rd phase. Muscle samples were taken from m. vastus lateralis by fine needle biopsy before training, at the end of the 1st, 2nd and 3rd training phases. HSP70 was quantitatively determined using SDS-PAGE with silver stain. In group A, HSP70 increased significantly from 38 +/- 12 etag before training to 59 +/- 16 etag at the end of the lst training phase (loaded total protein 2.5microg), and decreased afterwards. In group B, HSP70 increase (from 36 +/- 11 etag to 50 +/- 13 etag) in the 1st phase was significantly smaller, there was a further increase of HSP70 in the 2nd phase (60 +/- 14 etag). At the end of the training, HSP70 decreased in both groups. Thus, HSP70 response to training seems to be dependent upon exercise intensity.

Adolescent↗
PubMed2000

Limiting factors on the transformative powers of e-mail in patient-physician relationships: a critical analysis.

In this article I analyze doctor-patient use of e-mail within the context of the evolving doctor-patient relationship and ongoing changes in the U.S. health care system. Evidence from the published literature on doctor-patient relationships and doctor-patient communication, empirical studies of uses of the Internet by doctors and patients, and commentaries about the Internet's role in health care are examined and discussed to reveal common, unsupported assumptions about the likely impact of e-mail on the doctor-patient relationship and also the value structure associated with current e-mail practices between doctors and patients. I argue that existing research does not adequately account for the technical, professional, and economic forces that are shaping doctor-patient use of e-mail. I conclude that physicians' preferences for technical, instrumental exchanges with patients will likely mitigate the positive influence that e-mail could have on the doctor-patient relationship, and doctor-patient communication is unlikely to improve as a result of their use of e-mail.

Communication↗
PubMed1999

Malignant hyperthermia causing Gly2435Arg mutation of the ryanodine receptor facilitates ryanodine-induced calcium release in myotubes.

We have investigated if cultivated muscle cells from malignant hyperthermia (MH) patients can be distinguished pharmacologically from controls. Muscle specimens from four individuals carrying the Gly2435Arg mutation of the skeletal muscle ryanodine receptor protein (RYR1) and from four controls were used to culture myotubes. Resting intracellular calcium concentration ([Ca2+]i) of MH myotubes was similar to controls. However, when ryanodine 0.5 mumol litre-1 was added, the kinetics of the increase in the calcium signals in MH and control cells were significantly different; the time for half maximum increase was mean 197 (SD 131) s for MH cells and 474 (61) s for controls (n = 80 cells each). On average, the area under the MH response curves was twice the control value. These results give rise to hopes that the phenotype of MH can be characterized using cultured human muscle and that a culture-based test for MH susceptibility may eventually be developed.

Adolescent↗
PubMed1999

Screening of the ryanodine receptor gene in 105 malignant hyperthermia families: novel mutations and concordance with the in vitro contracture test.

Malignant hyperthermia (MH) in man is an autosomal dominant disorder of skeletal muscle Ca(2+)-regulation. During anesthesia in predisposed individuals, it is triggered by volatile anesthetics and depolarizing muscle relaxants. In >50% of the families, MH susceptibility is linked to the gene encoding the skeletal muscle ryanodine receptor (RYR1), the calcium release channel of the sarcoplasmic reticulum, on chromosome 19q12-13.2. To date, 21 RYR1 mutations have been identified in a number of pedigrees. Four of them are also associated with central core disease (CCD), a congenital myopathy. Screening for these 21 mutations in 105 MH families including 10 CCD families phenotyped by the in vitro contracture test (IVCT) according to the European protocol revealed the following approximate distribution: 9% Arg-614-Cys, 1% Arg-614-Leu, 1% Arg-2163-Cys, 1% Val-2168-Met, 3% Thr-2206-Met and 7% Gly-2434-Arg. In one CCD family, the disease was caused by a recently reported MH mutation, Arg-2454-His. Two novel mutations, Thr-2206-Arg and Arg-2454-Cys were detected, each in a single pedigree. In the 109 individuals of the 25 families with RYR1 mutations cosegregation between genetic result and IVCT was almost perfect, only three genotypes were discordant with the IVCT phenotypes, suggesting a true sensitivity of 98.5% and a specificity of minimally 81.8% for this test. Screening of the transmembraneous region of RYR1 did not yield a new mutation confirming the cytosolic portion of the protein to be of main functional importance for disease pathogenesis.

Adult↗
PubMed1999

Xenon does not trigger malignant hyperthermia in susceptible swine.

BACKGROUND: Xenon is a noble gas with anesthetic properties currently under investigation for use in humans. This study was performed to evaluate whether xenon may trigger malignant hyperthermia in susceptible swine. METHODS: Nine malignant hyperthermia-sensitive swine (Pietrain) were initially anesthetized with pentobarbital and then ventilated with 70% xenon in oxygen for 2 h. Heart rate, mean arterial pressure, cardiac output, body temperature, arterial and mixed-venous blood gases, and plasma catecholamine and lactate levels were measured every 10 min both during xenon-oxygen ventilation and after a 30-min xenon washout phase followed by subsequent administration of halothane (1% inspired) and succinylcholine (3 mg/kg intravenous). During the investigation, no malignant hyperthermia-specific therapy was instituted. RESULTS: Xenon exposure did not induce any changes in metabolic and hemodynamic parameters nor elevations of the plasma catecholamine levels indicative for an episode of malignant hyperthermia. By contrast, in all animals, within 20 min after the administration of halothane and succinylcholine, fulminant and fatal malignant hyperthermia episodes were initiated. CONCLUSIONS: The authors conclude that xenon does not trigger malignant hyperthermia in susceptible swine.

Amino Acid Substitution↗
PubMed1998

[A remote access system for inquiry of centrally stored data on patients suspected of malignant hyperthermia . A prototypical development for the Internet].

OBJECTIVES: Malignant hyperthermia (MH) is an inherited, potentially life-threatening syndrome of the skeletal muscles. It is a life-threatening complication of anaesthesia with a high mortality (8-10%). The risk of the patient during anaesthesia due to an overlooked predisposition for MH can be reduced by organisational measures, such as, all data of MH-susceptible patients and their families known in Germany must be brought together in a central register, MH-relevant data of patients must be readily retrievable, optional oral advice for those making an inquiry must be available. METHODS: To achieve this goal, a client-server system has been implemented: Standard Multimedia personal computers installed at the user's (anaesthetist's) site, linked to the Internet, will act as clients. On a server, relevant data of patients concerning MH-susceptibility are integrated in a central database. The newly developed software of this project ensures the legally prescribed data security on the server and the data routes. At the client's site, standard software together with automatically installed programmes from the server using Java applets ensure easy use and maintenance. IMPLEMENTATION: The total system was implemented and tested. Its functionality and high availability was demonstrated during this test period. Relevant aspects of data security were successfully examined by the data security officer of the University Hospitals of Baden-Württemberg. The user can optionally call a multifunctional teleconference which secures on-line advice if needed. This system demonstrates a safe and quick retrieval of MH relevant data of patients via Internet while at the same time guaranteeing all aspects of data protection and security. CONCLUSION: A prototypical database access system is described. It ensures safe access to patient data via Internet, while guaranteeing all aspects of data security.

Computer Communication Networks↗
PubMed1998

[Regional distribution of predisposition to maligant hyperthermia in Germany: tate in 1997].

Malignant hyperthermia (MH) is a rare autosomally dominantly hereditary and potentially life-threatening disease. The prevalence of the genetic MH predisposition is estimated as 1:10,000 to 1:20,000. In Germany no data on the regional distribution are available. Therefore, the purpose of this investigation is to summarise and present the epidemiological data of all German MH laboratories. Nine German hospitals offer the specific in vitro contracture test to diagnose the MH predisposition. All German MH laboratories carry out the examination in accordance with the standardised protocol of the European Malignant Hyperthermia Group. The laboratories were asked to provide the number of all patients investigated, excluding those suffering from other neuromuscular diseases, separated according to diagnostic groups and their places of residence, the number of the identified MH-families as well as the number of the clinically suspected and investigated MH cases with their places of residence. Eight MH laboratories provided the requested data. Until September 1997 a total of 2620 patients were investigated. In 865 patients (34%) MH suspicion was confirmed (diagnosis: MHS). 1494 patients (56%) were released by investigation from MH-suspicion (diagnosis: MHN). In 261 patients (10%) the MH-predisposition remained unsolved (diagnosis: MHE). 580 MH families were identified. Among 2620 patients 757 were clinically suspected MH cases. 35% of these suspected MH cases were classified as MHS, 10% as MHE and 55% as MHN. The documentation of the patients places of residence classified as MHS and MHE into a map of Germany demonstrates an exhaustive distribution with an increased regional prevalence in the areas of the MH laboratories. This concentration in the area of the MH laboratories becomes even more evident, when the places of residence of the MH suspected cases are demonstrated. In conclusion, the distribution of the MH predisposition is uniform and exhaustive in Germany. The presented regional concentration of clinically suspected MH cases among the MH laboratories is mainly interpreted as an expression of effective regional education and information. Considering the overall incidence of the MH predisposition as described above only 15-20% of the MH patients have so far been identified. The MH laboratories have already released about 10,000 patients from the suspicion of MH predisposition. A preliminary prevalence of at least 1:60,000 to 1:80,000 in Germany can be estimated according to the presented data.

Epidemiologic Studies↗
PubMed1998

VIRGY: a virtual reality and force feedback based endoscopic surgery simulator.

This paper describes the VIRGY project at the VRAI Group (Virtual Reality and Active Interface), Swiss Federal Institute of Technology (Lausanne, Switzerland). Since 1994, we have been investigating a variety of virtual-reality based methods for simulating laparoscopic surgery procedures. Our goal is to develop an endoscopic surgical training tool which realistically simulates the interactions between one or more surgical instruments and gastrointestinal organs. To support real-time interaction and manipulation between instruments and organs, we have developed several novel graphic simulation techniques. In particular, we are using live video texturing to achieve dynamic effects such as bleeding or vaporization of fatty tissues. Special texture manipulations allows us to generate pulsing objects while minimizing processor load. Additionally, we have created a new surface deformation algorithm which enables real-time deformations under external constraints. Lastly, we have developed a new 3D object definition which allows us to perform operations such as total or partial object cuttings, as well as to selectively render objects with different levels of detail. To provide realistic physical simulation of the forces and torques on surgical instruments encountered during an operation, we have also designed a new haptic device dedicated to endososcopic surgery constraints. We are using special interpolation and extrapolation techniques to integrate our 25 Hz visual simulation with the 300 Hz feedback required for realistic tactile interaction. The fully VIRGY simulator has been tested by surgeons and the quality of both our visual and haptic simulation has been judged sufficient for training basic surgery gestures.

Algorithms↗
PubMed1997

[Sudden death caused by an arterial hydatid embolism].

HISTORY: A 45-year-old woman from Turkey who had been living in Germany for 6 years, suddenly became short of breath, developed seizures and died within 2 minutes. There was no evidence of previous illness. INVESTIGATIONS: At autopsy a large hydatid and many other hydatids of varying sizes were found inside the left heart. Rupture of one of the hydatid cysts in the left atrium had caused embolism to the arterial system. The cyst walls showed typical laminar cuticular structure. The sediments of the cyst fluid contained scolices of Echinococcus granulosus, but no antibodies were demonstrated by indirect haemagglutination. DIAGNOSIS AND CONCLUSION: This is a rare case of Echinococcus granulosus infection, limited to the heart, which had followed an asymptomatic course until sudden death caused by arterial embolism of the hydatids. Such diagnosis should be considered in case of sudden death of persons from areas in which the disease is endemic.

Animals↗
PubMed1997

Liver of the "visible man".

Endoscopic surgery, also called minimally invasive surgery, is presumed drastically to reduce postoperative morbidity and thus to offer both human and economic benefits. For the surgeon, however, this approach leads to a number of gestural challenges that require extensive training to be mastered. In order to replace experimentation on animals and patients, we developed a simulator for endoscopic surgery. To achieve this goal, a first step was to develop a working prototype, a "standard patient," on which the informatic and microengineering tools could be validated. We used the visible man dataset for this purpose. The external shape of the visible man's liver, his biliary passages, and his extrahepatic portal system turned out to be fully within the standard pattern of normal anatomy. Anatomic variations were observed in the intrahepatic right portal vein, the hepatic veins, and the arterial blood supply to the liver. Thus, the visible man dataset reveals itself to be well suited for the simulation of minimally invasive surgical operation such as endoscopic cholecystectomy.

Adult↗
PubMed1997

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and congeners in infants. A toxicokinetic model of human lifetime body burden by TCDD with special emphasis on its uptake by nutrition.

Contents of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and of 16 further congeners--polychlorinated dibenzodioxins and dibenzofuranes (PCDD/PCDF)--were determined in lipids of adipose tissue and of livers of 3 stillborns and of 17 infants (0.43-44 weeks old) who died from sudden infant death syndrome. International toxic equivalents (I-TEq) calculated for the sum of TCDD together with all of the 16 congeners (1.55-29.63 ng/kg lipids of adipose tissue, n = 20; 2.05-57.73 ng/kg liver lipids, n = 19) were within the range of or lower than the values published for adults. TCDD concentrations in lipids of breast-fed infants were higher (0.38-4.1 ng/kg lipids of adipose tissue, n = 9; 0.49-3.9 ng/kg liver lipids, n = 8) compared to non breast-fed subjects (0.16-0.76 ng/kg lipids of adipose tissue, n = 8; 0.29-0.71 ng/kg liver lipids, n = 7). Neither I-TEq values nor TCDD concentrations exceeded values published for adults. Since even in stillborns PCDD/PCPF were found (I-TEq, 9.70-10.83 ng/kg lipids of adipose tissue, 6.17-8.83 ng/kg liver lipids; TCDD, 1.3-2.1 ng/kg lipids of adipose tissue, 0.76-1.5 ng/kg liver lipids; n = 3), transplacental exposure has to be deduced. All of the findings concerning TCDD concentrations in the organism become intelligible on the basis of a physiological toxicokinetic model which was developed to describe the body burden of TCDD for the entire human lifetime in dependence of TCDD uptake from contaminated nutrition. The model reflects sex and age dependent changes in the following parameters: body weight, volumes of liver, adipose and muscle tissue, food consumption, and excretion of faeces. TCDD is supposed to be taken up orally, to be distributed freely in lipids of the organism and to be eliminated unchanged by excretion in lipids of faeces as well as by metabolism in the liver. The model was used to predict the half-life of elimination of TCDD (4 months in newborns increasing to approximately 5 years in adults) and concentrations of this compound in lipids of adipose tissue, blood, liver and faeces at different ages. Furthermore, the influence of breast-feeding on the TCDD burden of a mother, her milk and her child was simulated. The model was validated by means of own data gained in adipose tissue and livers of infants and also using a series of values measured by other authors in mother's milk and in tissues and faeces of infants and adults. Predictions as well as experimental findings demonstrate a distinct increase in the TCDD body burden of breast-fed infants. Generally, it can be concluded for the excretion of unchanged, non-volatile, non protein bound highly lipophilic compounds that their half-life is short in infants (approximately 5 months) and increases to approximately 10 years reached between 40 and 60 years of age.

Adipose Tissue↗
PubMed1996

A physiological toxicokinetic model for 1,3-butadiene in rodents and man: blood concentrations of 1,3-butadiene, its metabolically formed epoxides, and of haemoglobin adducts--relevance of glutathione depletion.

A physiological toxicokinetic (PT) model is presented describing disposition and metabolism of 1,3-butadiene (BU) and 1,2-epoxy-3-butene (BMO) in rat, mouse and man, and of 1,2:3,4-diepoxybutane (BDI) in mice. It contains formation of BMO and BDI, intrahepatocellular first-pass hydrolysis of BMO, conjugation of BMO with glutathione (GSH) and GSH-turnover in the liver. Tissue:air partition coefficients of BU and BMO were determined experimentally. Haemoglobin (HB) adducts of BMO in rodents following exposure to BU were simulated and compared with published data. The model is compared with those published earlier. An attempt was made to compare the carcinogenic potential of BU in mice and rats with respect to the carcinogenic potentials of both epoxides.

Animals↗
PubMed1996

Force feedback for virtual reality based minimally invasive surgery simulator.

This paper presents ongoing research towards an endoscopic surgery simulation system. Our specific application of interest is laparoscopic surgery. The goal is to conceive an endoscopic surgical training tool which allows to realistically simulate the interactions between one or several surgical instruments and the gastrointestinal organs in a virtual reality based environment. An artificial patient is being developed into which endoscopic surgical instruments can be inserted to operate upon virtual organs displayed on a video monitor. In order to achieve a faithful and precise simulation, not only a realistic graphical representation of the organic tissue and its behavior is needed, but also the forces and moments on the surgical instruments encountered during an operation are required to be simulated. The laparoscopic surgery simulator must therefore provide force feedback through the endoscopic instruments manipulated by the surgeon. This paper details the mechanical design of the force feedback mechanisms and addresses some of the technical challenges of this project.

Computer Simulation↗
PubMed1995

Transient post-renal obstruction may protect the kidney against nephrotoxic damage--a case report.

In critically ill patients, acute renal failure is mostly multifactorial in origin. In general, the simultaneous presence of several deleterious factors tends to aggravate the renal damage. The present case report describes a patient with multifactorial acute renal failure, in whom one of the factors contributing to the renal failure, i.e. transient unilateral post-renal obstruction, apparently protected the obstructed kidney against damage from other causes.

Acute Kidney Injury↗