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LIST OF TEAM MEMBERS
PROJECTS-ABTRACTS
LIST OF ORIGINAL PUBLICATIONS 1994/95 FINANCIAL SUPPORT 1994/95
List of team members
Head: Daniel Scheidegger (up to Dec. 94), Franz Frei (since Jan. 95);
Senior scientists: Dieter Betzendörfer, Jan Davies, Jürgen Drewe (up to Dec. 94), Gerd Fricker, Robert L.Helmreich, Jörg Huwyler, Thomas Kocher, Hans-Gerhard Schäfer, Daniel Scheidegger, Markus Schneider, Karl Skarvan, Wolfgang Studer, Albert Urwyler,
Collaborators: Armin Aeschbach (up to Jan. 95), Ursula Behrens (80%), Franoise Erne-Brand (80%), Kathrin Censier (80%), Jürgen Drewe, Karl Hampl, Lorenz Gürke (Jan. 95), Heike Gutmann (50% since July 95), Mark Kaufmann, Christoph Kindler, Reinhold Rösslein, Stefan Rufer, Olaf Schellscheidt, Christoph Schori, Manfred Seeberger, Daniel Sigg (since 1.3.95), Paul Martin Sutter (up to Dec. 94), Esther Schmid (20%), Pan Tiecheng (50% up to Jan. 95), Zhou Shuhua (50% up to Jan. 95), Wolfgang Ummenhofer (up to 30.9.95).
Doctoral students/diploma students: Simone Bally (up to Oct. 95), Caterina Clusemann (Diploma work finished 1994), Nicola DeGaris (up to Nov. 94), Claudia Dobler (since Nov. 95), William Hines (June - July 95) Geoffrey Holder (since Jan. 95), Daniela Morf (since Oct. 95), Bryan Sexton (since June 95), Michael Török (Diploma work to be finished 1995).
The main laboratory research projects of the department of anaesthesia, which are listed below, were influenced by a number of circumstances: In June 1995, all the members of the department and many friends, colleagues and coworkers outside the department were shocked by the unexpected death of Hans-Gerhard Schäfer, who was the initiator and main supporter of the TOMS project. Daniel Scheidegger and a number of other researchers will continue the project.
The Swiss National Science Foundation supports the blood brain barrier project since April 1995 for 3 years whereas for the rodent CPR project support will continue for 1996 for 1996/97 after an interruption of one year.
An advisory board consisting of seven advisors with various backgrounds (basic scientists, industry research professionals and academic anaesthetists) took place in November 1995. Decisions made by the department for future research will be heavily influenced by the report and the recommendations given by this board.
Projects-Abstracts
W. Studer, A. Aeschbach, D. Scheidegger, Z. Shuhua, P. Tiecheng
Coronary perfusion pressure remains to be the single most important determinant of return of spontaneous circulation as well as survival in our rodent model of ventricular fibrillation and precordial chest compression.This could be confirmed using the non-adrenergic pressure agents arginine-vasopressine and angiotensin II, revealing similar survival rates as the adrenergic agents epinephrine and methoxamine. Endotheline-1, another potent vasoconstricting peptide,given exogenously,had no effect on the observed variables (coronary perfusion pressure, return of spontaneous circulation, 60 min survival) and failed as a marker of low flow in an other model (hemorrhagic shock).
A. Urwyler, U. Behrens, K. Censier, L. Gürke, M. Kaufmann, C. Kindler, R. Rösslein, S. Rufer, E. Schmid, M. Seeberger, P.M. Sutter, D. Sigg, W. Ummenhofer
Malignant hyperthermia (MH) research focused on two main projects: (1) Genetic research in cooperation with the Department of Biochemistry, University of Cork (Dr. T. McCarthy) and the Institut of Genetics, University of Würzburg (Prof. C. Müller-Reible).(2) Development of a cell culture model for an alternative diagnostic test of MH susceptibility and for human MH research. As of the end of 1995, 16 genetic ryanodine receptor mutations on chromosome 19 have been found which could be responsible for MH susceptibility. However, in the genetic region encoding for the ryanodine receptor only 3 out of 16 mutations (Gly341Arg, Arg614Cys, Gly2433Arg) have been found in about 10% of Swiss MH families. These data support the view that MH is a very heterogentic disease. From nearly all patients presenting for a diagnostic muscle biopsy for the halothane, caffeine and ryanodine contracture tests, we now obtain primary skeletal muscle cell cultures. Because MH susceptible subjects have an abnormal myoplasmic calcium regulation following exposure to volatile anaesthetics, the effects and mechanisms of halothane on intracellular calcium concentration will now be investigated using the calcium fluorescence marker Fura-2 and fluorescence microscopy on single primary muscle cells from MH susceptible and MH negative subjects.
The Official Homepage of the European MH group
Please send questions about the MH research projects to PD Dr. A. Urwyler (urwyler@ubaclu.unibas.ch) or to Dr. D. Sigg (sigg@ubaclu.unibas.ch)
TRANSPORT OF DRUGS ACROSS THE
BLOOD-BRAIN BARRIER
J. Huwyler, J. Drewe, F. Frei, G.Fricker, U. Behrens, H. Gutmann, C. Klusemann, M. Török
In many cases transport of peripherally administered drugs to the brain is severely limited by the low permeability of the blood-brain barrier. A cell culture model of the blood-brain barrier has been developed and validated that is used to study factors influencing transport properties of selected drugs. Our cell culture system consists of primary cultures of porcine brain capillary endothelial cells. This model allows to study uptake kinetics of isotope-labeled drugs by endothelial cells. In addition, transport kinetics and pathways of selected substances across endothelial monolayers can be investigated. One of the substances which is of special interest for us is morphine-6-glucuronide. This drug belongs to the major metabolites of morphine. The potent analgesic action of this compound together with its potential lower apparent toxicity in man, when compared with morphine, showed its clinical importance. Using the above mentioned cell culture system, transport properties of morphine-6-glucuronide were studied. Uptake and transport of morphine-6-glucuronide was marginal and in the range of the extracellular marker sucrose. However, uptake of morphine-6-glucuronide was considerably enhanced in presence of the inhibitors of P-glycoprotein verapamil or vincristine. The finding that morphine-6-glucuronide may serve as a substrate for P-glycoprotein was confirmed in multidrug-resistant P388 tumor cells. Expression of P-glycoprotein in cultured brain capillary endothelial cells was shown by Western blot technique. We conclude that penetration of the blood-brain barrier by morphine-6-glucuronide may depend on the expression of the product of the multidrug-resistance (MDR 1) gene in brain capillary endothelial cells.
NERVUS
VAGUS-MODEL
M. Schneider, F. Erne-Brand, K. Hampl, J. Drewe
Using an in vitro model, we demonstrated that the a2-receptor agonist clonidine produced a reversible concentration-dependent inhibition of nerve conduction in rabbit C-fibers. This local anesthetic activity of clonidine was not counteracted by yohimbine, an a2-receptor antagonist which revealed a similar efficacy in inhibiting neural impulse traffic. Although clonidine depolarized the resting membrane potential, it reduced the activity-induced depolarization thus increasing the hyperpolarizing afterpotentials. This suggests that clonidine might interact with potassium currents generated by inward rectifying potassium channels and/or ionic currents generated by the electrogenic Na+-K+ pump. In order to assess the molecular mechanisms related to the modulation of ionic currents by clonidine, patch-clamp studies are warranted.
TEAM ORIENTED MEDICAL SIMULATION (
TOMS)
H-G. Schäfer, D. Betzendörfer, D. Scheidegger, R.L. Helmreich, Bryan Sexton, J. Davies, Th. Kocher, O. Schellscheidt, C.Schori
1994: TOMS efforts this year were devoted to conceptualization of a model for full operating room simulation, installation of hardware and software for simulation of anaesthesia and surgery using an instrumented mannequin, proving tests of the equipment and procedures, and training of staff. 1995. During this year the facility became operational and three activities were undertaken. First, formal human factors simulation training was begun and sixteen courses for 58 Kantonsspital staff were conducted. Two Notarzt courses were also conducted. These courses included a human factors briefing, a simulated induction and operation including one or more critical events, and a human factors debriefing including use of videotapes of the group's behaviour. Second, formal data collection using quantitatively defined measures of behaviour was initiated for both simulations and scheduled operations in theatre. The data collected provide a baseline for measuring the impact of human factors training and simulation. An interim report on preliminary findings has been completed. Data collection will be an ongoing process. The project is coordinated with the Department's Quality Assurance program. Third, a human factors seminar for senior staff (anaesthesia, surgery, and nursing) was conducted. This course forms the basis for a new human factors seminar for Oberrzte and Schichtleitungen. Development of this course is nearly complete. It will contain sections on general human factors, performance evaluation, effective communication, and strategies for providing feedback to trainees.
link toHuman factors in the OR
List of original publications 1994/95Keating K.E., Quane K.A., Manning B.M., Lehane M., Hartung E., Censier K., Urwyler A., Klausnitzer M., Muller C.R., Heffron J.A., McCarthy T.V.: Detection of a novel RYR1 mutation in four malignant hyperthermia pedigrees. Hum. Mol. Genet. 3: 1855-1858, 1994.
Schfer HG Helmreich RL Scheidegger D. Human factors and safety in the emergency room. Resuscitation 28 :221-225, 1994
Urwyler A, Censier K, Kaufmann MA, Drewe J.: Genetic effects on the variability of the halothane and caffeine muscle contracture tests. Anesthesiology 80: 1287-1295, 1994.
Huwyler J., Rufer S., Ksters E., Drewe J.: Rapid and highly automated determination of morphine and morphine-glucuronides by on-line solid phase extraction and liquid chromatography. J. Chromatogr. B, 674: 57-63, 1995.
Schfer HG, Scheidegger D. The search for quality and the role of human factors in medicine. Earth Space Review 4: 20-23, 1995
Seeberger M.D., Urwyler A.: Paravascular lumbar plexus block: block extension after femoral nerve stimulation and injection of 20 vs. 40 ml mepivacain 10 mg/ml. Acta Anaesthesiol. Scand. 39: 769-773, 1995.
Financial support 1994/95Swiss National Science Foundation (Grant 3200-040429) to H-G Schfer/D. Betzendoerfer. Title: Team oriented medical simulation. Available credit is SFr. 92.000 / 1 year. The credit did start Oct 1994
Swiss National Science Foundation (Grant 32-25604.88) to M. von Planta. Title: Endothelial control of coronary perfusion pressure during rodent cardiopulmonary resuscitation. Available credit is SFr. 150'000 / 2 Years. The credit did start April 1992.
Anästhesieverein.
Industrial support: Spacelabs; Dräger; Olympus, Astra Pharmaceutica AG (Sfr. 10'000.-- per year)
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