Cerebrospinal fluid (CSF) and serum levels of interleukin-2 (IL-2), soluble IL-2 receptors (sIL-2R), neopterin, L-tryptophan (L-TRP) and beta 2-microglobulin (beta 2-M) were measured in 31 untreated multiple sclerosis patients in acute exacerbation and 27 normal controls. Twenty-six patients showed the relapsing-remitting type of disease (RRMS); 5 had a chronic-progressive course (CPMS). No changes in serum IL-2 and sIL-2R were found between RRMS patients and controls, whereas serum and CSF levels as well as the CSF/serum ratio of neopterin were significantly elevated in the RRMS group. IL-2 was not detectable in CSF of patients or controls and sIL-2R levels were at the level of the lower detection (LD) sensitivity of the ELISA method. Four of 23 RRMS patients versus 1 of 25 controls showed CSF sIL-2R levels above the LD sensitivity, indicating a trend towards elevation in acute relapse. No difference was found in serum and CSF L-TRP and beta 2-M of patients and controls. In CSF of RRMS patients neopterin and L-TRP correlated negatively, reflecting the interferon-gamma mediated activation of macrophages in acute relapse. A significant positive correlation (Spearman rank 0.57, P = 0.001) between serum IL-2 levels and duration of acute relapse (mean 30 days) warrants further evaluation.

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.

Ketamine is a racemic mixture containing equal parts of S-(+)-ketamine and R-(-)-ketamine. Their potency relation is approximately 4:1. In early human studies S-(+)-ketamine was presumed to produce the desired anaesthetic effects and R-(-)-ketamine the undesired psychic emergence reactions. Therefore, ketamine was compared in a number of randomised studies in volunteers and patients with racemic ketamine. This review addresses the impact of S-(+)-ketamine on recovery from anaesthesia, incidence and content of vivid dreams, and other side effects. The dose relation applied in the studies was 1:2. With only one exception, the recovery phase was clearly shorter after S-(+)-ketamine compared to racemic ketamine irrespective of its application as a single bolus, a bolus followed by continuous infusion, or an intramuscular injection. However, the incidence of psychic emergence reactions was lower after S-(+)-ketamine in only a single study. In conclusion, S-(+)-ketamine should be always combined with a hypnotic or sedative drug in clinical anaesthesia.

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.

No abstract

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.

No abstract

Isoflurane is the only routine volatile anesthetic which leads to a burst-suppression EEG in nontoxic concentrations and for which no memory impairments can be expected subsequent to anesthesia. After electrically induced spike-wave activity in electroconvulsive therapy (ECT), a brief period of a very flat EEG can be observed. This phenomenon may be closely related to the therapeutic effects of ECT. The results which have been achieved up to now in comparing ECT to anesthetic therapy with isoflurane, without seizures being induced, are presented.