The difficulty of diagnosing NCSE in clinical practice; external validation of the Salzburg criteria

To improve the diagnostic accuracy of electroencephalography (EEG) criteria for nonconvulsive status epilepticus (NCSE), external validation of the recently proposed Salzburg criteria is paramount. We performed an external, retrospective, diagnostic accuracy study of the Salzburg criteria, using EEG recordings from patients with and without a clinical suspicion of having NCSE. Of the 191 EEG recordings, 12 (12%) was classified as an NCSE according to the reference standard. In the validation cohort, sensitivity was 67% and specificity was 89%. The positive predictive value was 47% and the negative predictive value was 95%. Ten patients in the control group (n = 93) were false positive, resulting in a specificity of 89.2%. The interrater agreement between the reference standards and between the scorers of the Salzburg criteria was moderate; disagreement occurred mainly in patients with an epileptic encephalopathy. The Salzburg criteria showed a lower diagnostic accuracy in our external validation study than in the original design, suggesting that they cannot replace the current practice of careful weighing of both clinical and EEG information on an individual basis.     

Stereoselectivity of actions of the calcium sensitizer [+]-EMD 60263 and its enantiomer [-]-EMD 60264

The thiadiazinone derivative [+]-EMD 60263 ((+)-5-(1-(α-ethylimino-3,4-dimethoxybenzyl)-1,2,3,4- tetrahydroquinoline-6-yl)-6-methyl-3,6-dihydro-2H-1,3,4 -thiadiazine-2-on) is a Ca²⁺-sensitizing agent with only minor phosphodiesterase inhibitory activity. Our aim was to characterize the inotropic and electrophysiological effects of [+]-EMD 60263 and its enantiomer [-]-EMD 60264 in several cardiac muscle preparations. The Ca²⁺-sensitizing activity resided in the [+]-enantiomer only. [+]-EMD 60263 (3 μM) shifted the EC₅₀ of Ca²⁺ for contractile activation of skinned fibers of pig heart from 2.41 μM to 0.73 μM, whereas [-]-EMD 60264 (30 μM) was ineffective. In Langendorff-perfused guinea pig hearts, [+]-EMD 60263 and [-]-EMD 60264 induced concentration-dependent positive and negative inotropic effects, respectively; both enantiomers reduced spontaneous heart rate but did not influence perfusion pressure. The maximum increase in force of human atrial trabeculae was 35 % of pre-drug control with [+]-EMD 60263 in comparison to 113 % with forskolin. In guinea-pig papillary muscles, [+]-EMD 60263 and [-]-EMD 60264 had opposite inotropic responses, however, both agents similarly prolonged action potential duration. Both enantiomers concentration-dependently blocked the rapidly activating component I_Kr of the delayed rectifier in guinea-pig myocytes. The block saturated at potentials positive to +30 mV, closely resembling the effects of the antiarrhythmic agent E-4031 which had been originally used to define I_Kr. It is concluded, that the positive inotropic action of [+]-EMD 60263 can be explained by prevalence of the Ca²⁺-sensitizing effect. The accompanying prolongation in action potential duration is caused by block of the I_Kr component of the delayed rectifier. While the inotropic effects are stereoselective, most of the electrophysiological actions are clearly independent of sterical configuration. The combination of Ca²⁺-sensitizing with class-III antiarrhythmic action may provide an interesting pharmacological profile of potential therapeutic use. Received: 7 January 1997 / Accepted: 25 February 1997     

Spectral analysis of the electroencephalogram in neonatal rats chronically treated with the NMDA antagonist MK-801.

In order to study the involvement of NMDA-receptor activation in brain development, rat pups were chronically treated with the non-competitive NMDA antagonist MK-801 during the neonatal period. We recorded the cortical EEG at various vigilance states throughout the treatment period. Spectral analysis of the EEG showed reduced power in the delta (delta) frequency range (1.5-4 Hz) during quiet sleep and less power in the theta (theta) range (4-7 Hz) during REM-sleep in MK-801 animals than in controls. No significant differences were found for the total time spent in each of the different vigilance states. We conclude that chronic MK-801 treatment probably causes a developmental retardation in state-related brain activities.     

IN VITRO ANALYSIS OF τ PHOSPHORYLATION SITES AND ITS BIOLOGICAL ACTIVITY

INTRODUCTIONThemicrotubule－associatedprotein蚲ishyperphos－phorylatedandglycosylatedinAlzheimerdisease（AD），andtheseabnormalmodificationsformedthebasisofprogressivelyretrogradeneurofibrillarydegenerationseeninADbrainandtherebythedementia（１，２）．ADab－normallyphosphorylated蚲notonlyismicrotubuleas－semblyincompetent，butalsoinhibitsassemblyanddis－assemblesthepreassembledmicrotubulesinvitro（３）．Inthetangle－bearingneuronsinADbrain，thenormalcytoskeletonisdisruptedandreplacedwi…     

Fixation of displaced femoral neck fractures: A comparison between sliding screw plate and four cancellous bone screws

In a prospective, randomized trial, 104 consecutive patients with displaced femoral neck fractures were allocated either to fixation with a sliding screw plate or 4 ASIF cancellous bone screws. The patients were reexamined at fixed intervals to determine the time of union. The 2-year-cumulated rate of union was 64 per cent in the plate group and 84 per cent in the screw group.     

Evidence that dopamine in the nucleus accumbens is involved in the ability of rats to switch to cue-directed behaviours.

Recently we have reported that injections of d-amphetamine into the nucleus accumbens enhanced the number of switches to cue-directed behaviours without an effect on the number of switches to non-cue-directed behaviours in a swimming test. In the present study we investigated to what extent this effect is mediated via the dopaminergic system in the nucleus accumbens. For that purpose drugs selective for D1- and D2-receptors were studied in this swimming test. It was found that the selective D2-agonist LY 171 555 (50 ng/0.5 microliters) enhanced the number of different cue-directed behaviours. The selective D2-antagonist raclopride (50 ng/0.5 microliters) decreased it. Furthermore an ineffective dose of raclopride attenuated the effect of LY 171 555. Both the selective D1-antagonist SCH 23390 (400 ng/0.5 microliters) and the selective D1-agonist SKF 38393 (50-400 ng/0.5 microliters) decreased the number of different cue-directed behaviours. The effect induced by SCH 23390 could not be blocked by SKF 38393. Similarly the effect induced by SKF could not be attenuated by SCH 23390. These data point to a role for dopamine D2-receptors in the ability to switch to cue-directed behaviours. The present findings do not yet allow the conclusion that D1-receptors are involved.     

Intracardiac transplantation of a mixed population of bone marrow cells improves both regional systolic contractility and diastolic relaxation.

BACKGROUND: Pre-clinical and clinical studies suggest that transplantation of bone marrow-derived stem cells can improve global cardiac function. However, no quantitative assessment of regional systolic contraction and correlation with phenotype has been made. Therefore, we used our model of cryoinfarcted rabbit myocardium for intracardiac transplantation of a mixed population of bone marrow-derived cells and assessed both regional function and myogenic conversion of the cells. METHODS: Nineteen New Zealand white rabbits underwent cryoinjury of the left ventricle. Autologous bone marrow (BM) cells were expanded in vitro. After 2 weeks, either 1 x 10(8) mixed BM-derived progenitor cells (BM group, n = 11) or vehicle (control group, n = 8) were injected into the cryoinjured region. Regional systolic function was measured using micromanometry and sonomicrometry before and 4 weeks after cell injection; cell phenotype was evaluated histologically. RESULTS: All animals in the BM group significantly improved both systolic shortening (0.11 +/- 0.7 vs -0.05 +/- 0.05 mm in the control group, p < 0.05) and regional stroke work when compared with control (9.6 +/- 2.4 vs -1.2 +/- 1.2 mm . mm Hg, p < 0.003). In addition, the BM group had improved global diastolic function, as measured by minimum dP/dt and end-diastolic pressure. On histologic assessment, BM cells differentiated toward a myogenic phenotype. CONCLUSIONS: Transplanting a mixed population of marrow-derived cells that can adopt a myogenic phenotype improves regional contractility and diastolic relaxation after myocardial infarction.     

MRP8 and MRP14, S-100-like proteins associated with myeloid differentiation, are translocated to plasma membrane and intermediate filaments in a calcium-dependent manner

MRP8 and MRP14 are two Ca(2+)-binding proteins of the S-100 family expressed by myelomonocytic cells. Both proteins assemble to noncovalently associated complexes in a Ca(2+)-dependent manner. Members of the S-100 family are known to play a role in cytoskeletal- membrane interactions; therefore, we investigated the subcellular distribution of MRP8/MRP14 and their complexes in human monocytes. Using differential centrifugation and subsequent Western blot or enzyme- linked immunosorbent assay analysis, we found that MRP8/MRP14 were almost completely translocated from the cytoplasma to membrane and cytoskeletal structures in a Ca(2+)-dependent manner. Using a cross- linking technique, complexed forms of MRP8/MRP14 were found to be associated with the plasma membrane. Analysis of MRP-transfected L132 cells showed that the MRP8 as well as the MRP14 component of the MRP8/MRP14 complex may independently bind to membrane and cytoskeletal structures. Furthermore, immunogold electron microscopy showed a colocalization of MRP8/MRP14 and the intermediate filament type III protein vimentin in A23187-treated monocytes. Our data indicate that, in analogy to other S-100-like proteins, MRP8 and MRP14 play a role in Ca(2+)-dependent cytoskeletal-membrane interactions. Restriction of MRP8/MRP14 expression to distinct stages of myelomonocytic differentiation suggests that these proteins are involved in highly specific pathways of intracellular signaling in phagocytes.     

Hyperphosphataemia and related mortality.

Sir, With great interest we read the editorial review of Jean etal. [1] on the relationship between hyperphosphataemia and mortalityin end-stage renal disease patients. The authors summarize resultsfrom the large USRDS and DOPPS studies in which associationsof hyperphosphataemia and increased mortality risks were