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Biomedical subjects

E Hartung

Publications and source records attributed to E Hartung.

At least 19 recordsLinked to original sources
PubMed1998

[Recovery time after (S)-ketamine or ketamine racemate. Recovery time after short anesthesia in volunteers].

UNLABELLED: The anaesthetic potency of the (S)-ketamine isomer is approximately double that of racemic ketamine. The aim of this study was to compare the recovery of cerebral function after a bolus of 1.3 mg/kg racemic ketamine or 0.65 mg/kg (S)-ketamine followed by continuous application of 4 or 2 mg/kg x h over 15 minutes. METHODS: With their informed consent and approval of the local ethics committee 12 healthy volunteers were enrolled in a double-blind, cross-over study. All drugs were dissolved in identical volumes. On three dates with an interval of one week at least ketamine/NaCl, (S)-ketamine/physostigmine or (S)-ketamine/NaCl was administered (table 1). The sequence was randomized. In addition, the unspecific antagonistic potential of the centrally acting, cholinergic agonist physostigmine (0.012 mg/kg) after (S)-ketamine was tested against saline-placebo. Neuropsychological tests (tests 3-5 of the syndrome-short-test [Erzigkeit, see references]) were used to quantify cerebral function before and at 45, 75, 105, 135, 165 and 195 min after anaesthesia. All data are mean values and standard deviation. Comparisons over time and between drugs were carried out using two-dimensional analysis of variance (ANOVA). Wilcoxon-tests were used post-hoc. p < 0.05 was considered significant. RESULTS: After (S)-ketamine the subjects were able to carry out the tasks more rapidly than after racemic ketamine (p < 0.05). Mean time to reach preoperative test performance +10% was 117.5 min for (S)-ketamine/physostigmine, 121.3 min for (S)-ketamine/NaCl and 141.6 min for racemic ketamine (p < 0.05 between (S)-ketamine and racemic ketamine). No differences were found between physostigmine and placebo. The incidence of side effects (mainly nausea, vomiting) was not different. DISCUSSION: (S)-ketamine offers a shorter recovery time after short anaesthesia compared to racemic ketamine. The investigated dose of physostigmine was probably too low to produce antagonism of (S)-ketamine. An increased dosage of physostigmine has yet to be studied, but is likely to cause a higher rate of side effects such as nausea, vomiting, bradycardia and possibly even tonic-clonic seizures.

Adult↗
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

Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation.

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that is triggered in genetically predisposed individuals by common anesthetics and muscle relaxants. The ryanodine receptor (RYR1) is mutated in a number of MH pedigrees, some members of which also have central core disease (CCD), an inherited myopathy closely associated with MH. Mutation screening of 6 kb of the RYR1 gene has identified four adjacent novel mutations, C6487T, G6488A, G6502A, and C6617T, which result in the amino acid alterations Arg2163Cys, Arg2163His, Val2168Met, and Thr2206Met, respectively. Collectively, these mutations account for 11% of MH cases and identify the gene segment 6400-6700 as a mutation hot spot. Correlation analysis of the in vitro contracture-test data available for pedigrees bearing these and other RYR1 mutations showed an exceptionally good correlation between caffeine threshold and tension values, whereas no correlation was observed between halothane threshold and tension values. This finding has important ramifications for assignment of the MH-susceptible phenotype, in genotyping studies, and indicates that assessment of recombinant individuals on the basis of caffeine response is justified, whereas assessment on the basis of halothane response may be problematic. Interestingly, the data suggest a link between the caffeine threshold and tension values and the MH/CCD phenotype.

Female↗
PubMed1998

Multicentre evaluation of ryanodine contracture testing in malignant hyperthermia. The European Malignant Hyperthermia Group.

A common protocol for in vitro contracture testing using the plant alkaloid ryanodine has been used by the European Malignant Hyperthermia Group since 1993. This protocol describes a test using I mumol/litre of high purity ryanodine (98%) added as a single bolus dose. The main aim of this study was to compare the results obtained with this test between laboratories with a view to assessing the validity of adopting common diagnostic end-points for use in future collaborative studies. In order to do this it was first necessary to determine the optimum cut-off values of the end-points for discriminating between patients diagnosed as susceptible or not to malignant hyperthermia. The end-points under evaluation were expressed in terms of time after application of ryanodine at which a certain degree of contracture develops. In this study, four end-points were investigated: time to initial contracture development (Ot); time to development of a 10-mN contracture (10t); time from addition of ryanodine to when baseline tension exceeds pre-drug tension (0tp); and time for contracture to reach 10 mN above pre-drug baseline tension (10tp). This protocol was developed initially and used by three investigating centres and the initial assessment of the end-points and their discriminatory ability was made using the first 100 patients from each of centres 1 and 2, and the first 90 patients from centre No. 3. Optimal cut-off values for each of the end-points were determined using logistic regression analysis. Discriminatory ability was improved by combining the Ot and 10t end-points (P < 0.05) but not significantly by combining the 0tp and 10tp end-points. Both methods of categorization were highly sensitive and specific compared with the current standard diagnostic tests. Results from eight additional diagnostic centres which have used the ryanodine contracture test more recently, while indicating that susceptible and normal individuals can be distinguished within a single laboratory, produced a level of variability between testing centres for the ryanodine contracture test that is incompatible with the use of common cut-off values. Possible causes for this variability between laboratories are discussed.

Evaluation Studies as Topic↗
PubMed1997

In vitro contracture test for diagnosis of malignant hyperthermia following the protocol of the European MH Group: results of testing patients surviving fulminant MH and unrelated low-risk subjects. The European Malignant Hyperthermia Group.

BACKGROUND: Determination of sensitivity and specificity of the in vitro contracture test (IVCT) for malignant hyperthermia (MH) susceptibility using the European MH Group (EMHG) protocol has been performed in some laboratories but only on a small sample from the combined EMHG. Thus, the purpose of the present study was to determine combined EMHG sensitivity and specificity of the test. METHODS: Results of IVCT of patients with previous fulminant MH and normal, low-risk subjects (controls) were collected from 22 centres of the EMHG. IVCT was performed according to the EMHG protocol. Patients were included in the study if the clinical crisis had a score of at least 50 points with the Clinical Grading Scale. Low-risk subjects were included provided they did not belong to a family with known MH susceptibility, they had not developed any signs of MH at previous anaesthetics, and they did not suffer from any neuromuscular disease. For inclusion of both MH patients and low-risk subjects, at least 1 muscle bundle in the IVCT should have twitches of 10 mN (1 g) or more. For evaluation of individual tests, only muscle bundles with twitch heights of 10 mN (1 g) or more were used. RESULTS: A total of 1502 probands had undergone IVCT because of a previous anaesthesia with symptoms and signs suggestive of MH. Of these, 119 had clinical scores of 50 and above. From these 119 MH-suspected patients and from 202 low-risk subjects, IVCT data were collected. Subsequently, 14 MH-suspected patients were excluded from further analysis for the following reasons: In 3 patients, the suspected MH episode could be fully explained by diseases other than MH; in 11 MHS patients, IVCT was incomplete (n = 1), data were lost (n = 3), or none of the muscle bundles fulfilled twitch criteria (n = 7). Of the remaining 105 MH-suspected patients, 89 were MHS, 10 MHEh, 5 MHEc, and one MHN. Thus, we observed a diagnostic sensitivity of the IVCT of 99.0% if the MHE group is considered susceptible (95% confidence interval 94.8-100.0%). Of the 202 low-risk subjects, 3 were MHS, 5 MHEh, 5 MHEc, and 189 MHN. This gives a specificity of the IVCT of 93.6% (95% confidence interval 89.2-96.5%). CONCLUSION: The IVCT for diagnosis of MH susceptibility in Europe has a high sensitivity and a satisfactory specificity.

Adolescent↗
PubMed1996

Malignant hyperthermia (MH) diagnostics: a comparison between the halothane-caffeine- and the ryanodine-contracture-test results in MH susceptible, normal and control muscle.

Recent studies demonstrated different contracture responses in muscle from malignant hyperthermia susceptible (MHS) compared to normal (MHN) individuals following exposure to the plant alkaloid ryanodine in-vitro. To confirm if ryanodine has a specific action in MHS muscle, the effect of a single concentration was investigated in skeletal muscle from MHS, MHN and control subjects using a new evaluation technique. In-vitro contracture test (IVCT) and MH diagnosis were performed according to the European Protocol in 86 patients sent to us for MH diagnostic testing and in 24 controls. Viable fresh muscle bundles were exposed to a single bolus of ryanodine 1.0 microM. Contracture onset time (OTp: defined as the time (min) from administration of ryanodine to the start of a contracture as measured by a contracture exceeding predrug baseline height), and the time to an increase of the baseline height to 10 mN above the predrug level (10Tp) were recorded. 29 patients were identified by IVCT to be MHS, 50 MHN, 7 MHE (equivocal) and 24 controls MHN. The indices from the ryanodine test separated all MHS (OTp: < 16 min; 10Tp < 27.4 min) from MHN (> 18 and > 27.7 min) and control subjects (> 17.4 and > 29 min). Values for MHE (equivocal) individuals ranged from 17.1 to 27.8 min for the OTp and from 32 to 49.2 min for the 10Tp. 5 patients with fulminant MH crises were included in the MHS group and showed the 95% confidence intervals (CI) of the median value < or = 8.05 min (OTp) and < or = 13.35 min (10TP) for MHS. In contrast, CI of the median value for the control group were found to be > or = 25.2 min (OTp) and 43.15 min (10Tp) for normal muscle. Thus the ryanodine test protocol showed markedly different contractures in MHS and MHN or control muscle. These results suggest that MHS muscle has a higher sensitivity to ryanodine. However, the protocol should be investigated for reproducibility and validation of thresholds by other laboratories. Ryanodine can help to improve MH diagnostic tests.

Adolescent↗
PubMed1996

Early cerebral functional outcome after coronary artery bypass surgery using different acid-base management during hypothermic cardiopulmonary bypass.

BACKGROUND: Cerebral injury can render meaningless an otherwise successful cardiac operation. As carbon dioxide management during hypothermic cardiopulmonary bypass has a major impact on cerebral blood flow during bypass, it may also influence postoperative cerebral function. The objective of this prospective, controlled, double-blind study was to compare the effect of pH-stat (temperature correction of blood gas analyses) or alpha-stat (no temperature correction) on brain function. METHODS: Cerebral function was assessed non-invasively using neurological examination, a neuropsychological test battery, quantitative electroencephalogram and the cognitive evoked potential P300 preoperatively and on postoperative day 7 or 8. Forty-five patients undergoing elective aortocoronary bypass grafting in barbiturate/opiate anesthesia were randomised into a pH-stat-(n = 23) and an alpha-stat-group (n = 22). Membrane oxygenators with arterial line filtration and non-pulsatile flow at a perfussion pressure of 50-60 mmHg were used throughout. RESULTS: One patient in each group developed a new paresis. Among 49 comparisons of cerebral function parameters, only 3 showed significant differences at the 5%-level, i.e. exactly what is expected purely by chance. These differences were too small to be clinically relevant and favored either pH-stat (theta-amplitude) or alpha-stat (subtest 3 of syndrome-short-test, number of mistakes in aiming). CONCLUSION: Under the bypass conditions of this study there was no difference in early cerebral functional outcome between pH-or alpha-stat carbon dioxide management during hypothermic cardiopulmonary bypass.

Acid-Base Equilibrium↗
PubMed1995

P300-mapping--a neurophysiological tool to quantify cerebral dysfunction after coronary artery bypass grafting.

Objective parameters are needed to quantify cerebral dysfunction following cardiac surgery in outcome and comparative studies. In this investigation we assessed the value of the late auditory evoked potentials N100 and P300 to measure the neuropsychological deficit after coronary artery bypass grafting (CABG). N100, an exogenous potential is influenced by the stimulus pattern (frequency, intensity and stimulus presentation rate). P300, an endogenous potential, depends on the cognitive processing invoked by the stimulus. With approval of the Human Investigation Committee and the patients' consents, 52 subjects undergoing elective CABG were enrolled. Operation, extracorporal circulation, anesthesia and postoperative intensive care were standardized. Twenty-channel recordings of N100 and P300 were obtained for off-line analysis. P300 was elicited using an oddball paradigm with rare target tones interspersed among frequent non-target tones. Additionally, neuropsychological tests (syndrome short test SKT and letter cancellation test) were carried out. Neurological examination and all tests were compared preoperatively and one week postoperatively. A significant deterioration in cerebral function was documented by the SKT score (P = 0.04), an increase in P300 latency (P = 0.004) and an increase of mistake rate in counting the P300 target tone (P = 0.02). No differences between preoperative and postoperative testing were found for letter cancellation, P300 amplitude and any N100 parameter. No correlation was found between the preoperative/postoperative changes in SKT score and P300 latency. P300 was proved to be an objective neurophysiological parameter that allows for the quantification of cerebral function after CABG.

Aged↗
PubMed1995

The vibrotactile threshold (VT) at the fingertips of chain saw operators.

The vibration sensitivity of the skin at the ten fingertips was tested with 72 chain saw operators examined due to VWF-disease and compared with controls. The vibrotactile perception threshold (frequency f = 125 Hz, load p = 1.3 N) proved to be 3 to 5 times as high for the exposed group compared to controls. There was no correlation between vibration sensitivity and peripheral circulation found in cold provocation test. Two different testing instruments (pallaesthesiometer = vibrotactometer) showed significant differences in results probably due to different technical details of the methods. It may be concluded that a standardization of the instrumentation and method is necessary for testing the vibrotactile perception threshold as a part of the nervous function in a comparable manner.

Adult↗
PubMed1994

[Malignant hyperthermia].

Malignant hyperthermia (MH) is a rare, life-threatening pharmacogenetic disease. The genetic incidence is estimated to be 1:10,000. In predisposed individuals, MH is triggered by volatile anaesthetics and/or depolarizing muscle relaxants by an abnormal increase of intracellular calcium concentration in skeletal muscle cells. The clinical presentation may vary from abortive MH to the fulminant MH crisis. Early diagnosis, the use of electrocardiography and capnography for anaesthetic monitoring, immediate cessation of trigger agents and dantrolene treatment are essential components of an effective MH therapy. In some MH families, a genetic alteration of the ryanodine receptor gene (a calcium channel of the sarcoplasmic reticulum) on chromosome 19 has been identified as the potential cause of MH susceptibility. Recent molecular biological findings support the view of MH being a heterogenetic disease. At present, the diagnosis in potentially MH-susceptible individuals is still made using the in vitro halothane and caffeine muscle contracture test.

Anesthesia↗
PubMed1994

Detection of a novel RYR1 mutation in four malignant hyperthermia pedigrees.

Malignant hyperthermia (MH) is a potentially fatal autosomal dominant disorder of skeletal muscle and is triggered in susceptible people by all commonly used inhalational anaesthetics and depolarizing muscle relaxants. To date, six mutations in the skeletal muscle ryanodine receptor gene (RYR1) have been identified in malignant hyperthermia susceptible (MHS) and central core disease (CCD) cases. Using SSCP analysis, we have screened the RYR1 gene in affected individuals for novel MHS mutations and have identified a G to A transition mutation which results in the replacement of a conserved Gly at position 2433 with an Arg. The Gly2433Arg mutation was present in four of 104 unrelated MHS individuals investigated and was not detected in a normal population sample. This mutation is adjacent to the previously identified Arg2434His mutation reported in a CCD/MH family and indicates that there may be a second region in the RYR1 gene where MHS/CCD mutations cluster.

Amino Acid Sequence↗
PubMed1994

Gasoline vapors induce severe rhabdomyolysis.

A young patient developed rhabdomyolysis after accidentally inhaling gasoline vapors. Although there had been no preexistent myopathy, the caffeine and halothane contracture test classified the patient as being malignant hyperthermia-susceptible (MHS). Abnormal contractures also occurred after exposure of muscle bundles to benzine (at 0.01%); in four control tests, benzine-induced contractures (at 0.1%) could be elicited in MHS, but not in normal, muscles. The complex composition of benzine seems to contain potentially hazardous agents that trigger MH.

Adult↗
PubMed1994

[Ketamine racemate versus S-(+)-ketamine with or without antagonism with physostigmine. A quantitative EEG study on volunteers].

The potency of S-(+)-ketamine is approximately double that of the racemic ketamine. This study was carried out to investigate the recovery of cerebral electrical function after a bolus of 1.3 mg/kg ketamine or 0.65 mg/kg S-(+)-ketamine and subsequent continuous application of 4 mg/kg h ketamine per h or 2 mg/kg S-(+)-ketamine, per h for 15 min. Furthermore, the centrally acting, cholinergic agonist physostigmine has been reported to antagonize ketamine and to shorten the recovery period. Therefore, after S-(+)-ketamine 0.012 mg/kg physostigmine was tested against saline placebo. METHODS. With their own informed consent and the approval of the ethics committee 12 healthy volunteers were enrolled in a double-blind cross-over study. All drugs were dissolved in identical volumes. On three dates with intervals of at least 1 week between, ketamine/NaCl, S-(+)-ketamine/physostigmine or S-(+)-ketamine/NaCl was administered (Table 1). The sequence was randomized. The EEG was recorded from 20 sites according to the 10/20 system and after Fast-Fourier transformation computed into amplitudes within the delta, theta, alpha, and beta bands and within the total spectrum. The median, the spectral edge frequency and the dominant frequency (dF) were also determined. Mean values of all electrodes before and at 10, 15, 30, 45 and 195 min after the bolus injection were compared using two-dimensional analysis of variance (ANOVA, significance level P < 0.05). RESULTS. The characteristic increase in theta-amplitude and decrease of alpha-amplitude were observed after ketamine and S-(+)-ketamine. Median and dF dropped from the alpha to the theta frequency range. Ketamine led to a greater increase in total, delta, theta and beta amplitude during anaesthesia. 3 hours after ketamine/S-(+)-ketamine anaesthesia a significant decrease in the median and dominant frequency and in total, delta, theta, alpha and beta amplitudes confirmed residual impairment of cerebral function after all study drugs. No differences were found between physostigmine and placebo. DISCUSSION. The EEG changes during ketamine/S-(+)-ketamine administration suggest a slightly deeper anaesthetic level after ketamine. The course of recovery was not different after ketamine and after S-(+)-ketamine. The spectral edge frequency did not differ between measurement points, and is therefore not suitable for assessment of the depth of anaesthesia reached with ketamine/S-(+)-ketamine. The dose of physostigmine tested was probably too low to produce antagonism of S-(+)-ketamine. An increased dosage of physostigmine has yet to be studied, but is likely to cause a higher rate of side effects, such as nausea, vomiting and bradycardia, and possibly even tonic-clonic seizures.

Adolescent↗
PubMed1993

Effects of grip and push forces on the acute response of the hand-arm system under vibrating conditions.

The purpose of the occupational medicine component of a joint research project was to study the effects of grip and push forces on the acute reaction of the hand-arm system under vibrating conditions. Several series of experiments were carried out by means of a vibration simulator in a laboratory environment in order to study biodynamic vibration behaviour, muscle response, skin temperature, shifts of the vibration perception threshold and the intensity of subjective vibration perception; in addition, field tests with hammer drills were conducted. On the whole, the findings obtained suggest that the coupling of the hand with the handle involved in using vibrating tools has a considerable impact on the stresses to which the hand-arm system is exposed. For this reason, future national and international rules and regulations on vibration assessment should take into consideration the effects of variations in coupling intensity.

Adult↗
PubMed1993

Intra-individual open comparison of burst-suppression-isoflurane-anaesthesia versus electroconvulsive therapy in the treatment of severe depression.

Isoflurane anaesthesia was proposed instead of electro-convulsive therapy (ECT) in patients with treatment-refractory depression. This open study compared burst-suppression-isoflurane-anaesthesia (BSIA) and ECT in 12 severely depressed patients. A series of 6 BSIA was administered in every patient. If improvement was insufficient or only temporary, a series of up to 12 ECT was given. A marked improvement of the depression was shown after both BSIA and ECT. Three patients were discharged from hospital after BSIA, nine patients were treated with BSIA and then ECT. The therapeutic effect of both regimens was equal as evidenced by the Hamilton-depression-rating-scale, a visual-analog-scale and the clinical global impression. BSIA requires more time and monitoring than ECT. Our exclusions of coronary, cerebral and peripheral vascular disease, untreated hypertension and focal neurological disease are strongly recommended. Due to the ease of application, ECT remains the standard treatment in depressed patients, but we consider BSIA a valuable alternative at least in patients who object to ECT.

Adult↗
PubMed1992

EEG and auditory evoked potential P300 compared with psychometric tests in assessing vigilance after benzodiazepine sedation and antagonism.

We have compared the EEG and auditory evoked wave P300 with psychometric tests in assessing vigilance after flumazenil antagonism of midazolam sedation in 12 healthy volunteers. Measurements were made before and after midazolam 0.1 and 0.2 mg kg-1 i.v., and immediately and 30, 60, 120 and 240 min after administration of flumazenil 1 mg. The sedative effects of midazolam and antagonism by flumazenil resulted in alterations in EEG, P300 and psychometric tests (syndrome short test, letter cancellation, choice reaction and recognition). However, 60 and 120 min after flumazenil a decrease in test performance indicating rebound sedation was seen only in P300 mapping. Thus P300 mapping was a sensitive method of detecting subtle differences in vigilance. Rebound sedation occurred even when midazolam 0.2 mg kg-1 was antagonized with an adequate dose of flumazenil. We suggest that it is advisable to supervise patients for at least 240 min after flumazenil antagonism of midazolam 0.2 mg kg-1.

Adult↗