Biomedical subjects
Publications and source records attributed to T Shibazaki.
In 16 cases of stereotactic deep brain biopsy, a correlative study was made by computer tomography, positron emission tomography, and electrophysiological depth recording. This multimodal study is shown to be of great value in stereotactic biopsy of deep-seated cerebral lesions.
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The authors report the results of a long-term follow-up study of the effects of the physiologically defined selective VIM (nucleus ventralis intermedius)-thalamotomy on tremor of Parkinson's disease in 27 patients and essential tremor in 16 patients. The follow-up period ranged from 3.25 to 10 years (mean 6.58 years). In 43 patients a total of 50 operations (including four bilateral operations and three reoperations) were carried out. The early (2 to 4 weeks after surgery) and late effects on the tremors were determined clinically and electromyographically. Fourteen parkinsonian cases were treated with minimal lesions (about 40 cu mm). Their late results were very similar to the early results: in 10, the tremors were completely abolished, three had a slight residual tremor, and one underwent reoperation 3 months after the first surgery. Eleven essential tremor cases were treated with minimal lesions. Six of these tremors were completely abolished, four patients had slight residual tremors, and one patient with a recurrence underwent reoperation 2 years after the initial surgery. In these 23 successful operations with minimal lesions (excluding two cases with reoperation), the tremor was abolished without discernible long-lasting side effects. The other 23 operations on 16 patients with Parkinson's disease (including one reoperation) and on seven with essential tremor (one of whom also had a minimal lesion on the other side) involved relatively large lesions. In this group, the surgery was successful in almost every case. It was concluded that radiographically and physiologically monitored selective VIM-thalamotomy for parkinsonian and essential tremor is effective even when lesioning is minimal. Moreover, the beneficial effect is maintained over a long period of time.
Thirteen patients with tremor after stroke were treated by stereotactic thalamotomy. Prior to making therapeutic lesions, microrecordings were tried and the findings were compared with our own results obtained in Parkinson's disease. Several characteristic features were revealed in terms of changes in electrical activity in and around the thalamic Vim nucleus. These findings support the idea that reorganization of the thalamic sensory nuclei might take place.
The Vim nucleus of the human thalamus is the cell sparse zone. The neurons in this zone respond to peripheral stimuli of kinesthetic modality with a short latency. In the cytometrical study, the cell sparse zone is identifiable in both the monkey and cat thalamus. The cell dimension and density in a 1 mm2 area in the cell sparse zone of each species are as follows: humans--large neuron 500-900 microns2, medium neuron 200-400 microns2, cell density 60-90/mm2/50 microns thickness; monkeys--large neuron 400-800 microns2, medium neuron 200-400 microns2, cell density 120-250/mm2/50 microns thickness; cats--large neuron 400-800 microns2, medium neuron 200-400 microns2, cell density 120-250/mm2/50 microns thickness. In this zone, there are large and medium thalamocortical relay neurons defined by the Golgi impregnated and HRP studies. It is still obscure which neurons respond to kinesthetic stimulation and which neurons or afferent fibers play important roles in the tremor mechanism.
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To evaluate the effect of the physiologically defined selective Vim-thalamotomy on tremor type Parkinson's disease (PA, 26 cases) and essential tremor (ESS-T, 16 cases), a long-term follow-up study was conducted. The follow-up time extended from 4 months to 7 years (mean: 3.6 years). On 42 cases a total of 49 operations (4 bilateral surgery and 3 reoperations) were carried out. After identifying kinesthetic neuron, the coagulative lesion was made by using Leksell's apparatus between two needles of 4 mm effective tip length located with 3 mm interval including the recording point. One coagulation (unit lesion) destroyed about 20 mm3 brain tissue taking account of the mechanical damage by the needles themselves. The unit lesion was added around an imaginary cylinder of 3 mm radius, until the tremor was abolished completely. On the basis of number of unit lesion and its extent within an imaginary cylinder, these 49 operations were divided into the following group. Group I (minimal lesion group): coagulative lesion of 1 to 3 units within a quadrant of the imaginary cylinder. Group II: 3 to 5 units within 1/2 to one cylinder. The early (14 days after operation) and the late results on the tremor were evaluated clinically and electromyographically by 4 different categories: complete abolition, slight residual, residual, and recurrence in a strict sense. The late results in 13 PA cases of group I (similar to the early results) were: 10 complete abolition, 2 slight residual and one recurred, this case was reoperated 3 months after first operation and therefore categolized in group II. The late results in 11 ESS-T cases of group I were: 6 complete arrest, 4 slight residual, and one recurred case, which had been reoperated 2 years after operation. Therefore in a total of 24 minimal lesioned cases with PA and ESS-T complete abolition in 16, slight residual in 6, and 2 reoperated cases. In these successful 22 cases with minimal lesion, the tremor was abolished without noticeable long-lasting side effect. In other 20 cases with PA and ESS-T of group II, the tremor was almost completely relieved and maintained. In conclusion, by radiographically and physiologically controlled selective Vim thalamotomy for Parkinsonian and essential tremor, it was shown that the effect of minimal lesion was valid and well maintained on the long-term follow-up base.
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Bioavailabilities of three commercially available tablets and two trial tablets of nalidixic acid were determined. The correlation between in vivo bioavailability parameters and in vitro dissolution rates derived by eight methods (oscillating basket I and II, beaker I, II, and III, rotating basket, paddle and rotating flask) is discussed. Nalidixic acid and its metabolite, 7-hydroxynalidixic acid, were determined in serum by HPLC with a strong anion-exchange resin column. All parameters for nalidixic acid bioavailability showed significant differences among the tablets tested. The relationship between Cmax and AUC was not linear but concave. However, Cmax decreased linearly in proportion to the delay of Tmax. The rank order of tablets according to bioavailabilities was just the same as the rank order obtained when comparing dissolution rates determined by any of the above methods, with the exception of one tablet which had a poor disintegrating ability. The parameters for the rate of bioavailability (Cmax and Tmax) showed good linearity with 1/T50 determined by all of the methods. However, AUC showed significant correlation with neither T50 nor 1/T50.
The bioavailability of nalidixic acid in beagles was determined using the same tablet formulations previously tested on humans and was compared with bioavailability in humans and with in vitro dissolution rates. The beagle bioavailability test provided lower power in all of the bioavailability parameters than did the human test. Tmax of the tablets did not greatly differ in beagles, although in humans a wide variation of Tmax was seen. A linearity between Cmax and AUC0-infinity was observed in beagles, but Tmax did not show a linearity with Cmax or AUC in dogs, which is quite different from the relations observed in humans. The rank order of tablets according to Cmax was exactly the same between humans and beagles. AUC also showed the same rank order between humans and beagles except for on tablet with a poor disintegrating ability. A significant correlation between human and beagle Cmax values was obtained (r = 0.8952; p less than 0.05), but not between human and beagle AUC and Tmax values.
The aim of the present study was to determine the identity of the neurotransmitter released by the pathway from the subthalamic nucleus to the entopeduncular nucleus in the rat, using extracellular stimulating and recording techniques and microiontophoresis. In order to avoid stimulation of passing fibers at the level of the subthalamic nucleus, (collaterals to the entopeduncular nucleus of the caudato-nigral pathway, or direct projections to the entopeduncular nucleus from the substantia nigra or nucleus tegmenti pedunculopontinus), the experiments were performed in rats bearing chronic ipsilateral lesions in order to make these pathways degenerate. Under such conditions, subthalamic nucleus stimulation suppressed the spontaneous firing of all the entopeduncular nucleus cells studied (n = 40) for 15-25 ms (mean duration +/- S.E.M.:21.88 +/- 1.57 ms). Entopeduncular nucleus cells were identified by antidromic activation from the ventral anterior thalamic nucleus (40%) or lateral habenula nucleus (68%). Low doses of iontophoretically applied GABA (60 cells) or glycine (15 cells) were inhibitory upon entopeduncular cells, while acetylcholine or carbamylcholine were poorly excitatory (18 cells), or had no effect (28 cells). The subthalamic nucleus-evoked inhibition of entopeduncular neurons was reversed by microiontophoretically applied bicuculline or picrotoxin, at doses which blocked the GABA-induced response, but not that produced by glycine or acetylcholine. With similar experiments, strychnine and atropine were ineffective. This excludes a possible role of glycine or acetylcholine in the subthalamic-evoked inhibitory response of entopeduncular cells. The present study strongly suggest that GABA is a neurotransmitter in the inhibitory subthalamo-entopeduncular pathway.