Marked increase in anticonvulsant activity but decrease in wet-dog shake behaviour during short-term treatment of amygdala-kindled rats with valproic acid.

The anticonvulsant activity of valproic acid (VPA) was determined in amygdala-kindled rats after single and repeated (total of 7 injections given 3 times per day) administration of 200 mg/kg i.p. After a single injection, VPA significantly reduced the severity and duration of the kindled seizures and decreased the duration of after-discharges recorded from the stimulated amygdala, but only 12% of the animals were totally protected from seizures.

Penetration of valproate and its active metabolites into cerebrospinal fluid of children with epilepsy.

Levels of the antiepileptic drug valproate (VPA) and five of its active metabolites (2-en-VPA, 3-keto-VPA, and 3-,4-, and 5-hydroxy-VPA) were determined by gas chromatography-mass spectrometry in cerebrospinal fluid (CSF) of 15 epileptic children undergoing chronic treatment with VPA. In eight of these children, total and free drug and metabolite concentrations in plasma were also measured. All VPA metabolites present in plasma could also be detected in CSF, although concentrations were substantially lower than those of the parent compound.

Pregnancy-specific changes of antipyrine pharmacokinetics correlate inversely with changes of estradiol/progesterone plasma concentration ratios.

Antipyrine pharmacokinetics as well as estradiol and progesterone concentrations were measured in plasma of 11 healthy pregnant women during the first two trimesters and again in the same patients 6 to 20 weeks after interruption of pregnancy. During pregnancy, the clearance of antipyrine increased and its half-life decreased in all but two instances. A significant inverse relationship was found between the degree of pregnancy-specific changes of plasma clearance of antipyrine and estradiol-progesterone plasma concentration ratios: high estradiol-progesterone ratios during pregnancy corresponded to decreased plasma clearance of antipyrine; low ratios of the two hormones during pregnancy corresponded to increased plasma clearance of antipyrine.

[Drainage of cerebrospinal fluid into the renal pelvis system as a rare variant in therapy of occlusive hydrocephalus].

On the basis of two case reports it is shown that circumstances a transitory or permanent ventriculopyeloureteral CSF shunt may be indicated in the treatment of hydrocephalus. The technique is explained. The examination methods for controlling the function during the postoperative period are explained.

Pharmacokinetic aspects of drug effects in vitro (II) placental transfer to the embryo and activity of some carboxylic acids structurally related to valproic acid in whole embryos in culture.

The transfer of a group of short/medium chain-length carboxylic acids, related to the antiepileptic drug valproic acid (VPA), to the whole rat embryo in vitro was investigated. The protein binding of the drugs in the culture medium determined the placental transfer in vitro: at comparable total concentrations, the substances that bound to a lesser degree (VPA and its metabolite 2-propyl-4-pentenoic acid; 4-en-VPA) reached higher embryonic levels than the more highly bound substances, octanoic acid (OA), 2-methyl-2-ethylcaproic acid (MEC), and the VPA metabolite, 2-propyl-2-pentenoic acid (2-en-VPA). Consequently, the amount of drug added to the culture did not correlate with the transfer to the embryo, but the concentration of the free drug in the culture medium correlated highly with embryonic exposure.

Primidone and phenobarbital during lactation period in epileptic women: total and free drug serum levels in the nursed infants and their effects on neonatal behavior.

A total of 35 newborns whose mothers had been treated with either primidone (PMD), phenobarbital (PB) or a combination of one of these drugs with other antiepileptic drugs were included in this study. Fetal/maternal serum concentration ratios at birth, milk/serum concentration ratios and neonatal half-lives were determined for PMD, PB and phenylethylmalondiamide (PEMA). Steady-state serum levels of PMD in 2 nursed infants were 2.

Neuropathological findings in lesions of the optic nerve of different etiologies.

Cases of optic nerve lesions of various origins are described. These were seen in a systematic study of 59 autopsy cases with underlying neurological or neurosurgical diseases. The characteristic morphological signs of direct and indirect as well as primary and secondary lesions are discussed.

Embryotoxic effects of thalidomide derivatives on the non-human primate Callithrix jacchus; 3. Teratogenic potency of the EM 12 enantiomers.

The teratogenic potencies of the enantiomers of 2-(2,6-dioxopiperidine-3-yl)-phthalimidine ( = EM 12), a teratogenic thalidomide analogue, were investigated in Callithrix jacchus, a primate very sensitive to the teratogenic action of this thalidomide analogue. The results indicate that the S-(-)-form of EM 12 is clearly more teratogenic than the R-(+)-form. The interpretation of the studies designed to evaluate stereo-selective differences in the teratogenicity of the enantiomers becomes difficult, since both enantiomers racemise in vivo with appreciable rates (Schmahl et al.

The enantiomers of the teratogenic thalidomide analogue EM 12: 1. Chiral inversion and plasma pharmacokinetics in the marmoset monkey.

The plasma pharmacokinetics of the enantiomers of 2-(2,6-dioxopiperidine-3-yl)-phthalimidine (EM 12) and the racemic mixture of this substance were investigated in Callithrix jacchus, a thalidomide-sensitive primate. Single doses of 5 mg/kg body wt were administered orally or intraperitoneally. Maximum plasma concentrations were reached 1 h after administration of the enantiomers, and 3 h after application of the racemate.

Transplacental pharmacokinetics of teratogenic doses of etretinate and other aromatic retinoids in mice.

The transplacental pharmacokinetics of single teratogenic doses of etretinate and motretinide were compared with particular emphasis on distribution and concentrations in the exposed embryos of the free acid metabolite, etretin. The three aromatic retinoids were also tested for their direct inhibitory effect on chondrogenesis in the limb bud mesenchymal cell "micromass" culture assay. After a standard dose of 100 mg/kg administered on day 11 of gestation in NMRI mice, all three compounds were teratogenic, but they differed from each other in potency.

[Validity of the electroencephalogram and evoked potentials in the diagnosis of brain death].

Alterations of electroencephalogramm and evoked potentials in brain dead patients are known. We are going to discuss the value of the various parameters as well as their comparison with the clinical symptoms. Newer guidelines recommend the brain-stem acoustic evoked responses, too.

[Ventriculo-renal shunt in the therapy of hydrocephalus].

Ventriculo-atrial shunt has proved to be an effective therapy for hydrocephalus. We report about two patients, in whom due to different causes this therapy was not possible. Both of them were treated with ventriculo-pyeloureterostomy for liquor drainage.

Valproic acid-induced neural tube defects: reduction by folinic acid in the mouse.

Neural tube defects were induced dose-dependently by single injections of the anticonvulsant drug valproic acid (VPA) as sodium salt in mice on gestational day 8. Folinic acid (5-CHO-THF) coadministration by i.p.

Cadmium concentrations in milk and blood of smoking mothers.

Cadmium concentrations were measured by flameless atomic absorption spectrometry in blood and mature milk of 15 nonsmoking and 56 smoking mothers during the nursing period. Both blood and milk concentrations increased with increasing cigarette consumption. The median blood and milk concentrations in nonsmokers were 0.

Low teratogenicity of 13-cis-retinoic acid (isotretinoin) in the mouse corresponds to low embryo concentrations during organogenesis: comparison to the all-trans isomer.

13-cis-Retinoic acid (isotretinoin) is teratogenic in man at therapeutic doses (0.5-1.5 mg/kg body wt), but only marginally teratogenic in the mouse at exceedingly high doses (greater than 100 mg/kg).

[Evoked potentials in intracranial operations: current status and our experiences].

Intraoperative neuromonitoring, especially evoked potential monitoring, has gained interest in recent years for both the anesthesiologist evaluating cerebral function and the neurosurgeon wishing to avoid neuronal lesions during intracranial operations. Before evoked potential monitoring can be introduced as a routine method of intraoperative management, experience with this method particularly in intensive care units, is imperative. We recorded evoked potentials with the Compact Four (Nicolet) and Basis 8000 (Schwarzer Picker International) computer systems.

Smoking and passive smoking during pregnancy and early infancy: effects on birth weight, lactation period, and cotinine concentrations in mother's milk and infant's urine.

The extent of smoke exposure via mother's milk and passive smoking was investigated in a prospective, longitudinal matched-pair study by comparison between children, whose mothers smoked substantially throughout pregnancy and nursing period and children whose mothers did not smoke. Our preliminary results show that not only infants of smoking mothers but also those of smoking fathers show reduction of birth weight. Smoking mothers weaned their babies earlier than non-smokers.

Ventral duplication of the autopod: chemical induction by methoxyacetic acid in rat embryos.

Administration of 2-methoxyethanol to pregnant rats on day 12 of gestation induced ventral duplication of the autopod, presumably via its oxidative metabolite, methoxyacetic acid. Morphological observations indicate that the limb bud periderm is severely damaged by methoxyacetic acid so that large patches of this structure are actually missing during an extended period of limb bud development. A high concentration of methoxyacetic acid (10 mM) was found in the extraembryonic fluid and we postulate that the damage to the periderm was initiated from this extraembryonic exposure.

Spinal cord compression by extensive epidural lipoma. A case report.

A 48-year-old man had a 3-year history of progressive sensory and motoric disturbance of the lower extremities. Computed tomography and magnetic resonance imaging revealed an extensive epidural lipoma reaching from T2 to T10 level. After hemilaminectomy the dorsally located epidural fat was removed.

Multimodality evoked potentials and electroencephalography in severe coma cases. Clinical experiences in a neurosurgical intensive care unit.

In a neurosurgical intensive care unit 26 patients with unconsciousness and unresponsiveness were investigated by means of multimodality evoked potentials and electroencephalography in order to obtain information on the functional state of the nervous system. Multimodality evoked potential techniques allowed us to differentiate patients with EEG alterations due to drug treatment from those without therapy. The functional state and prognosis can be better evaluated by means of evoked potential techniques.