[Study protocol of the VISEP study. Response of the SepNet study group]. / Studienprotokoll der VISEP-Studie. Entgegnung der SepNet-Studiengruppe.

In the commentary by Zander et al. the authors appear concerned about the methods and results of our, at that time, unpublished sepsis trial evaluating hydroxyethyl starch (HES) and insulin therapy. Unfortunately, the authors' concerns are based on false assumptions about the design, conduct and modes of action of the compounds under investigation. For instance, in our study the HES solution was not used for maintenance of daily fluid requirements, so that the assumption of the authors that this colloid was used "exclusively" is wrong. Moreover, the manufacturer of Hemohes, the HES product we used, gives no cut-off value for creatinine, thus the assumption that this cut-off value was "doubled" in our study is also incorrect. Other claims by the authors such as that lactated solutions cause elevated lactate levels, iatrogenic hyperglycemia and increase O(2) consumption are unfounded. There is no randomized controlled trial supporting such a claim - this claim is neither consistent with our study data nor with any credible published sepsis guidelines or with routine practice worldwide. We fully support open scientific debate. Our study methods and results have now been published after a strict peer-reviewing process and this data is now open to critical and constructive reviewing. However, in our opinion this premature action based on wrong assumptions and containing comments by representatives of pharmaceutical companies does not contribute to a serious, unbiased scientific discourse.

[Malignant hyperthermia. The ugly]. / Maligne Hyperthermie. The ugly.

The term "malignant hyperthermia" (MH), regarded as the typical anaesthetic disease, refers to a clinical syndrome of varying intensity (from abortive courses to fulminant crises) and develops only under exposure of certain triggering substances or mechanisms. MH is caused by a defect in the ryanodine receptor subtype 1, which can often be proved genetically. Furthermore, it may also be generated by other mechanisms which disturb the membranous integrity of skeletal muscle cells (e.g. some myotonias, muscular dystrophies, malformation syndromes). Hyperthermia is only one of a number of life-threatening symptoms that may occur during a fulminant crisis, which ultimately results from an excessive release of calcium into the cytoplasm of muscle cells. Due to a current good knowledge about classical triggers, symptoms and therapeutic interventions, a clinical MH presentation may successfully be treated in the perioperative period. However, it appears to be likely that there are unreported cases outside hospitals since atypical courses or alternative MH triggers (e.g. alcohol, drugs, physical stress) may impair the correct diagnosis. In contrast severe hyperthermia can also arise from other drug-induced diseases, e.g. the neuroleptic malignant syndrome or the serotonin syndrome.

[Tumescent anaesthesia for dermatological surgery. Plasma concentrations of lidocaine and prilocaine]. / Tumeszenzlokalanästhesie bei dermatologischen Eingriffen. Plasmakonzentrationen von Lidocain und Prilocain.

BACKGROUND: Tumescent anaesthesia is currently used for several dermatological procedures. The objective of this study was to determine the plasma concentrations of local anaesthetics under real operating conditions with this anaesthetic technique. METHODS: A total of 31 patients received 3 different anaesthetic solutions with prilocaine and lidocaine for several surgical procedures. The concentrations of local anaesthetics, methemoglobin, epinephrine as well as the occurrence of adverse reactions were determined 30 min, 1 h, 3 h, 6 h, 12 h and 24 h after administration RESULTS: Maximum plasma concentrations of prilocaine were measured predominantly after 3 and 6 h, for lidocaine after 6 h. In two patients maximum plasma levels occurred 24 h after infiltration. Although toxic concentrations were not exceeded, side-effects could be observed in four patients. CONCLUSIONS: Even if the measured concentrations of local anaesthetics appeared to be safe, slight and moderate side-effects could be observed in 12.9% of cases. Maximum plasma levels of local anaesthetics may still occur 24 h after administration.

[Streptococcal Toxic Shock-like Syndrome associated with detectable autoantibodies]. / Toxisches Streptokokken Schock Syndrom in Verbindung mit serologisch nachgewiesenen Autoantikörpern.

We report on the severe course of a Streptococcal Toxic Shocklike Syndrome (STSLS). The initial diagnosis as well as the causal therapeutic approaches were complicated and prolongated definitely by the serological detection of auto-antibodies. Besides the presentation of clinical and paraclinical findings the report responds to relevant differential diagnoses and the corresponding strategies of therapeutic intervention.

[Propofol for paediatric patients in ear, nose and throat surgery. Practicability, quality and cost-effectiveness of different anaesthesia procedures for adenoidectomy in infants]. / Propofoleinsatz für Hals-Nasen-Ohren-Eingriffe im Kindesalter. Praktikabilität, Qualität und Kosteneffektivität verschiedener Narkoseverfahren zur Adenotomie bei Kindern.

BACKGROUND: The aim of this study was an improvement in patient comfort, reduction of anaesthesia costs and room contamination by the use of propofol for adenoidectomy. METHODS: A total of 103 infants (aged 1-5 years) undergoing elective adenoidectomy were randomized for anaesthesia with sevoflurane-nitrous oxide/oxygen (group 1), sevoflurane-air/alfentanil (group 2), alfentanil-propofol under induction with sevoflurane (group 3) or alfentanil-propofol (group 4). RESULTS: Using propofol, postoperative agitation and emesis were significantly less and the anaesthesia costs as well as the need for analgesics was reduced compared to inhalative anaesthesia. CONCLUSIONS: The use of propofol for preschool children undergoing ear, nose and throat (ENT) surgery seems to be advantageous because of less postoperative agitation, emesis and costs.

[Pain on injection with propofol]. / Injektionsschmerzen nach Propofolgabe.

Injection-induced pain during induction of anaesthesia can result in patient's discomfort. This can prevent the use of propofol-anaesthesia in paediatric patients. Because of the high incidence of pain on injection with propofol numerous interventions have been tested to prevent this pain including the use of different drugs and physical measures as well as the combination of methods. The use of a single intervention is not as effective as the combination of different preventive measures. Thus the additional application of a venous tourniquet improves the pain reducing effect if drugs with peripheral mechanism of action are used for prevention of pain. Injection of lidocaine with a rubber tourniquet before the propofol injection is recommended as best effective method. In any case a propofol-MCT/LCT-Emulsion should be used for propofol-anaesthesia. Additionally a multimodal strategy that is adapted to the daily clinical practice seems to be convenient. That means, for general anaesthesia opioids or ketamine and for sedation a sub-anaesthetic dose of thiopental can be used for effective prevention of pain. If the prevention of nausea and emesis is intended, antiemetics that are appropriate for prevention of injection pain should be given. For paediatric anaesthesia the application of EMLA-cream seems to be suitable, because it alleviates the pain during venous cannulation at the same time. Although a painfree propofol injection is not possible with every prevention strategy there exist a wide range of effective interventions to prevent pain on injection with propofol. This article reviews methods that have been investigated and established to minimise the incidence of pain.

Anterior sciatic nerve block--new landmarks and clinical experience.

BACKGROUND: Anterior sciatic nerve blocks can be complicated by several problems. Pain can be caused by bony contacts and, in obese patients, identification of the landmarks is frequently difficult. METHODS: In a first step, 100 normal anterior-posterior pelvic X-rays were analyzed. The landmarks of the classical anterior approach were drawn on these X-rays and assessed for their sufficiency. Then, in a prospective case study, 200 consecutive patients undergoing total knee replacement were investigated. These patients received femoral and sciatic nerve catheters for postoperative pain management. Using modified anatomical landmarks, sciatic nerve catheters were inserted 5 cm distal from the insertion site of the femoral nerve block perpendicularly in the midline of the lower extremity. This midline connected the insertion site of the femoral nerve catheter to the midpoint between the medial and lateral epicondyle. Correct catheter positioning was verified by magnetic resonance imaging (MRI) in six patients. RESULTS: Evaluation of pelvic X-rays showed that puncture following the classical landmarks pointed in 51% at the lesser trochanter, in 5% medial to the lesser trochanter and in 42% directly at the femur. In the latter patients, location of the sciatic nerve would have been difficult or even impossible. Using our modified anterior approach, the sciatic nerve could be blocked in 196 patients (98%). In nine patients (4.5%) blockade of the posterior femoral cutaneous nerve failed. Vascular puncture happened in 10 (5%) and bony contact in 35 patients (17.5%). Median puncturing depth was 9.5 (7.5-14) cm. Correct sciatic nerve catheter positioning was verified in all patients who underwent MRI. CONCLUSION: Our landmarks for locating the sciatic nerve help to avoid bony contacts and thereby reduce pain during puncture. Our method reliably enabled catheter placement.

[Treatment of extreme tumour pain with morphine and s-ketamine A case report of an 11-year old girl]. / Therapie extremer Tumorschmerzen mit Morphin und (S)-Ketamin. Falldarstellung eines 11-jährigen Mädchens.

We are reporting on the case of an 11-year old girl with a malignant tumour. The extreme pain throughout the body could not be treated by conventional methods. By intravenous application of a morphine and s-ketamine mixture we were able to achieve a very effective analgesic result. Apart from the opiate effect of the morphine the decisive factor was the NMDA-antagonism of the s-ketamine. The latter suppresses central sensitisation and chronic pain and reduces or even prevents the development of opioid tolerance. It was possible to use smaller opiate doses more effectively, thus reducing the side effects of the pain therapy. Under associated whole-body thermochemotherapy the girl experienced general pain relief and we were able to return to conventional therapy with a fentanyl plaster.

[Catecholamine levels in plasma and cerebrospinal fluid of neurosurgical patients with normal and elevated intracranial pressure]. / Plasma- und Liquor-Katecholamin-Konzentrationen neurochirurgischer Patienten mit normalem und erhöhtem Hirndruck.

OBJECTIVE: Catecholamine levels in the plasma and cerebrospinal fluid of 21 neurosurgical patients with hydrocephalus and with normal and elevated intracranial pressure were determined prospectively in a clinical study. METHODS: The study comprised 11 patients with normal intracranial pressure (8 female, 3 male, group 1) and 10 patients with elevated intracranial pressure (6 female, 4 male, group 2). The patients underwent a ventriculo-peritoneal shunt operation, external ventricular drainage or ventriculocisternostomy. The measuring times were set as follows: time 1: pre-operative; time 2: intra-operative; time 3: post-operative. The anaesthetic for the operations was administered as a total intravenous anaesthesia with propofol and alfentanil, muscle relaxation being achieved with rocuronium bromide or cis-atracurium. RESULTS: Measurements of the catecholamine levels (adrenaline, noradrenaline and dopamine) at the three set times revealed an intra-operative fall compared to the initial pre-operative value and a rise in the catecholamine level again after the operation. It is likely that this largely reflects the course of the anaesthetic. The fall in the plasma catecholamine level was much slighter in group with elevated intracranial pressure. But in the group of patients with elevated intracranial pressure the catecholamine levels found in the plasma were much higher than those of the patients without elevated pressure. In the case of adrenaline, it was possible to demonstrate a statistically significant difference at the three measuring times. This suggests that especially the analyzed adrenaline level in the plasma could take on the role of a marker in cases of elevated intracranial pressure. In group 2, with elevated intracranial pressure, the catecholamine levels in the cerebrospinal fluid (CSF) were considerably higher than those in group 1, but the difference did not reach the significance level. The lack of correlation between the catecholamine values in the plasma and CSF described in the literature (comparison of the corresponding values at time 2) was confirmed for noradrenaline and dopamine in patients with elevated intracranial pressure (group 2). In both groups of patients there was a CSF plasma gradient for dopamine at time 2, i. e. the dopamine level was higher in cerebrospinal fluid than in the plasma. CONCLUSION: The study shows that even a slight rise in intracranial pressure without clinically detectable ischaemia may result in elevated plasma and CSF catecholamine levels. Although catecholamine values are not routine parameters, they can be used in developing procedures to protect the brain in neurosurgical patients.

Sequential effects of propofol on functional brain activation induced by auditory language processing: an event-related functional magnetic resonance imaging study.

BACKGROUND: We have investigated the effect of propofol on language processing using event-related functional magnetic resonance imaging (MRI). METHODS: Twelve healthy male volunteers underwent MRI scanning at a magnetic field strength of 3 Tesla while performing an auditory language processing task. Functional images were acquired from the perisylvian cortical regions that are associated with auditory and language processing. The experiment consisted of three blocks: awake state (block 1), induction of anaesthesia with 3 mg kg(-1) propofol (block 2), and maintenance of anaesthesia with 3 mg kg(-1) h(-1) propofol (block 3). During each block normal sentences and pseudo-word sentences were presented in random order. The subjects were instructed to press a button to indicate whether a sentence was made up of pseudo-words or not. All subjects stopped responding during block two. The data collected before and after the subjects stopped responding during this block were analyzed separately. In addition, propofol plasma concentrations were measured and the effect-site concentrations of propofol were calculated. RESULTS: During wakefulness, language processing induced brain activation in a widely distributed temporofrontal network. Immediately after unresponsiveness, activation disappeared in frontal areas but persisted in both temporal lobes (block 2 second half, propofol effect-site concentration: 1.51 microg ml(-1)). No activation differences related to the task were observed during block 3 (propofol effect-site concentration: 4.35 microg ml(-1)). CONCLUSION: Our findings suggest sequential effects of propofol on auditory language processing networks. Brain activation firstly declines in the frontal lobe before it disappears in the temporal lobe.

[Iatrogenic injuries of the trachea]. / Iatrogene Verletzungen der Trachea.

As a basis for quality assurance measures, we analysed over a period of three years all iatrogenic tracheobronchial injuries that had to be repaired operatively at a university hospital. Twelve patients were affected. In most of these cases, the injuries were the result of an intubation during resuscitation attempts prior to or after admission to hospital (6 patients; 4 of them died later). The ruptures of 5 patients were due to complications of a dilational tracheostomy (1 died). In one case the laceration occurred in the course of a reoperation after oesophagectomy (conservative treatment after dehiscence of the tracheal suture). The tracheobronchial ruptures (length: 2 to 8 cm) were located in the pars membranacea and had surgical repair through a thoracotomy on the right side. During the period of this investigation, 43,773 elective intubations were performed. No such serious tracheal injuries were observed. The cause of death in the patients with tracheal injuries was mainly the underlying disease (resuscitation after myocardial infarction; tracheostomy because of pulmonary failure in septic disorders); however, it is likely that the injuries or the surgical intervention played an additional role in the negative outcome of the patients. The conclusion is that this complication rate must be reduced by in-service training and alteration of the procedures.

Calcium release from sarcoplasmic reticulum is facilitated in human myotubes derived from carriers of the ryanodine receptor type 1 mutations Ile2182Phe and Gly2375Ala.

Malignant hyperthermia (MH) is caused by increased calcium release from sarcoplasmic reticulum, triggered by volatile anesthetics or depolarizing muscle relaxants. Numerous mutations associated with MH have been detected in the skeletal muscle type ryanodine receptor gene (RyR1), but so far facilitated calcium release has only been demonstrated for a few of them. This is a prerequisite for confirming the causative role of an RyR1 mutation for MH. Calcium release from sarcoplasmic reticulum induced by 4-chloro-m-cresol (4CmC), caffeine, and halothane was determined in human myotubes by calcium imaging. The RyR1 Ile2182Phe mutation and the RyR1 Gly2375Ala mutation have been identified in individuals susceptible to MH. In myotubes of individuals carrying the RyR1 Ile2182Phe or the RyR1 Gly2375Ala mutation, the EC(50) for caffeine and halothane was reduced; in the Ile2182Phe myotubes, the EC(50) for 4CmC was also reduced, all consistent with facilitated calcium release from the sarcoplasmic reticulum. From these data we conclude that both mutations are pathogenic for MH.

[Experiences in introducing and using a patient data management system (PDMS). in anesthesiology at the Clinic of Anesthesiology and Intensive Care Medicine of the University of Leipzig]. / Erfahrungen bei der Einführung und Nutzung eines Patientendaten-Managementsystems (PDMS) in der Anästhesiologie an der Klinik und Poliklinik für Anästhesiologie und Intensivtherapie des Universitäts-klinikums Leipzig.

In the field of anaesthesia the demands on the quality and quantity of documentation are increasing constantly. Patient Data Management Systems (PDMS) have proved an effective means of handling the volume of data generated. The main reasons for introducing a PDMS vary greatly, nevertheless, it is possible to formulate general requirements such as those of the "Position Paper of the Study Group on Patient Data Management Systems (PDMS) of the University Departments of Anaesthesiology in Bavaria". Although these requirements are very broad, they provide a good basis for comparing different approaches to computer-assisted documentation in anaesthesiology. The stage currently reached at the Department of Anaesthesiology and Intensive Care Medicine (KAI) of the University of Leipzig is analysed in comparison with the position paper. The COPRA system was established at KAI Leipzig eight years ago. It was developed from an existing version for intensive care medicine. It meets the demands made on it when it was introduced and can be enlarged and adjusted to the special needs of anaesthesiology. One particular requirement was that it should be possible to handle computer-assisted documentation and conventional documentation on paper simultaneously. This requirement is met by making the printed forms and those shown on the VDU practically the same in appearance. The anaesthetist is able to recognize "his" record on the screen. This greatly reduces the time required for familiarization and training. If possible, the orientation and updating of the system should be in the hands of an anaesthetist, since this is the only way to ensure that it remains geared primarily to medical needs. Administrative aspects have to be taken into account, but they should not dominate the system. The anaesthetist managing the system should have some basic training in EDP, or at least take a special interest in it. This ensures that minor enlargements can be carried out easily, as soon as required. Proper, expert evaluation of the compiled data requires both a knowledge of medicine and anaesthesiology and an understanding of how information is presented in an EDP system. Enlargements of the system resulting from increasing documentation obligations and quality assurance can be integrated smoothly. In its current form the system is able to depict all parts of the specialist field with the same user interface. By systematically meeting general requirements and taking the special needs of a hospital into account, it has been possible to create a flexible electronic documentation system covering all areas of the anaesthetist's work.

[Is fiber optic hepatovenous oximetry useful in patients undergoing elective partial liver resection?]. / Eignet sich die fiberoptische Lebervenenoxymetrie als zusätzliches Monitoring bei Patienten mit elektiven Leberteilresektionen?

The validity of continuous measurement of hepatic venous oxygen saturation using a fibreoptic technique was investigated and set in correlation with intermittent measurements of saturation in hepatic venous blood in patients undergoing elective partial liver resection (pLR). Eleven patients (4 m/7 f, average age: 62.6 +/- 11.6 years) were included in the study after approval by the Ethics Committee of the University of Leipzig. A fibre-optic heparinized flow-directed pulmonary catheter (5.5-F) was inserted through the right internal jugular vein into the hepatic vein after induction of balanced anaesthesia (isoflurane/alfentanil). The position of the tip of the catheter was verified by fluoroscopic guidance. The oxygen saturation in the hepatic vein measured by the fibre-optic method and by blood-gas analysis (ShvO2) was compared at nine defined measuring points after in-vivo calibration (baseline). The ShvO2 decreased nonsignificantly from 84.4 +/- 10.4% to 77.1 +/- 19.1% during occlusion of the vessels in the liver hilus (Pringle's manoeuvre). The ShvO2 measured by the fibre-optic method and by blood-gas analysis correlated well (r = 0.815, p < 0.001). The limitations of the method result from artefacts based on surgical manipulations in the portal region (compression of hepatic veins, luxation of the liver). These artefacts can be differentiated by analysis of the pressure curves in the hepatic vein. Nevertheless, fibreoptic hepatovenous oxymetry seems to be a feasible method for continuous monitoring of the ShvO2 under intraoperative conditions in patients undergoing partial liver resection. Ischaemic situations of the liver can be detected and treated early. Additional information can be obtained from analyses of parameters in the hepatovenous blood.

[Metoclopramide and dexamethasone in prevention of postoperative nausea and vomiting after inhalational anaesthesia]. / Metoclopramid und Dexamethason zur Prophylaxe von postoperativer Ubelkeit und Erbrechen nach balancierter Anästhesie.

OBJECTIVE: Because of its complex profile of action (binding to dopamine, serotonin and histamine receptors), low rate of adverse effects and low cost as a medicinal preparation, metoclopramide is an interesting substance for the prophylaxis of post-operative nausea and vomiting (PONV). As a single substance its antiemetic effects are slight at the usual dose, so the aim was to test the efficacy of a combination of metoclopramide and dexamethasone for the prevention of PONV on a group of patients with the same operative trauma. METHOD: All patients (n = 204) were recruited prospectively (January-October 2002) and were to undergo a lumbar disc operation. The anaesthetic was administered according to a standard procedure as a balanced anaesthetic with fentanyl and isoflurane in oxygen/air. 60 min before the end of the operation, all patients were given 10 mg of metoclopramide and 8 mg of dexamethasone intravenously. The Würzburg-Oulu-Score served as an instrument for comparison, because no placebo group has been included. 24 hours after the operation, all patients were asked to report on nausea and vomiting, stating the time and the degree of discomfort (quantification by means of an analogue numerical scale from 0-10). The influence of age, height, weight, duration of the anaesthetic, operating position and increased dexamethasone dose was analyzed in addition to the risk factors according to the score. The cost analysis was based on the purchase prices of the hospital dispensary. RESULTS: The expected PONV incidence was 35.8%; 10% nausea (average intensity 4.3) and 3% emesis (4.8) was reported for the 24-hour period. The rescue medication (dimenhydrinate) was requested 8 times. Nausea was mainly during the early part of the period (0-6 hours). Of 42 patients with a history of PONV, 71% had no symptoms. The Odds Ratios for female sex (2.9), non-smoker status (2.0) and post-operative opioid administration (1.9) correspond to the data given in the literature; it was not possible to determine the significance of a history of PONV as an independent risk factor. None of the other factors investigated had a significant influence on PONV. For the chosen combination of antiemetic drugs the number-needed-to-treat is 3.9 (95% CI: 3.3-4.7). The direct costs of the PONV prophylaxis are 0.65 euro per patient. CONCLUSIONS: The metoclopramide/dexamethasone combination proved to be effective and inexpensive, on the basis of these findings it is used prophylactically at our hospital if only one PONV risk factor exists.

Recent advances in the diagnosis of malignant hyperthermia susceptibility: how confident can we be of genetic testing?

Malignant hyperthermia (MH) is a condition that manifests in susceptible individuals only on exposure to certain anaesthetic agents. Although genetically heterogeneous, mutations in the RYR1 gene (19q13.1) are associated with the majority of reported MH cases. Guidelines for the genetic diagnosis for MH susceptibility have recently been introduced by the European MH Group (EMHG). These are designed to supplement the muscle biopsy testing procedure, the in vitro contracture test (IVCT), which has been the only means of patient screening for the last 30 years and which remains the method for definitive diagnosis in suspected probands. Discordance observed in some families between IVCT phenotype and susceptibility locus genotype could limit the confidence in genetic diagnosis. We have therefore assessed the prevalence of 15 RYR1 mutations currently used in the genetic diagnosis of MH in a sample of over 500 unrelated European MH susceptible individuals and have recorded the frequency of RYR1 genotype/IVCT phenotype discordance. RYR1 mutations were detected in up to approximately 30% of families investigated. Phenotype/genotype discordance in a single individual was observed in 10 out of 196 mutation-positive families. In five families a mutation-positive/IVCT-negative individual was observed, and in the other five families a mutation-negative/IVCT-positive individual was observed. These data represent the most comprehensive assessment of RYR1 mutation prevalence and genotype/phenotype correlation analysis and highlight the possible limitations of MH screening methods. The implications for genetic diagnosis are discussed.

[Current aspects of the diagnosis of malignant hyperthermia]. / Aktuelle Aspekte der Diagnostik der malignen Hyperthermie.

OBJECTIVES: The aim of this work was to give a survey of experiences and results obtained over a period of 15 years of diagnosis of malignant hyperthermia in the MH centre in Leipzig. The new branch of MH diagnosis, the molecular genetics and its general diagnostic potential will be presented in more detail. METHODS: The in vitro contracture test (IVCT), which has been used in our department since 1986, represents the standard method for determining disposition to MH and in addition, suspected MH events were analysed by the clinical grading scale (CGS). In 1999, the diagnosis of MH in our centre was supplemented by molecular genetic examination of the skeletal ryanodine receptor gene (RYR1). RESULTS: A total of 1,456 muscle tests (IVCT) in patients with a potential MH disposition, provided 376 MH susceptible (MHS), 121 MH equivocal (MHE) and 921 MH negative (MHN) results. Out of these 309 persons had a previous clinical MH event, but for the majority of these persons a real MH disposition could be excluded by the IVCT (197 MHN). In 99 independent MH families, the RYR1 was genetically screened identifying a mutation in 46, whereby 18 different RYR1 point mutations were found of which 4 (Arg401Cys, Ile2182Phe, Gly2375Ala, Ile2453Thr) have not yet been published. CONCLUSIONS: The disposition to MH may be assessed by the IVCT, DNA analysis and with limitations by the clinical phenotype. The IVCT represents a highly specific method, the DNA analysis appears to be very specific. Under defined conditions an alternative use of the methods is possible. However, these methods should not be regarded as in competition but rather their potential should be complementary or used in specific situations in order to avoid non-detection of MH events in affected families.

Increased sensitivity to 4-chloro-m-cresol and caffeine in primary myotubes from malignant hyperthermia susceptible individuals carrying the ryanodine receptor 1 Thr2206Met (C6617T) mutation.

Malignant hyperthermia (MH) is an autosomal-dominant disorder of skeletal muscle, triggered by volatile anaesthetics and depolarizing muscle relaxants. The causative defect lies in the control of Ca(2+) release from the sarcoplasmic reticulum in skeletal muscle. Numerous mutations have been detected in the ryanodine receptor 1 (RyR1) gene, but so far an MH-causative role has only been confirmed for 16 human RyR1 mutations. In this report we show that myotubes derived from individuals carrying the RyR1 Thr2206Met (C6617T) mutation have an abnormal response of the intracellular calcium concentration to 4-chloro-m-cresol and to caffeine. Satellite cells were obtained from muscle biopsies of patients referred for diagnosing MH. The intracellular calcium concentration in response to 4-chloro-m-cresol and to caffeine was investigated by fluorescence calcium imaging. In myotubes the half-maximal activation concentration (EC(50)) for 4-chloro-m-cresol was reduced from 203 micro m (wild type) to 98 micro m (Thr2206Met), and for caffeine from 3.8 mm to 1.8 mm. From the reduction of EC(50) we conclude that the RyR1 Thr2206Met mutation is pathogenic for MH.

[Comparative studies of patient positioning for lumbar intervertebral disk operation]. / Vergleichende Untersuchungen zur Lagerung bei lumbalen Bandscheibenoperationen.

For surgery on lumbar disks by the posterior route, patients are placed either on a Wilson frame or in genupectoral position. The aim of the prospective study was to record and describe the haemodynamic changes resulting from the patients' position. After written informed consent had been received, 80 neurosurgical patients undergoing lumbar disk surgery were randomly divided into two groups; group I--Wilson frame, group II--genupectoral position. In each group, 20 patients received total intravenous anaesthesia (Alfentanil or Remifentanil, Propofol) and 20 balanced anaesthesia with Isoflurane and Alfentanil or Remifentanil. Haemodynamic parameters (mean arterial pressure--MAP and heart rate--HR) were recorded automatically at three measuring times (MT): firstly, after induction of anaesthesia; secondly, before re-direction; thirdly, after re-direction on the Wilson frame or in the genupectoral position. Induction of anaesthesia did not lead to a significant decrease in MAP (MT 1: 92.5 +/- 15.2 mmHg, MT 2: 89 +/- 13.4 mmHg, n = 80). In group I (n = 40), no significant changes were observed in MAP and HR at MT 3 (p = 0.882, p = 0.051). In comparison to group I, the genupectoral position was associated with significant drops in MAP and HR. The genupectoral position caused a significant decrease in MAP (p < 0.001) and HR (p = 0.016) at MT 3. Our data suggest that body weight or body mass index do not necessarily lead to a preference for one of the two possible positions of the patient. Complications resulting from haemodynamic changes were not seen in either group. We recommend the Wilson frame for neurosurgical lumbar disk surgery in cases of cardiovascular or cerebrovascular disorders. The adaptive capacities in the genupectoral position as a result of the modifying distribution of blood volume are limited in these patients. Furthermore, the dose-dependent effects of different anaesthetics on haemodynamic parameters in these prone positions should be explored.

Mutation screening in the ryanodine receptor 1 gene (RYR1) in patients susceptible to malignant hyperthermia who show definite IVCT results: identification of three novel mutations.

BACKGROUND: The ryanodine receptor of the skeletal muscle (RYR1) seems to be of outstanding importance in the pathogenesis of malignant hyperthermia (MH). It has been shown that point mutations in the RYR1 gene are strongly associated with the MH phenotype. A correctly determined phenotype is the basic prerequisite for adequate genetic MH screening. In this study we examined only those MH susceptible patients for the presence of potential RYR1 mutations who showed strong pathological muscle responses in the in vitro contracture test (IVCT). METHODS: A total of 56 MHS index patients who complied with the following IVCT criteria were included in the molecular genetic investigation: Contracture forces > or =4 mN at a caffeine concentration of 2.0 mmol/l and > or =8 mN at a halothane concentration of 0.44 mmol/l. DNA sequences of exons 2, 6, 9, 11, 12, 14, 15, 17, 39, 40, 45, 46, 102 of the RYR1 gene were analysed by the direct sequencing technique. Furthermore, if an MH mutation was identified in an index patient, all relatives were screened for their family specific RYR1 defect. RESULTS: In 39 index patients an RYR1 mutation was detected: Arg163Cys (n = 2), Asp166Asn (n = 1), Gly341Arg (n = 2), Arg401His (n = 2), Arg614Cys (n = 12), Asp2129Glu (n = 1),Vol2168Met (n = 1), Thr2206Met (n = 9), Ala2428Thr (n = 1), Gly2434Arg (n = 2), Arg2435His (n = 1), Arg2452Trp (n = 1), Arg2454His (n = 4). Three new RYR1 mutations were identified. We found a potential MH mutation in a further 130 relatives of the 39 index patients. Thirty-seven individuals were classified as MHS exclusively by molecular genetic techniques and did not have to undergo the IVCT. CONCLUSIONS: The ascertained high rate of successful MH mutation screening (69.64%) is obviously associated with the more clearly defined MHS diagnosis in the IVCT. According to the EMHG guidelines for the molecular genetic detection of MH susceptibility, a positive MH disposition could be determined in numerous persons by a less invasive technique.