Differential modulation of the short- and long-latency somatosensory evoked potentials in a forewarned reaction time task.

OBJECTIVE: We investigated modulation of the short- and long-latency somatosensory evoked potentials (SEPs) in a forewarned reaction time task. METHODS: A pair of warning (auditory) and imperative stimuli (somatosensory) was presented with a 2 s interstimulus interval. In movement condition, subjects responded by grip movement with the ipsilateral hand to the somatosensory stimulation when the imperative stimulus was presented. In counting condition, they silently counted the number of imperative stimuli. The SEPs in response to the imperative stimuli were recorded. RESULTS: Frontal N30 and central N60 amplitudes were significantly smaller in the movement than in the counting or rest conditions. None of the short-latency components differed between the counting and rest conditions. In contrast to the short-latency components, P80 was significantly larger in the counting than in the rest condition, and showed a further increase from the counting to the movement condition. The N140 amplitude was significantly larger in the movement than the rest condition, but was not changed between the counting and the rest conditions. CONCLUSIONS: The attenuation of the frontal N30 and central N60, and the enhancement of the P80 and possibly the N140 resulted from the centrifugal mechanism. The present findings may show the different effects of voluntary movement on the early and subsequent cortical processing of the relevant somatosensory information requiring a behavioral response. SIGNIFICANCE: The present study demonstrated the differential modulation of short- and long-latency components of SEPs in a forewarned reaction time task.     

Intra-arterial ACNU chemotherapy employing 20% mannitol osmotic blood-brain barrier disruption for malignant brain tumors.

The clinical effects and problems of intra-arterial water-soluble antitumor nitrosourea (ACNU) therapy following osmotic blood-brain barrier modification are discussed. Twenty-one patients with malignant brain tumors were divided into two groups. Group 1 consisted of 16 patients treated by operation, irradiation, and two or more courses of intracarotid infusion of ACNU 100 mg/body (1.7-2.2 mg/kg) following 20% mannitol 200 ml (1.3-1.6 ml/sec) (7 grade 4 astrocytomas, 5 grade 3 astrocytomas, and 4 others). Group 2 consisted of five patients treated by operation, irradiation, and repeated intracarotid infusion of ACNU 100 mg/body alone (grade 4 astrocytoma). The 2-year survival rate in Group 1 was 79% (11 of 14 cases followed up for longer than 2 years) and the 3-year survival rate was 67%. Five of seven grade 4 astrocytoma patients (71%) in Group 1 survived for more than 1 year 6 months, whereas four of five grade 4 astrocytoma in Group 2 died within 1 year 6 months. The measurement of the ACNU concentration in tumor tissues and blood in 11 brain tumors, after intracarotid infusion of ACNU with blood-brain barrier disruption, showed peak values in the tumor tissues of 3.02-32.53 micrograms/gm (mean, 9.67 micrograms/gm), about three to five times as high as that in blood in most cases. This method used in Group 1 appears to be relatively safe without permanent neurological deficits and offers a potential therapeutic effect when used in combination with appropriate premedication in suitable patients.     

The tight junction component protein, claudin-4, is expressed by enteric neurons in the rat distal colon

The expression of a tight junction (TJ) component protein, claudin-4, in the enteric neurons was investigated in the rat distal colon by immunohistochemistry and RT-PCR. Claudin-4 immunoreactivity was detected in almost all neurofilament-positive enteric neurons both of the submucosal and the myenteric plexuses, and both of the cell bodies and the neurofibers. The immunoreactivity of enteric neurons for claudin-4 was divided into two types: strongly and weakly positive neurons. Especially in the myenteric plexus, the stained neurons were classified by Dogiel's morphological classification of enteric neurons. The strongly stained claudin-4 positive neurons show Dogiel type II morphology, while the weakly stained claudin-4 positive neurons show Dogiel type I morphology. These immunohistochemical data were supported by mRNA expression in the muscle plus submucosa preparation containing the submucosal and myenteric plexuses, as well as mucosa preparation. The physiological function of claudin-4 expressed on enteric neurons is unclear up to now. It is however suggested that claudin-4 expressed on enteric neurons might play roles for the neural activity, for example as insulation between neurofibers. In conclusion, the present study clearly shows that claudin-4 is expressed by enteric neurons. This is the first evidence that the neuron itself expresses the TJ component protein, claudin-4, in the nervous system.     

Anxiety in school refusal children with indefinite complaints: psychological estimation using State-Trait Anxiety Inventory and therapy by serotonin reuptake inhibitors

Using State-Trait Anxiety Inventory (STAI) we examined 13 junior high school students with school refusal and indefinite complaints. Significant increase of the anxiety levels was higher in these children than in the control group. Serotonin reuptake inhibitors (SSRIs) were administered to 19 elementary and junior high school students with school refusal and indefinite complaints. The indefinite symptoms improved markedly in 2 children, moderately in 11, and mildly in 6. We conclude that high anxiety may cause indefinite symptoms in children with school refusal and that the treatment of indefinite symptoms with SSRI is an effective supportive therapy.     

Impact of diabetes and Krebs von den Lungen‐6 on coronavirus disease 2019 severity: A single‐center study from Japan

Aims/IntroductionDiabetes mellitus is reported as a risk factor for increased coronavirus disease 2019 (COVID‐19) severity and mortality, but there have been few reports from Japan. Associations between diabetes mellitus and COVID‐19 severity and mortality were investigated in a single Japanese hospital.Materials and MethodsPatients aged ≥20 years admitted to Osaka City General Hospital for COVID‐19 treatment between April 2020 and March 2021 were included in this retrospective, observational study. Multivariable logistic regression analysis was carried out to examine whether diabetes mellitus contributes to COVID‐19‐related death and severity.ResultsOf the 262 patients included, 108 (41.2%) required invasive ventilation, and 34 (13.0%) died in hospital. The diabetes group (n = 92) was significantly older, more obese, had longer hospital stays, more severe illness and higher mortality than the non‐diabetes group (n = 170). On multivariable logistic regression analysis, age (odds ratio [OR] 1.054, 95% confidence interval [CI] 1.023–1.086), body mass index (OR 1.111, 95% CI 1.028–1.201), history of diabetes mellitus (OR 2.429, 95% CI 1.152–5.123), neutrophil count (OR 1.222, 95% CI 1.077–1.385), C‐reactive protein (OR 1.096, 95% CI 1.030–1.166) and Krebs von den Lungen‐6 (OR 1.002, 95% CI 1.000–1.003) were predictors for COVID‐19 severity (R ²= 0.468). Meanwhile, age (OR 1.104, 95% CI 1.037–1.175) and Krebs von den Lungen‐6 (OR 1.003, 95% CI 1.001–1.005) were predictors for COVID‐19‐related death (R ²= 0.475).ConclusionsDiabetes mellitus was a definite risk factor for COVID‐19 severity in a single Japanese hospital treating moderately‐to‐severely ill patients.     

MCNU delivery into malignant brain tumor and normal brain tissue by intravenous or intraarterial infusion

In 13 Fischer 344 rats transplanted intracerebrally with 9 L gliosarcoma, 13 normal Fischer 344 rats and 4 clinical cases of malignant glioma, a new water-soluble nitrosourea (MCNU) was given and the concentration was measured in blood, tumor tissues, normal brains around the tumors and normal hemispheres by intravenous or intraarterial infusion of MCNU. At 5 min. after administration of MCNU 20 mg/kg (4-5 mg/body) in 9 L gliosarcoma bearing Fischer rats, mean MCNU concentration in the blood was not different between 20 micrograms/ml intravenous and 23 micrograms/ml intraarterial administrations whereas that in the tumor tissues by intracarotid infusion of MCNU was 40 +/- 14.4 micrograms/g which was about two times as much as 22.9 +/- 8.13 micrograms/g by intravenous infusion of MCNU. Mean MCNU concentration of normal brains around tumor tissues was 2.49 micrograms/g in intravenous and 8.95 micrograms/g in intracarotid infusion. MCNU concentration of tumor tissues in 4 cases of malignant gliomas was higher by intracarotid administration than by intravenous administration compared to that in the blood. Maximum tumor/blood ratio of MCNU was 1.94 in intracarotid administration for the malignant glioma. It is suggested that intraarterial administration was more useful than intravenous infusion as an administration route for malignant brain tumors.     

Remote facilitation of supraspinal motor excitability depends on the level of effort

Stretch reflexes and motor-evoked potentials (MEPs) of a muscle are facilitated when performing intensive contraction of muscles located in a different segment (remote effect). We investigated to what extent the remote effect on MEPs in the flexor carpi radialis (FCR) in humans is modulated during sustained maximal and submaximal voluntary contractions of the ipsilateral quadriceps (remote muscle). We found that even when the force of maximal voluntary contraction (MVC) of the remote muscle declined during sustained MVC, the magnitude of the remote effect on MEPs remained constant. Maximal electrical stimulation of the remote muscle and transcranial magnetic stimulation of the corresponding motor cortex revealed that the level of voluntary activation gradually decreased during the sustained MVC. The motor response in the FCR following magnetic stimulation at the level of the foramen magnum, which preferentially elicits muscle response as a direct response of the corticospinal tract, was not modified by the remote effect during the sustained MVC. This finding suggested that the excitability of the spinal motoneuron pool remained constant. In contrast to the sustained MVC, during sustained submaximal contraction of the remote muscle, the magnitude of the remote effect on MEPs gradually increased as muscle fatigue developed. These findings suggest that the remote effect on MEPs was dependent on the level of effort driving the remote muscle, but not on the actual level of force output of the remote muscle, and that the origin of the remote effect was supraspinal, putatively upstream of the primary motor cortex.     

Effect of zotepine on head-twitch induced by L-5-hydroxytryptophan, mescaline and 2,5-dimethoxy-4-methylamphetamine in mice and rats

The effect of zotepine, a new neuroleptic, on head-twitch induced by L-5-hydroxytryptophan (L-5HTP), mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM) in mice and rats was compared with that of known neuroleptics and the serotonin receptor blocker cyproheptadine. Among the neuroleptics tested, zotepine and haloperidol produced potent inhibitory effects on head-twitch induced by these three drugs. The results indicate that zotepine has a potent anti-hallucinogenic effect.