A topographical study of ERP correlates of semantic and syntactic violations in the Japanese language using the multichannel EEG system.

Language processing was investigated using event-related potentials obtained using a multichannel (58-channel) EEG system, with regard to semantic dependency (i.e., selectional restriction between a verb and the arguments it takes: the SR type) and syntactic dependency between sentence-final particles and interrogative phrases (the WH-Q type) in Japanese. It was found that semantic violations elicited the conventional N400, which was distributed in the bilateral occipital and the right temporal regions, and that the syntactic violations elicited the P600 in a broad area, predominantly in the centroparietal regions. Scalp current density mappings suggested that the right temporal cortex plays a significant role in integrating pieces of contextual information, especially when it is difficult to integrate a word in the context of a sentence, and that the P600 was connected to the syntactic processes conceivably indexed by the left temporal current sink with a relatively early onset.

Synthesis and antibacterial activity of novel 1beta-methyl carbapenems with cycloalkylamine moiety at the C-2 position.

Novel 1beta-methyl carbapenems with a cycloalkylamine moiety as a side chain were synthesized and their structure-activity relationships were studied. These carbapenems showed potent antibacterial activities against a wide range of Gram-positive and Gram-negative bacteria, and moderate urinary recovery when administered intraperitoneally in mice.

Comparison of the effects of zolpidem and triazolam on nocturnal sleep and sleep latency in the morning: a cross-over study in healthy young volunteers.

1. Zolpidem (ZPD, 10 mg) was directly compared with triazolam (TRZ, 0.25 mg), a benzodiazepine hypnotic of a short action comparable to ZPD. The compounds were given to healthy young subjects for three nights, in a crossover design. 2. Polysomnographic data of three 150-min sections of the nights as well as the whole nights were analyzed, to clearly detect the proper effects of the very short acting hypnotics, which might be missed in the analysis of whole night. 3. Time courses were significantly different between the two compounds in the ratios (%) of stage wake (SW), stage 2 (S2), slow wave sleep (SWS) and stage REM (SR). 4. Compared to the baseline, SWS was increased by ZPD on the first night, not by TRZ. The separate analysis of the three 150-min sections revealed an increase of SWS during the first 150-min of the ZPD night, suggesting a proper action of ZPD to augment SWS. An increase of S2 and a decrease of SR were caused by TRZ, not by ZPD. However, the separate analysis indicated that ZPD might reduce SR during the first 150-min, which was cancelled by a subsequent rebound increase in the whole night analysis. 5. During the withdrawal period, TRZ, not ZPD, increased SW and SR with worsening of mood in the morning. ZPD did not affect sleep latency in the morning, while TRZ caused a trend of the reduction.

Comparison of the effects of zolpidem and zopiclone on nocturnal sleep and sleep latency in the morning: a cross-over study in healthy young volunteers.

Zolpidem (ZOL) and zopiclone (ZPC) are non-benzodiazepine hypnotics, with unique effects on sleep architecture compared with conventional benzodiazepines. The two compounds have different profiles in action to two major subtypes of the GABA-A receptors, therefore different effects on sleep structure may be expected. In the present study, the effects of ZOL (10mg) and ZPC (7.5mg) were compared in nine healthy young male subjects during nine-night sessions, employing a crossover design. Time courses during the sessions were significantly different between the compounds in the ratio (%) of S2 and S1. Compared to the baseline, an increase of S2 and a decrease of S1 and SR were caused by ZPC, not by ZOL. SWS was increased by both ZPC and ZOL. Significant changes by ZOL were found during the first 150-min, while changes by ZPC were mostly observed during the second 150-min. This might be related to their half-lives. ZOL did not affect sleep latency in the morning, while ZPC caused a significant decrease. Subjective sleepiness, however, was not increased in the ZPC or ZOL mornings. It was speculated that difference in the action to the GABA-A receptor subtypes might be related to the differences in the effects on the sleep architecture between the compounds.

Synthesis and biological evaluation of novel tricyclic carbapenems (trinems).

Synthesis of new tricyclic carbapenems (trinems) with a pyrrolidinyl moiety at the C-4 position of the tricyclic ring and their antimicrobial activities were studied. These trinems showed potent activities against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Among them, (4R)-[(S)-pyrrolidin-3-ylthiomethyl]trinem (14a) exhibited good activity against MRSA in vitro and in vivo.

Effects of zolpidem and zopiclone on cognitive and attentional function in young healthy volunteers: an event-related potential study.

The effects of zolpidem and zopiclone, non-benzodiazepine ultra-short-acting hypnotics, on cognitive function and vigilance level were investigated in the morning following nocturnal administration using event-related potentials (ERP) and a sleep latency test (SLT). Zopiclone significantly shortened the sleep latency the following morning, whereas zolpidem did not, perhaps due to the difference in the elimination half-lives between the compounds. No significant effect was observed for either drug on the ERP indices, including the P3, mismatch negativity and negative difference components. At a clinically prescribed dosage these sleep inducers have no remarkable effect on cognitive or attentional functions but increase sleepiness of the subjects.

Synthesis and biological evaluation of new oral carbapenems with 1-methyl-5-oxopyrrolidin-3-ylthio moiety.

The synthesis and biological properties of 1beta-methylcarbapenems with 1-methyl-5-oxopyrrolidin-3-ylthio group at the C-2 position were studied. The sodium (1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-methyl-2-[(R)-1-methyl-5-oxopyrro lidin-3-ylthio]-1-carbapen-2-em-3-carboxylate and its (S)-isomer at the 2-position show potent and well-balanced antibacterial activity. The pharmacokinetic parameters of the pivaloyloxymethyl esters of these two carbapenems were compared in mice. The in vivo potency of these carbapenems was compared with that of cefdinir. Good in vivo efficacy of these ester prodrugs reflected the high and prolonged blood levels in parent drugs achieved after oral administration to mice.

Overnight effects of triazolam on cognitive function: an event-related potentials study.

The effects of triazolam on cognitive function and vigilance on the morning following a nocturnal administration were investigated using event-related potentials (ERP) measurement and a sleep latency test (SLT). We previously reported a significant reducing effect on target N1 amplitude on the morning following triazolam administration, suggesting a residual effect of triazolam. In order to demonstrate, which aspect of cognitive function alteration caused the reducing effect on N1 amplitude, we added the ignore condition for ERP measurement, which enabled us to separate mismatch negativity (MMN) from other subcomponents overlapping N1. As a result, MMN was attenuated and sleep latency was shortened on the morning following triazolam administration. Two possibilities were suggested for the mechanism of MMN attenuation. One is GABAergic activation caused by the residual effect of triazolam per se, and the other is the lowered vigilance level demonstrated in the SLT. Further studies are necessary to determine whether this alteration in physiological bases underlying mismatch detection is specific to triazolam and/or other benzodiazepines or related to nonspecific vigilance level.

Human time production under constant routine.

Previous reports have suggested that human time production of several seconds fluctuates across the day. In order to test whether human time production was controlled by the circadian process or by the homeostatic process, we investigate diurnal fluctuation of human time production under constant routine conditions. We found a common circadian feature in time production tests of 10 s by calculating Z-score for each subject; afternoon troughs and morning peaks. These results may suggest that human time production was modulated by the circadian process.

[Drug-induced sleep disorders].

Drug-induced sleep disorders are classified into the following subtypes: a) insomnia, b) hypersomnia, c) pathological sleep d) others, those caused by medicine which can effect on circadian rhythm or sleep apnea. This paper described the relationship between several medical agents (neuroleptics, anti-depressants, anti-anxietics, anti-convulsants, psychostimulants, and drugs other than CNS-effective agents) and those effect on sleep and sleep stages. In the medicated patients, medical drugs are mainly responsible for their insomnia. However, it is sometimes difficult to find these drugs. The pathological sleep (i.e., delirium) are often developed following the drug-induced insomnia. Medication against insomnia (i.e., benzodiazepines) often exacerbates the pathological sleep. Therefore, common types of insomnia, drug-induced insomnia and pathological sleep should carefully be discriminated. Drug-induced rhythm-disorders and drug-induced sleep apnea remain to be studied. Future studies may clarify the effects of several drugs on these two disorders.

Infecciones respiratorias agudas inferiores en pacientes hospitalizados / Acute lower respiratory infections in hospitalized patients

Se estudian 216 pacientes con infecciones respiratorias agudas inferiores para determinar la eficacia del programa de Infecciones Respiratorias Agudas, aplicando las normas estandarizadas de la OMS. Se definen algunos signos de importancia diagnóstica y pronóstica (respiración rápida, tiraje, hipotermia) y se administra tratamiento de acuerdo a la etiología más frecuente de esta patología en nuestra región. Se observan factores que influyen en la presentación y pronóstico de la enfermedad como son los antecedentes (bajo peso al nacer, control prenatal, inmunizaciones, lactancia materna entre otros) y el manejo previo a la hospitalización (atención médica, uso de sintomáticos respiratorios y antibióticos). Se concluye que el programa es de fácil aplicación y funciona, debiéndose estudiar aún el manejo de las complicaciones. También se puntualiza la importancia de los signos observados y las dificultades que conlleva la asistencia previa a la hospitalización.

Effects of zopiclone, flunitrazepam, triazolam and levomepromazine on the transient change in sleep-wake schedule: polygraphic study, and the evaluation of sleep and daytime condition.

1. The effects of zopiclone 10mg (ZP), flunitrazepam 1mg (FN), triazolam 0.25mg (TZ) and levomepromazine 5mg (LP) on two models of sleep-wake schedule change-6 hours advanced shift: (A-shift), and 6 hours delayed: (D-shift)--were investigated in 6 healthy volunteers using polysomnography. 2. In A-shift with placebo, TST, SEI, %SR and REM/NREM decreased. ZP, FN and TZ shortened SL. All drugs increased TST and SEI. TZ and LP increased %SR and REM/NREM. 3. In D-shift with placebo, TST decreased, SWSL was prolonged, %S3+4 decreased, and %SR and REM/NREM increased. All drugs increased TST. ZP and LP shortened SWSL. All drugs increased %SWS. ZP, FN and TZ decreased %SR. ZP and FN decreased REM/NREM. 4. Daytime mental and physical conditions were worse than usual on more than half of the days in A- and D-shift. LP and FN caused some inadequate conditions on the following days. Significantly higher REM/NREM was observed in the nights before the days with worse mental conditions in D-shift, and lower REM/NREM in the nights before the days with worse physical conditions in A-shift. 5. It is concluded that TZ and ZP are superior to the others for A-shift and D-shift, respectively.

Electroencephalographic study of 137 patients with thalidomide embryopathy.

EEG examinations were carried out on 137 patients with thalidomide embryopathy aged between 7 and 22 with a mean age of 17.0. Waking and sleep EEGs were normal in 82 (59.9%), and abnormal in 55 (40.1%). The incidence of abnormal EEG was significantly high in the patients associated with mental retardation, and it increased in proportion to the severity of mental retardation. The most frequent abnormal EEG finding was slowing of the basic activity (35/137; 24.8%). The incidence of slowing was significantly higher in the patients with a sensorineural hearing impairment (26/74; 35.1%) than in those with dysmelia (9/62; 14.5%). Slowing appeared frequently in the patients with various cranial nerve symptoms (30/84; 35.7%). The incidence of slowing was found significantly high in the patients with borderline or subnormal intelligence (8/16; 50.0%), and it correlated with the severity of mental retardation. Many patients (48/84; 57.1%) showed unilateral or asymmetrical neurological symptoms. However, asymmetry or focal abnormality in EEG was shown in only 8 patients. Positive spikes appeared frequently in the patients with gonadal dysplasia. Other somatic symptoms, past medical history and family history were not related to the incidence of abnormal EEGs. Eight patients had had epileptic seizures prior to this examination. Another 2 patients had nocturnal enuresis and showed epileptic EEG abnormalities in this examination. The incidence of epilepsy was significantly higher in the patients we examined than among the general population. It is concluded that ingestion of thalidomide during pregnancy affected not only the morphological development of the limbs of the fetus, but the functions of its central nervous system, causing hearing impairment, other cranial nerve symptoms, mental retardation or epilepsy.

Effect of clonidine and yohimbine on sleep in man: polygraphic study and EEG analysis by normalized slope descriptors.

An all-night polygraphic study of sleep was carried out in 6 healthy volunteers acutely medicated with clonidine (225 micrograms), yohimbine (15 mg), a combination of both drugs or with placebo at random order under simple blind conditions. The conventional scoring of sleep stages was extended by an on-line analysis of the EEG according to Hjorth. Clonidine, an agonist at alpha2 receptors, induced increases of the stages 2 and 3 + 4 but a decrease of REM sleep; the reduction of the parameters mobility and complexity during non-REM sleep signified synchronization of the EEG. Yohimbine, an antagonist at the same receptor sites, enhancing noradrenaline release, increased stage 1 and REM sleep, but decreased the stages 2 and 3 + 4; increases of mobility during REM and non-REM sleep signified desynchronization. The combined treatment with clonidine + yohimbine reduced REM sleep, but not as extensively as clonidine alone; the Hjorth parameters were without significant alterations compared to placebo. The physiological hypotonia was enhanced by clonidine and the combined treatment with clonidine + yohimbine. These results favour the hypothesis of a noradrenergic facilitation of REM sleep.

[Effects of carbamazepine on EEG. Neuroendocrinological and psychometric examinations (author's transl)]. / EEG-Befunde, neuroendokrinologische und psychometrische Untersuchungen zur Carbamazepin-Wirkung.

The effects of carbamazepine on EEG, sleep-related release of growth hormone and prolactin, and on psychometric parameters were studied in ten healthy volunteers under controlled double-blind cross-over conditions. Acute application of 300 and 600 mg Tegretal resulted in constant blood levels around 3.0 and 5.5 microgram/ml respectively during the test periods of 5 and 7 h. Computerized EEG analysis according to Hjorth, revealed an occipital increase of amplitude and a decrease of mean frequency, but a frontal increase of frequency, a pattern similar to that of the tricyclic antidepressants. The polygraphic sleep pattern showed a significant decrease of sleep latency after 600 mg carbamazepine without changes of other sleep parameters. The sleep-related release of growth hormone after 600 mg carbamazepine showed a faster increase during the first sleep cycle; the profile of prolactin release, however, and the overall nocturnal secretion of both hormones were not affected. After 300 mg carbamazepine the psychometric tests revealed no significant effects on performance, but reflected an improvement of mood on self rating scales.

Dissociation of sleep stages between the two hemispheres in a case with unilateral thalamic tumor.

A case with an astrocytoma in the right basal ganglia, suspected of having originated from the posterior ventro-lateral part of the thalamus, without any clinical findings indicating severe internal hydrocephalus and cortical damaged, showed dissociation of sleep stages between the two hemispheres, i.e., the affected side always fell earlier into deeper stages of sleep and was more difficult to arouse by sonic stimulations than the other side. It is assumed that this bilateral dissociation with ipsilateral deactivation is due to the severe unilateral reduction of EEG activating influences from the brain stem and a possible functional damage to the interthalamic commissures. This finding can be explained sufficiently by recent theories based on experimental results in animals. The clinical value of this findings is also discussed in this paper.