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Biomedical subjects

R Kaji

Publications and source records attributed to R Kaji.

At least 73 records · Page 4Linked to original sources

[Diagnosis and treatment of multifocal motor neuropathy (Lewis-Sumner)].

We made a retrospective long-term follow-up study of 25 patients with multifocal motor neuropathy (Lewis-Sumner). The diagnosis was based upon criteria modified from those of AAEM (Sumner 1997). The electrophysiological findings indicating conduction block or focal demyelinative lesions were more diagnostic than anti-GM 1 antibody titers, which were elevated in only 40% of these patients. Demonstration of definite conduction block was not always possible in those patients who responded favorably to intravenous immunoglobulins (IVIg), whereas indirect pieces of evidence such as F-wave abnormalities or focal conduction delay or dispersion were equally helpful. IVIg had superior outcome to cyclophosphamide, which sometimes caused serious adverse effects. Three patients with severe axonal involvement showed elevated monospecific antibodies to GalNAc-GD1a.

Adolescent↗

[Treatment of hemifacial spasm with type A botulinum toxin (AGN 191622): a dose finding study and the evaluation of clinical effect with electromyography].

Forty-one patients with hemifacial spasm had an injection of type A botulinum toxin (AGN 191622; Allergan Co. Ltd., Irvine, CA). Patients were randomly divided into 3 groups by the injection dose: group L (1 unit; 14 patients), group M (5 units; 14 patients), and group H (10 units; 13 patients). Half of the dose was injected into the orbicularis oculi and the rest into the zygomaticus major muscles on the affected side. The clinical effect and electromyogram were evaluated at 2 weeks after the injection. The clinical benefit was dependent on the injection dose, and group H showed the highest rate of improvement (84.6%). No adverse effect related to the toxin was demonstrated except one patient in group H who showed mild and transient lagophthalmos. For 81.8% of group H patients, the final judgement was "useful" or "very useful", which was 9.1% for group L and 50.0% for group M. On the other hand, electromyography disclosed no consistent dose-finding relationship. We conclude that at least 10 (preferably more) units of botulinum toxin are necessary for effectively treating hemifacial spasm. Electromyography has only limited value for the evaluation of clinical effect.

Botulinum Toxins, Type A↗

[Torsion dystonia].

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Botulinum Toxins↗

Effect of ultrahigh-dose methylcobalamin on compound muscle action potentials in amyotrophic lateral sclerosis: a double-blind controlled study.

To develop a symptomatic treatment for amyotrophic lateral sclerosis, we compared the effects of ultrahigh-dose and low-dose (25 and 0.5 mg/day, intramuscularly, for 14 days) methylcobalamin on averaged compound muscle action potential amplitudes (CMAPs) in a double-blind trial. No significant changes in CMAP amplitude were found in 12 patients who had the low-dose treatment at either 2 or 4 weeks after start of treatment. By contrast, 12 patients assigned to the ultrahigh-dose group demonstrated a significant increase at 4 weeks. This method may provide a clinically useful measure to improve or retard muscle wasting, if a larger extended trial fulfills its promise.

Action Potentials↗

Muscle afferent block for the treatment of oromandibular dystonia.

Oromandibular dystonia is a focal dystonia involving the masticatory and tongue muscles, causing difficulties in speech or mastication. We treated 13 patients with this condition by injecting diluted lidocaine and alcohol intramuscularly. This method is aimed at reducing muscle spindle afferent activity. The symptoms had been resistant to other therapies such as pharmacotherapy or dental treatment. All patients showed clinical improvement after this therapy with reduced EMG activities in the affected muscles, whereas control injection of normal saline gave no changes in EMG activities. The overall subjective improvement was 57.7 +/- 25.1% (mean +/- standard deviation) in a self-rating scale. The mean response of the jaw elevator muscles (70 +/- 13.1%) was significantly higher (p < 0.02, t test) than that of the depressor muscles (38 +/- 28.4%). Despite the precise mechanism being unknown, this difference might be related to the smaller number of muscle spindles in the depressor than the elevator muscles. This therapy is useful for the treatment of drug-resistant oromandibular dystonia.

Adult↗

cis-Diamminedichloroplatinum and 5-fluorouracil are potent inducers of the cytokines and natural killer cell activity in vivo and in vitro.

It has been reported that certain chemotherapeutic agents exhibit effects that enhance the antitumor host responses in the patients with malignant diseases. In the present study, we investigated whether cis-diamminedichloroplatinum (cisplatin) and 5-fluorouracil (5-FU) may induce cytokines and effector cells with antitumor efficacy in vivo and in vitro. The cultivation of human peripheral blood mononuclear cells (PBMC) in the presence of cisplatin (0-1.0 microg/ml) or 5-FU (0-5.0 microg/ml) resulted in the significant augmentation of natural killer (NK) and lymphokine-activated killer (LAK) cell activities as well as generation of interferon (IFN) gamma, tumor necrosis factor (TNF) alpha, beta interleukin(IL)-1beta, IL-6 and IL-12 in vitro. In addition, all of these activities were almost completely neutralized by addition of anti-asialoGM1 antibody and complement (P < 0.05). In an in vivo model, the administration of anti-asialoGM1 antibody significantly shortened the survival time extended by the treatment with cisplatin or 5-FU (P < 0.05), both on nude mice bearing salivary gland tumors and on syngeneic MethA-tumor-bearing BALB/c mice. Furthermore, high levels of NK and LAK activities and significant increases of the numbers of cells positive for asialoGM1, IFNgamma, TNFalpha, or IL-1beta were detected in the spleen cells derived from animals given cisplatin or 5-FU as compared with those given saline (P < 0.001-0.05). These findings clearly indicate that cisplatin and 5-FU are potent inducers of several types of cytokines and effector cells carrying antitumor activity mediated by asialoGM1-positive cells (mainly NK cells) for the most part, and that these abilities are closely associated with the in vivo antitumor effect of these agents.

Adenocarcinoma↗

Dissociation between contingent negative variation (CNV) and Bereitschaftspotential (BP) in patients with parkinsonism.

In order to clarify the generator mechanism of the late component of contingent negative variation (CNV), we compared the late CNV with Bereitschaftspotential (BP) in patients with parkinsonism (Parkinson's disease and progressive supranuclear palsy). In patients with mild symptoms (Hoehn Yahr grade I and II) both the late CNV and BP were clearly seen. In patients with severe symptoms (Hoehn Yahr grade III, IV and V) the BP was normally seen, but the late CNV was significantly smaller or absent (P < 0.001 at Cz) and it was also significantly smaller than that obtained from age-matched normals. In one patient (H-Y grade II) who had normal BP, the late CNV was diminished selectively at the midline area. Since it was reported that the late CNV arises from at least the supplementary motor area (SMA), selective diminution of the late CNV at the midline could be explained by the decreased activity of the SMA in parkinsonism. It was also previously reported that the BP was absent but the late CNV was normally present in a patient with cerebellar efferent lesion (Ikeda et al., 1994). Taken together with the experimental results indicating that movement-related neurons in the putamen behave contingent on external stimuli, it is suggested that subcortical generating mechanism is different for the late CNV and BP although both commonly share at least some cortical generators, and that the basal ganglia are most likely responsible for the generation of the late CNV and the cerebellar efferent system for the generation of the BP.

Adult↗

The physiological effect of anti-GM1 antibodies on saltatory conduction and transmembrane currents in single motor axons.

Anti-ganglioside (anti-GM1) antibodies have been implicated in the pathogenesis of Guillain-Barré syndrome, multifocal motor neuropathy and motor neuron diseases. It has been held that they may interfere with saltatory conduction by blocking sodium channels. We tested this hypothesis by analysing action potentials from 140 single nerve fibres in 22 rat ventral roots using external longitudinal current measurement. High-titre anti-GM1 sera from Guillain-Barré syndrome or multifocal motor neuropathy patients, or anti-GM1 rabbit sera were applied to the rat ventral root, where saltatory conduction in single motor fibres was serially observed for 4-12 h (mean 8.2 h). For control experiments, we also tested anti-galactocerebroside (anti-GalC) sera, which causes acute demyelinative conduction block, and tetrodotoxin (TTX), a sodium channel blocker. Conduction block was found in 82% of the fibres treated with anti-GalC sera and 100% treated with TTX, but only in 2% (one out of 44) treated with the patients' sera and 5% (two out of 38) treated with rabbit anti-GM1 sera. All the nodes blocked by anti-GM1 sera revealed intense passive outward membrane current, in the internode just beyond the last active node. This pattern of current flow was similar to that in fibres blocked by demyelination with anti-GalC sera, and quite different from that seen in fibres blocked by reducing sodium currents with TTX. Our findings suggest that anti-GM1 sera neither mediate conduction block nor block sodium channels on their own. We conclude that physiological action of the antibody alone is insufficient to explain clinically observed conduction block in human diseases.

Action Potentials↗

Abnormal sensorimotor integration in writer's cramp: study of contingent negative variation.

To investigate the pathophysiology of idiopathic focal dystonia, we recorded contingent negative variation (CNV) as a physiological index of sensorimotor integration in 14 right-handed patients with writer's cramp and compared it with normative data. CNV was recorded in the S2 choice reaction time paradigm: Two kinds of auditory S2 (Go or No-Go) were given 2 s after the auditory S1, and the subject reacted only to the Go signal by extending the wrist. In normal subjects, the late CNV amplitude had no difference at Cz between left- and right-hand tasks and was symmetric without significant amplitude laterality irrespective of the side of hand movement. In patients with writer's cramp, the late CNV amplitude at Cz was relatively larger for the left-hand task than the right-hand task (p < 0.03), and a significant amplitude laterality of the late CNV (larger on the right) was present especially at the central area for the right-hand task (p < 0.03). Since the late CNV is known to be generated, at least in part, from primary and supplementary motor cortices, the significant laterality of the late CNV seen with the right-hand task in patients with writer's cramp might represent functional abnormality of motor cortices possibly as the result of basal ganglia function.

Adult↗

Abnormal excitability of the corticospinal pathway in patients with amyotrophic lateral sclerosis: a single motor unit study using transcranial magnetic stimulation.

The pathophysiology of corticospinal tract degeneration in amyotrophic lateral sclerosis (ALS) was investigated by studying the effect of transcranial magnetic stimulation on discharge characteristics of single motor units during voluntary activation. The motor units were recorded from the first dorsal interosseus muscles of 12 patients with ALS, 14 healthy subjects, 12 patients with upper motor neuron lesions and 9 with pure lower motor neuron diseases. More than 100 magnetic stimuli were delivered over the scalp during minimal muscle contraction. The occurrence of motor unit discharges was plotted in a peristimulus time histogram. An increase in discharge probability at latencies of 20-30 msec, that represents monosynaptic activation (primary peak) was found in normal units. Motor units from ALS patients with short disease durations had significantly increased discharge probabilities in the primary peak (P < 0.001). Motor units from 4 ALS patients with upper motor neuron signs showed double primary peaks: an initial synchronized peak followed by a dispersed peak. The latter was ascribed to a slow corticospinal pathway, which remains undetected or is functionally insignificant in healthy subjects. We conclude that the excitabilities of the surviving corticospinal tract pathways are abnormally increased in ALS, especially in the early stage.

Adolescent↗