Shortening of distal motor latency in anode distal stimulation.

OBJECTIVE: Distal motor latency (DML) is shortened when the anode is held distally instead of the cathode by increasing the stimulus intensity. The objective of this study was to clarify the mechanism responsible for this shortening. METHODS: In seven healthy subjects, compound muscle action potential (CMAP) was obtained from the thenar muscle by bipolar stimulation of the median nerve at the wrist, and the intensity at which the first motor units were stimulated was defined as the threshold. Bipolar stimulation with extended interpole distance was employed to identify the generating site of the CMAP and F-wave. RESULTS: The shortening of DML was dependent on the stimulus intensity and threshold. For the low threshold condition, the CMAP generating site was replaced from the proximal cathodal pole to the distal anodal pole by increasing the stimulus intensity. The generating site of the F-wave remained at the proximal cathodal pole irrespective of stimulus intensity. CONCLUSIONS: Replacement of the generating site results in the shortening of DML. When the F-wave is recorded after being induced by anode distal stimulation, CMAP should not be simultaneously evaluated. SIGNIFICANCE: This study clarified the generation sites of CMAP and the F-wave when induced by anode distal stimulation.

Significance of lung resistance-related protein in the clinical outcome of acute leukaemic patients with reference to P-glycoprotein.

Lung resistance-related protein (LRP) overexpression in leukaemic blast cells from acute leukaemia patients and the effect of LRP or P-glycoprotein (P-gp) on the clinical outcome of acute leukaemia were investigated individually by dividing patients into four groups. The complete remission rate of group I (LRP and P-gp both negative) was 81.7%, group II (only LRP positive) 87.5%, group III (only P-gp positive) 87.1% and group IV (LRP and P-gp both positive) 40.0%. There were no statistical differences between group I and groups II or III, but a significant difference was observed between groups I, II or III and group IV. Median overall survival in group IV was significantly shorter (4.6 months) than in groups I, II or III, although no significant differences were observed between group I and groups II or III (18.9, 20.5 and 31.8 months). There was a tendency for disease-free survival in group III to be longer than that in groups I, II or IV. The reasons for these findings are discussed. Our present results indicate that the co-existence of LRP and P-gp strongly influenced the effectiveness of induction chemotherapy and long-term prognosis, whereas the isolated presence of LRP or P-gp did not.

[An autopsy case of an extensive epidural spinal abscess demonstrating necrotizing poliomyelopathy].

A 59-year-old man with a history of diabetes mellitus (NIDDM) presented with fever, back pain and weakness in the left lower limb. Three weeks later he suddenly developed flaccid paraklegia, a sensory deficit below the abdomen and sphincter dysfunction. MR images of the spinal cord showed an extensive anterior spinal epidural abscess extending from the seventh cervical to the twelfth thoracic spine and osteomyelitis in the lower thoracic spines. He died of pulmonary infection one year after the disease onset. Postmortem examination revealed a large empyema in the lung. On neuropathological examination, small multiple hemorrhagic or ischemic lesions were found in the basal ganglia and the pons. The spinal cord was markedly atrophic in the lumbar cord. However, there was neither compression deformity in the cord nor occlusion in the anterior spinal artery. Throughout the thoracic cord, rarefaction and focal cavity formation was selectively present in the gray matter, particularly the posterior horns. In the white matter, vacuolar changes were seen peripherally as well as Wallerian degeneration in the lateral and anterior corticospiral tracts and in the fascicles gracilis bilaterally. The mechanisms inducing the cord damage in cases of epidural spinal abscess have been speculated to be either direct compression by the abscess or the secondary circulatory disturbance in the cord due to compression. In our case, the cord showed necrotizing poliomyelopathy, which was similar to that of ischemic myelopathy found in the cases of cardiac arrest or dissecting aneurysm of the aorta. Autopsy study of spinal cord lesion associated with epidural abscess has been limited in number and our case should contribute to the understanding of the pathomechanism of such myelopathy.

Voltage-clamp analysis of taurine-induced suppression of excitatory postsynaptic potentials in frog spinal motoneurons.

1. The depressant actions of taurine applications on lumbar motoneurons in the isolated frog spinal cord were studied using conventional intracellular recordings and the two-electrode voltage-clamp technique. 2. With microelectrodes containing K+-acetate, 0.75-2 mM taurine mostly induced a hyperpolarization that often faded or turned into depolarization during the continuous application. A higher concentration (5-7.5 mM) depolarized a majority of cells. The effects on the membrane potential were associated with an increase in input conductance (approximately 285%). 3. The reversal potential of the taurine-induced currents was approximately -70 mV, with microelectrodes containing K+-acetate. In recordings using KCl-filled electrodes, taurine (less than or equal to 2 mM) produced a large depolarization (greater than or equal to 20 mV) at resting potentials near -50 mV, thereby indicating that the reversal potential was positively shifted by loading the cell with Cl-. These results suggest that the taurine potentials were mediated predominantly by an increased Cl- permeability. 4. Voltage-dependent relaxations of taurine currents were observed in 10 of 14 neurons. 5. A linear relation was found between the input conductance and the amount of current required to generate a 1-mV increment in EPSP at resting potential. 6. Polysynaptic excitatory postsynaptic potentials (EPSPs) and currents (EPSCs) were more susceptible to taurine than the monosynaptic responses. Taurine (less than 1 mM) seemed to suppress the interneurons mediating polysynaptic pathways. 7. Monosynaptic EPSPs and EPSCs were decreased with higher concentrations of taurine (greater than 1 mM). The percent reduction of EPSPs and that of the corresponding EPSCs had a positive correlation (r = 0.95), whereas, there was no significant correlation between changes in EPSPs and in input conductance, and between changes in EPSCs and in input conductance. The amount of current required to produce a 1-mV increment of EPSP was increased in the presence of taurine, in association with the increased input conductance. 8. Taurine suppressed synaptic potentiation of EPSPs evoked by paired stimuli, at an interval of 60-180 ms. Gamma-D-glutamylglycine, an antagonist of receptors for excitatory amino acids, greatly reduced the amplitude of EPSPs, but had little effect on synaptic potentiation. 9. Taurine suppressed glutamate currents evoked at membrane potentials, clamped near rest in low Ca2+, high Mg2+ solution. 10. These findings suggest that the taurine-induced reduction of EPSPs is due mainly to suppression of EPSCs, through both presynaptic and postsynaptic mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)

Excitatory postsynaptic currents in response to different synaptic inputs of frog spinal motoneurons.

Excitatory postsynaptic currents (EPSCs) evoked by the primary afferents (dorsal root; DR) and the descending lateral column (LC) fibers were studied in frog spinal motoneurons under voltage clamp with two separate electrodes. The average rise time and half-width of the EPSCs were shorter for LC-EPSCs than for DR-EPSCs, though the values of the parameters for LC- and DR-EPSCs were distributed within a similar range. The relation between the amplitudes of the EPSP and EPSC was almost linear. The amount of current required to generate a 1 mV increment in the EPSP was 5.0 +/- 2.3 nA for the DR-EPSC and 3.8 +/- 1.2 nA for the LC-EPSC. The decay time was shortened by hyperpolarization and prolonged by depolarization in DR- and LC-EPSCs and spontaneous EPSCs. The reversal potential ranged from -30 to -5 mV and was almost identical for DR- and LC-EPSCs and spontaneous EPSCs in individual motoneurons. The current-voltage relation was linear from -100 to +50 mV for these EPSCs. Spontaneous EPSCs became more prominent and frequent during a large hyperpolarization or a large depolarization. These results suggest that the ionic mechanisms underlying EPSC are similar for the functionally different excitatory synapses located on motoneurons.

Responses of intracranial pressure (ICP) produced by stimulating the pressor area in the brainstem at various levels of blood pressure and ICP in cats.

An increase in intracranial pressure (ICP) was produced by stimulating brainstem pressor sites in cats anesthetized with alpha-chloralose. The ICP responses were augmented by lowering prestimulus BP and reduced by elevating prestimulus BP. In contrast, stimulus-induced pressor response of BP showed no consistent correlation to prestimulus BP. When the mean amplitude of stimulus-induced ICP responses at the control prestimulus ICP (within 18 mmHg) was plotted against the mean of the prestimulus BP levels for each site examined, the sites were classified into 2 groups by the regression line; sites generating a marked ICP response above the line and those generating a small ICP response on and under the line. The former sites were located in the paramedian region of the reticular formation including nuclei parvocellularis and gigantocellularis. The latter sites scattered throughout the brainstem pressor area. The ICP response at the former sites was markedly increased at an elevated prestimulus ICP. The peak ICP response at 30-50 mmHg of prestimulus ICP was 70-100 mmHg, similar to plateau waves. The ratio of ICP response size to BP response size was negatively correlated to prestimulus BP and the regression line was 2-5 times steeper at an elevated prestimulus ICP (18-60 mmHg) than at the control ICP. On the other hand, the negative relation between the response ratio and the BP for the latter sites produced no such change at the increased prestimulus ICP. These findings suggest that the ICP response is produced primarily by neurogenic intracranial vasodilation, which works most effectively at moderately decreased cerebral perfusion pressure. This mechanism may be involved in a series of events that results in plateau waves.

Changes in intracranial pressure and arterial blood pressure following electric stimulation to restricted regions in the cat brainstem.

The brainstem of anesthetized cats was electrically stimulated to examine the changes in the intracranial pressure (ICP). There were pressor and depressor sites, which preferentially produced an immediate increase and decrease in ICP in association with the arterial pressor and depressor responses, respectively. A preferential increase in ICP was also observed by stimulation of some depressor sites. The stimulus-induced ICP responses were usually different from the secondary ICP changes due to nonneurogenic alteration of arterial blood pressure (BP) as evoked by arterial bleeding and infusion of saline solution; the stimulus-induced increase in ICP was greatly enhanced when the stimulation to the pressor sites was applied at lowered BP levels and at moderately elevated ICP levels. In addition, when a gradual elevation in ICP was spontaneously observed with the lowering of the BP level, the pressor site-induced increase in ICP exceeded 70-100 mmHg at the peak plateau-like waves, regardless of the magnitude of accompanying arterial pressor response. We propose that the stimulus-induced ICP responses cannot be explained merely by the metabolic changes, the decreased intracranial compliance, and the secondary transmural action on the intracranial space of the arterial pressor and depressor responses. A neurogenic mechanism that directly affects intracranial blood diameter may be involved in the ICP responses, especially those observed at a lower BP level, in addition to extracranic action of sympathetic and parasympathetic nerve activities.