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M Burkhardt

Publications and source records attributed to M Burkhardt.

At least 19 recordsLinked to original sources
PubMed2001

Basis for optimization of in vitro exposure apparatus for health hazard evaluations of mobile communications.

The main objective of this paper is to carefully study the fields induced in flasks exposed to RF electromagnetic fields. The study focuses on the widely used 60 mm Petri dishes and rectangular T-75 flasks for the two following cases: 1) cells in homogeneous suspension and 2) cell monolayers. The dependence of the coupling and the homogeneity of the SAR distribution on frequency (0.7 GHz to 2.5 GHz), polarization (E, H and k polarizations) and the amount of medium (1.9 mm to 4.7 mm medium height) is studied. In addition, the effects of the environment, meniscus and field impedance as well as the distortion of the incident field are discussed. Based on these results, advantages and disadvantages of different fundamental designs of apparatus used in the past are compared. These are TEM cells, HF chambers, radial transmission lines (RTL), waveguides and wire patch cells. Furthermore, the major optimization parameters are identified for the development of highly optimized exposure systems, enabling the conduct of high quality experiments.

Biophysical Phenomena↗
PubMed2001

Developing and deploying a patient safety program in a large health care delivery system: you can't fix what you don't know about.

BACKGROUND: The Veterans Administration (VA) identified patient safety as a high-priority issue in 1997 and implemented the Patient Safety Improvement (PSI) initiative throughout its entire health care system. In spring 1998 the External Panel on Patient Safety System Design recommended alternative methods to enhance reporting and thereby improve patient safety. REDESIGNING THE PSI INITIATIVE: The VA began redesigning the PSI initiative in late 1998. The dedicated National Center for Patient Safety (NCPS) was established. Using the panel's recommendations as a jumping-off point, NCPS began to identify known and suspected obstacles to implementation (such as possible punitive consequences and additional workload). NCPS adopted a prioritization scoring method, the Safety Assessment Code (SAC) Matrix, for close calls and adverse events, which requires assessing the event's actual or potential severity and the probability of occurrence. The SAC Matrix specifies actions that must be taken for given scores. Use of the SAC score permits a consistent handling of reports throughout the VA system and a rational selection of cases to be considered. A system for performing a root cause analysis (RCA) was developed to guide caregivers at the frontline. This system includes a computer-aided tool, a flipbook containing a series of six questions, and reporting of the findings back to the reporter. The final step requires that the facility's chief executive officer "concur" or "nonconcur" on each recommended corrective action. The RCA team outlines how the effectiveness of the corrective action will be evaluated to verify that the action has had the intended effect, and it ascertains that there were no unintended negative consequences. IMPLEMENTATION: Based on successful implementation in two pilots, full-scale national rollout to the 173 facilities began in April 2000 and was concluded by the end of August 2000. NCPS supplied 3 days of training for individuals at each facility. The training included didactic components, an introduction to human factors engineering concepts, and small- and large-group simulation exercises. Facility leaders were reminded of the necessity to reinforce the point that assignment to an RCA team was considered an important duty. DISCUSSION: It is essential to design and implement a system that takes into account the concerns of the frontline personnel and is aimed at being a tool for learning and not accountability. The system must have as its primary focus the dissemination of positive actions that reduce or eliminate vulnerabilities that have been identified, not a counting exercise of the number of reports.

Databases, Factual↗
PubMed2000

KT5823 inhibits cGMP-dependent protein kinase activity in vitro but not in intact human platelets and rat mesangial cells.

Many signal transduction pathways are mediated by the second messengers cGMP and cAMP, cGMP- and cAMP-dependent protein kinases (cGK and PKA), phosphodiesterases, and ion channels. To distinguish among the different cGMP effectors, inhibitors of cGK and PKA have been developed including the K-252 compound KT5823 and the isoquinolinesulfonamide H89. KT5823, an in vitro inhibitor of cGK, has also been used in numerous studies with intact cells to implicate or rule out the involvement of this protein kinase in a given cellular response. However, the efficacy and specificity of KT5823 as cGK inhibitor in intact cells or tissues have never been demonstrated. Here, we analyzed the effects of both KT5823 and H89 on cyclic-nucleotide-mediated phosphorylation of vasodilator-stimulated phosphoprotein (VASP) in intact human platelets and rat mesangial cells. These two cell types both express high levels of cGK. KT5823 inhibited purified cGK. However, with both intact human platelets and rat mesangial cells, KT5823 failed to inhibit cGK-mediated serine 157 and serine 239 phosphorylation of VASP induced by nitric oxide, atrial natriuretic peptide, or the membrane-permeant cGMP analog, 8-pCPT-cGMP. KT5823 enhanced 8-pCPT-cGMP-stimulated VASP phosphorylation in platelets and did not inhibit forskolin-stimulated VASP phosphorylation in either platelets or mesangial cells. In contrast H89, an inhibitor of both PKA and cGK, clearly inhibited 8-pCPT-cGMP and forskolin-stimulated VASP phosphorylation in the two cell types. The data indicate that KT5823 inhibits purified cGK but does not affect a cGK-mediated response in the two different cell types expressing cGK I. These observations indicate that data that interpret the effects of KT5823 in intact cells as the major or only criteria supporting the involvement of cGK clearly need to be reconsidered.

Alkaloids↗
PubMed2000

Receptor- and non-receptor-mediated clearance of big-endothelin and endothelin-1: differential effects of acute and chronic ETA receptor blockade.

AIMS: The aims of this study were to define and characterize the different mechanisms and sites of clearance of plasma endothelin-1 (ET-1) and big endothelin-1 (BigET-1) and evaluate possible effects of ETA versus combined ETA and ETB receptor blockade or endothelin converting enzyme (ECE) inhibition. METHODS: Time courses and sites of clearance were evaluated in Wistar-Kyoto rats after bolus injection of radiolabelled peptides into the carotid artery before or after treatment with LU1 35252 (ETA) and bosentan (ETA and ETB) as receptor antagonists or the ECE inhibitor phosphoramidon. RESULTS: The study shows that differential clearance of 125I-ET-1 and 125I-BigET-1 is mediated by distinct tissue-specific, receptor- and non-receptor-mediated mechanisms. Low levels of plasma ET-1 are rapidly cleared, mainly in the pulmonary circulation, through a low-capacity saturable ETB receptor-linked mechanism. In contrast, BigET-1 clearance is markedly slower, confined largely to liver and kidneys, is essentially non-receptor-mediated and is independent of converting enzyme activity. Acute inhibition of both ETA and ETB receptors with bosentan dramatically prolonged 125I-ET-1 plasma half-life and shifted tissue uptake from lung to liver and kidneys. Pulmonary clearance of 125I-ET-1 was decreased by chronic but not acute treatment with the specific ETA receptor antagonist LU135252. In contrast, 125I-Big-ET-1 clearance and tissue uptake were essentially unchanged by all treatments. CONCLUSIONS: Plasma levels and clearance studies on ET-1 and BigET-1 may provide differential information regarding pathological changes in their separate uptake mechanisms. Such data could have diagnostic or prognostic value in pulmonary, hepatic and renal pathophysiology or future therapeutic monitoring of treatment efficacy following administration of selective receptor antagonists.

Administration, Oral↗
PubMed1998

Differences in energy absorption between heads of adults and children in the near field of sources.

This paper was motivated by a recent article in which the levels of electromagnetic energy absorbed in the heads of mobile phone users were compared for children and adults at the frequencies of 835 MHz and 1,900 MHz. Significant differences were found, in particular substantially greater absorption in children's heads at 835 MHz. These findings contradict other studies in which no significant changes had been postulated. The clarification of this issue is crucial to the mobile communications industry since current SAR evaluations as required by the FCC are only performed with phantoms based on the heads of adults. In order to investigate the differences in absorption between adults and children due to their differing anatomies, simulations have been performed using head phantoms based on MRI scans of an adult (voxel size 2 x 2 x 1 mm3) and two children (voxel size 2 x 2 x 1.1 mm3) of the ages of 3 and 7 y. Ten different tissue types were distinguished. The differences in absorption were investigated for the frequencies of 900 MHz and 1,800 MHz using 0.45 lambda dipoles instead of actual mobile phones. These well-defined sources simplified the investigation and facilitated the comparison to previously published data obtained from several numerical and experimental studies on phantoms based on adults. All simulations were performed using a commercial code based on the finite integration technique. The results revealed no significant differences in the absorption of electromagnetic radiation in the near field of sources between adults and children. The same conclusion holds when children are approximated as scaled adults.

Adult↗
PubMed1998

In vivo analysis of hepatic NADH fluorescence. Methodological approach to exclude Ito-cell vitamin A-derived autofluorescence.

Assessment of hepatic surface NADH fluorescence is complicated by questions concerning the relative contribution of Ito cell-associated vitamin A autofluorescence, which cannot be distinguished from each other using ultraviolet epi-illuminated microfluorographs. However, as presented herein, vitamin A autofluorescence can easily be eliminated due to its rapid photobleaching property. In line with in vitro studies on liver perfusion reported by Suematsu and coworkers (1993b), we assessed NADH fluorescence in liver surface regions, which were epi-illuminated for elimination of vitamin A autofluorescence and were allowed to recover for 20 min prior to onset of the experiment. To assess whether this procedure is stringent for accurate estimation of NADH fluorescence, we studied NADH fluorescence in non prebleached surface regions after a 30 sec and 60 sec epi-illumination period. Epi-illumination of these hepatic surface regions for more than 20 sec guaranteed also complete elimination of vitamin A autofluorescence (Vollmar et al., 1996) and further allowed to calculate the subsequent loss of NADH fluorescence due to a potential photobleaching effect after 30 sec and 60 sec of continuous light exposure. Corresponding data of the present study reveal a constant loss of NADH fluorescence of approximately 20% due to its photobleaching property over the time period from 20-60 sec of epi-illumination. Linear regression analysis of the kinetics of NADH fluorescence upon continuous light exposure allowed the calculation of the initial NADH fluorescence, excluding the interference with the Ito cell vitamin A-derived autofluorescence. The concurrency of this mathematically assessed value for the initial (non-bleached) NADH fluorescence within normal hepatic livers with the recovered value of NADH fluorescence allows the conclusion that the procedure for elimination of vitamin A autofluorescence, including ultraviolet epi-illumination with a subsequent NADH recovery period of at least 20 min, is not a prerequisite for the reliable assessment of intraindividual changes of hepatic NADH fluorescence in vivo. Thus, valid assessment of hepatic NADH fluorescence in vivo can be performed by analyzing initial NADH fluorescence bleaching kinetics, and does not necessarily require the 20 min recovery period after bleaching of the Ito cell vitamin A-derived autofluorescence.

Animals↗
PubMed1997

High-resolution microscopic determination of hepatic NADH fluorescence for in vivo monitoring of tissue oxygenation during hemorrhagic shock and resuscitation.

Impaired microvascular oxygen supply reduces oxidative phosphorylation and causes an increase in cellular NADH, which was monitored densitometrically in vivo by high-resolution fluorescence microscopy (330-390/ > 430 nm excitation/emission wavelengths) in rat livers (n = 8) subjected to hemorrhagic shock and resuscitation. At each time point, NADH fluorescence was recorded from 10 different observation fields of the left liver lobe. Withdrawal of a total of 4.5 ml arterial blood for induction of volume-controlled hemorrhagic shock resulted in an increase in NADH fluorescence by approximately 31% from 45.1 +/- 3.9 to 59.2 +/- 4.2 aU, which was associated with a fall of arterial blood pressure from 110 +/- 3 to 51 +/- 8 mmHg, a decrease in hepatic tissue oxygenation (flexible polarographic surface electrode) from 18 +/- 2 to 2 +/- 1 mmHg, and a restriction of hepatic bile flow from 1.7 +/- 0.1 to 0.5 +/- 0.2 microliter/min x g. Normovolemic resuscitation with 10% hydroxyethylstarch failed to completely restore the metabolic state of liver tissue (NADH fluorescence 49.9 +/- 3.1 aU), arterial blood pressure (83 +/- 8 mmHg), hepatic tissue oxygenation (7.4 +/- 1.5 mmHg), and hepatocellular excretory function (1.3 +/- 0.1 microliters/min x g). During both shock and resuscitation, the ratio between pericentral and periportal NADH fluorescence intensities slightly increased, but calculation of coefficients of variance of interlobular NADH fluorescence did not reveal an increase in heterogeneity of tissue metabolic state. Significant correlations were found between NADH fluorescence and both hepatic tissue oxygenation (r2 = 0.78, P < 0.01) and hepatic bile flow (r2 = 0.85, P < 0.01), indicating that high-resolution intravital microscopic assessment of NADH fluorescence reflects appropriately the relation between local oxygen supply and demand in hepatic tissue in vivo.

Animals↗
PubMed1997

Exposure setup to test effects of wireless communications systems on the CNS.

This paper presents an exposure setup designed for in vivo studies of possible effects on the central nervous system due to the electromagnetic exposure from handheld mobile communications equipment. The setup consists of a carousel on which 10 rats, each restrained in a radially positioned tube, are exposed to the electromagnetic field emanating from a dipole antenna at the center. The rats are positioned with their snouts at a distance of 35 mm from the dipole antenna. The tubes restrain the movement of the animals to such an extent as to allow for well defined exposure conditions, yet without totally immobilizing them. Numerical and experimental dosimetric analysis of the setup was conducted using rats weighing 250-300 g at a frequency of 900 MHz. A detailed rat phantom derived from MRI scans was developed for the numerical assessment with a commercially available code based on the finite integration technique. The results were validated by measurements of the temperature rise in selected points of a rat cadaver. The dosimetric analysis shows that the setup is eminently suitable for central nervous system studies. It enables well defined field strengths to be induced in the brain tissue, whereby the variations in the specific absorption rate averaged over the brain tissue caused by movement and varying animal sizes was shown to be less than +/-16%. The specific absorption rate distribution in the brain is nonhomogeneous but comparable to that induced in the brain of a human using a handheld wireless phone. The efficiency of the exposure is about 0.20+/-0.05 mW g(-1) for the brain average value per 100 mA feedpoint current. The whole-body average specific absorption rate is considerably lower, i.e., about half of that of the brain averaged value. In addition, the setup has been proven to be practical in use, and the stress levels caused by restraining the animals in this setup are deemed by neurologists and veterinary scientists to be very low.

Animals↗
PubMed1996

Single-chain MHC class II molecules induce T cell activation and apoptosis.

MHC class II/peptide complexes displayed on the surface of APCs play a pivotal role in initiating specific T cell responses. Evidence is presented here that components of this heterotrimeric complex can be genetically linked into a single polypeptide chain. Soluble single-chain (sc) murine class II IA(d) molecules with and without covalently attached peptides were produced in a recombinant baculovirus-insect cell expression system. Correct conformation of these molecules was verified based on 1) reactivity to Abs directed against conformational epitopes in IA(d) and 2) peptide-specific recognition of the IA(d)/peptide complexes by T cells. Both sc class II molecules loaded the appropriate peptides and sc class II/peptide fusions were effective in stimulating T cell responses, including cytokine release and apoptosis. Mammalian cells were also found to be capable of expressing functional sc class II molecules on their cell surfaces. The findings reported here open up the possibility of producing large amounts of stable sc class II/peptide fusion molecules for structural characterization and immunotherapeutic applications.

Amino Acid Sequence↗
PubMed1996

Numerical and experimental dosimetry of Petri dish exposure setups.

Crawford TEM cells are often used to expose cell cultures or small animals in order to study the effects caused by high-frequency fields. They are self-contained, easy-to-use setups that provide a rather homogeneous field distribution in a large area around its center, corresponding approximately to far-field conditions. However, a number of conditions must be met if such TEM cells are intended to be used for in vitro experiments. For instance, poor interaction with the incident field must be maintained to avoid significant field disturbances in the TEM cell. This is best achieved with E-polarization, i.e., when the E-field vector is normal to the investigated cell layer lining the bottom of a synthetic Petri dish. In addition, E-polarization provides the most homogeneous field distribution of all polarizations within the entire layer of cells. In this paper, we present a detailed dosimetric assessment for 60 and 100 mm Petri dishes as well as for a 48-well titer plate at 835 MHz. The dosimetry was performed by using numerical computations. The modeling and the simplifications are validated by a second numerical technique and by experimental measurements. For thin liquid layers, an approximation formula is provided with which the induced field strength for many other experiments conducted in Petri dishes can be assessed reliably.

Absorption↗
PubMed1990

5-hydroxytryptamine1A agonists. A new therapeutic principle for stroke treatment.

We conducted the present study to investigate the effects of 5-hydroxytryptamine agonists on brain morphology after the induction of focal cerebral ischemia by permanent occlusion of the left middle cerebral artery in rats and mice. Forty-eight hours after vessel occlusion, the damage was quantified in rats by planimetry and subsequent integration on cresyl violet-stained serial sections and in mice by planimetric analysis of the damaged cortical surface after counterstaining with carbon black. All 5-HT1A agonists investigated substantially decreased cortical infarct size in the rat focal ischemia model (p less than 0.05). Drugs were applied 30 minutes before the induction of ischemia, and efficacy was demonstrated for 8-OH-DPAT (1 mg/kg s.c.), buspirone (10 mg/kg i.p.), gepirone (10 mg/kg i.p.), ipsapirone (10 or 30 mg/kg i.p.), and Bay R 1531 (1 mg/kg i.p.). The most pronounced effects were seen with the higher dose of ipsapirone and Bay R 1531, both compounds reducing cortical infarct size by more than 60%. Except for 8-OH-DPAT, the 5-HT1A agonists also caused a reduction in total infarct volumes. In a separate series, ipsapirone (30 mg/kg i.p.), applied 1 hour after vessel occlusion, led to a reduction in cortical and total infarct volumes by about 50% compared with corresponding controls (p less than 0.05). In neither series was striatal damage influenced. We tested the compounds in the mouse ischemia model over a broad dose range.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1976

The haemolytic effect of phallolysin.

Phallolysin from the toadstool, Amanita phalloides, is a basic protein that causes direct haemolysis of red cells. The dose-response curve is steep; the pH optimum is in the weakly acid range. The rate of haemolysis increases with the concentration of the lysin, the optimal temperature is 20 degrees C. The percentage haemolysis-time curves are S-shaped. Haemolysis is of the non-osmotic type. Ca2+ is not required but inhibits haemolysis in a concentration-dependent fashion, as do Mg2+ and Zn2+. The red cell sensitivity of various animal species decreases in the following sequence:mouse greater than rabbit = guniea pig greater than rat greater than man greater than dog approximately or equal to pig greater than sheep = cattle. Red cells of cattle and sheep are largely resistant. Phallolysin is virtually not consumed on haemalysis: the amount of haemoglobin released increases with the number of red cells applied; on repeated addition of fresh red cells the haemolysate retains its full activity. Phallolysin is not inhibited by serum, albumin, cholesterol, lecithin, cephalin or sphingomyelin; inhibition by red cell ghosts of phallolysin haemolysis is considerably less than that of digitonin haemolysis. At sublytic concentrations phallolysin, unlike benzalkonium chloride, liberates practically no membrane lipids from human red cells. Surface activity of phallolysin does not exceed that of bovine serum albumin.-A saponin-like interaction with cholesterol as the basic mechanism of haemolysis can be disregarded. There is also no evidence suggesting a detergent-like effect.

Amanitins↗