A prospective randomised trial on the effect of monitoring plasma anticonvulsant levels in epilepsy

Summary To evaluate whether knowledge of plasma levels of anti-epileptic drugs has an effect on therapeutic outcome, 127 epileptic outpatients were randomly assigned to two groups (A and B). Plasma levels of group A were reported to the treating physician who attempted to keep the plasma levels within the therapeutic range. The treating physician was not informed of the results of plasma lavel determinations of group B. Data from 105 patients were available for assessment at the end of the study year. Therapeutic results of groups A and B were not significantly different. The reduction in seizure frequency was associated with an increase in plasma concentrations of the anti-epileptic drugs. Thus, under the conditions of the study, knowledge of plasma levels of anti-epileptic drugs did not further improve therapeutic results.

---

Zusammenfassung Um festzustellen, ob die Kenntnis des Plasmaspiegels der Antiepileptika das Therapieergebnis verbessern kann, wurden 127 ambulant behandelte Patienten mit Epilepsie in randomisierter Reihenfolge in zwei Gruppen eingeteilt (A und B). Die Plasmaspiegel der Antiepileptika in Gruppe A wurden dem behandelnden Arzt mitgeteilt, der versuchen sollte, die Plasmaspiegel in den Therapeutischen Bereich zu bringen. Die Ergebnisse der Plasmaspiegelbestimmung in Gruppe B (Kontrollgruppe) wurden dem behandelnden Arzt nicht mitgeteilt. Am Ende des Untersuchungsjahres konnten die Daten von 105 Patienten ausgewertet werden. Das Behandlungsergebnis von Gruppe A und von Gruppe B war am Ende des Beobachtungsjahres nicht signifikant verschieden. Die Abnahme der Anfallshäufigkeit ging mit einem Anstieg der Plasmakonzentration der Antiepileptika einher. Somit konnte unter den Bedingungen dieser Studie das Therapieergebnis durch die Kenntnis der Plasmaspiegel der Antiepileptika nicht weiter verbessert werden.

     

Variability in behavioral responses to benzodiazepines in the rat

The effects of chlordiazepoxide (10 mg/kg) were assessed in a holeboard by the reductions in head-dipping, rearing and locomotor activity; the correlations among all these measures were significant. Test-retest correlations were significant for all but the time spent head-dipping. On the basis of their behavioral responses to chlordiazepoxide six "strong" and six "weak" responders were identified and used for an in vitro electrophysiological study. There were no differences between the two groups in the extent to which flurazepam potentiated muscimol, but picrotoxin showed a greater antagonism of muscimol in slices from "strong" responders and flurazepam showed a greater reduction of picrotoxin potency. There was a significant correlation between the in vitro picrotoxin shift and the chlordiazepoxide-induced reduction in locomotor activity. The correlations between behavioral responses to chlordiazepoxide and the plasma benzodiazepine concentrations were low and only one (for locomotor activity) reached significance.     

Interactions of halogenated industrial chemicals with transthyretin and effects on thyroid hormone levels in vivo

Previous results in experimental systems have suggested that hydroxylated PCBs may decrease thyroid hormone levels through associative interaction with transthyretin. In the present paper it was investigated whether this property was also shared by various industrial chemicals, mainly pesticides. In total, 65 compounds from 12 chemical groups were analyzed for direct interference with the T4 binding site of transthyretin using a competitive binding assay. Sixty per cent of the compounds were competitive at a concentration level of 100 M. Relatively strong interactions were observed by several chlorophenols, chlorophenoxy acids and nitrophenols, as well as by individual compounds such as hexachlorobenzene, dicofol, bromoxynil and tetrachlorohydroquinone. Examples from these chemical groups, e.g. pentachlorophenol, 2,4-dichlorophenoxybutyric acid, dinoseb and bromoxynil, also reduced plasma TT4 levels in rats. In addition, bromoxynil decreased plasma TT3 levels. The results suggest the existence of a number of halogenated industrial chemicals with a potential for lowering plasma thyroid hormone levels through interference with hormone transport carriers.     

Plasma folate levels in preterm infants,with and without a 1 mg daily folate supplement

One hundred and four preterm infants were studied during the first few months of life in the Special Care Baby Unit of Addenbrooke's Hospital, Cambridge, United Kingdom. Previously, it had been the daily practice within the Unit to give a 1 mg oral supplement of folate (in the form of pteroylglutamic acid), once the infants had commenced full enteral feeding. At least one blood sample was obtained from 70 infants before oral folate supplementation was started. In these, the plasma folate levels fell progressively from a median value of 45 g/l to a median of 12 g/l, by the 2nd–3rd week of life. Once started on the oral supplement, 83 of the infants provided at least one blood sample. The plasma folate level of these infants rose immediately to a median value of 300 g/l and a maximum of 1000 g/l. Within individuals, these plasma folate levels decreased progressively following the introduction of the supplement, despite continuing daily supplementation. In a typical baby this decrease appeared to be explained by an increase in body-size, i.e. dilution of the folate into a larger pool. The implications of this level of supplementation are discussed, and in the light of our observations we suggest that daily supplementation in the range, 0.05–0.2 mg folate may be preferable for well preterm infants.     

Plasma catecholamines and oxygen consumption during weaning from mechanical ventilation

Previous studies on oxygen consumption ( ) during weaning from mechanical ventilation assumed that an increase in ( ) reflected oxygen consumption by respiratory muscles ( ), and proposed as a weaning predictor. We measured CO₂ production ( ) and plasma catecholamines in 20 short-term ventilated patients during weaning by SIMV and CPAP. as a percentage of during spontaneous ventilation ( %) ranged from 4.8% to 41.5%. also increased and correlated with . Plasma adrenaline and noradrenaline increased significantly to levels known to produce considerable increases in metabolic rate. Mean arterial pressure and heart rate concomitantly increased, but spontaneous minute ventilation decreased. Thus, since the increased plasma catecholamines are calorigenic, the assumption that represents is incorrect. Although mean % of successfully weaned patients was significantly less than that of failure-to-wean patients, the wide scatter of individual values in the latter group excludes % as an accurate weaning predictor.     

Chemical modification of membrane proteins by brominated taurodehydrocholate in isolated hepatocytes; relationship to the uptake of cholate and of phalloidin and to the sensitivity of hepatocytes to phalloidin

Summary In vitro treatment of isolated rat hepatocytes with brominated taurodehydrocholic acid (BTC) reduced their sensitivity against phalloidin and inhibited the uptake of phalloidin as well as of cholate in an irreversible and concentration dependent manner. BTC was taken up itself by liver cells; this process was inhibited by 4,4-diisothiocyano 2,2-stilbene disulfonate (DIDS).When hepatocytes were incubated with ³⁵S-BTC their plasma membranes contained five labeled protein species with molecular weights of 67,000, 49,000, 38,000, 32,000 and 24,000 as shown by SDS-electrophoresis. No marked difference was observed when isolated plasma membranes from livers were directly treated with the affinity label. DIDS suppressed covalent binding of ³⁵S-BTC to membrane components drastically. Incubation of phalloidin insensitive AS-30D ascites hepatoma cells with ³⁵S-BTC did not result in a chemical modification of the above five proteins. This agrees with an earlier observation that hepatoma cells are unable to take up phalloidin and bile acids (Petzinger et al. 1979; Rufeger and Grundmann 1977; Kroker et al. 1978).Abbreviations used BTC brominated taurodehydrocholic acid - ³⁵S-BTC ³⁵S labeled brominated taurodehydrocholic acid - DIDS 4,4-diisothiocyano 2,2-stilbene disulfonate - [³H]DMP [³H]demethylphalloin This work was supported by the Deutsche Forschungsgemeinschaft     

Tryptophan tolerance and metabolism in endogenous depression

The concentration of free and total tryptophan and kynurenine in plasma from 49 female depressives and 26 female controls was measured following oral loading with l-tryptophan, 100 mg/kg body weight. There was no significant difference between five depressives and six controls in the area under curve for free or total tryptophan or kynurenine in plasma. The peak concentration of kynurenine occured 4 h after loading and it correlated significantly with the area under curve for kynurenine. There was no significant correlation between the l-tryptophan dose (g) and the plasma concentration of kynurenine at 4 h in the 49 depressives or 26 controls. The mean plasma levels of tryptophan and kynurenine at 4 h in the depressives were not significantly different from control levels. There was no clear relationship between the plasma levels of tryptophan or kynurenine at 4 h and the therapeutic response in 13 depressives treated with l-tryptophan for 14 days.It is concluded that the absorption, the plasma clearance, and the degradation to kynurenine of loading doses of l-tryptophan are normal in depressed patients. Results further-more suggest that the plasma levels of tryptophan and kynurenine at 4 h are poor predictors of the response to l-tryptophan treatment in depressives.     

Enhanced neophobia but normal plasma corticosterone levels in rats with dorsal noradrenergic bundle lesions

The effects of dorsal noradrenergic bundle (DNB) lesions on plasma corticosterone levels were determined in male albino rats. DNB lesions did not affect baseline plasma corticosterone levels. Furthermore, the increased corticosterone levels produced by various environmental manipulations did not differ between control and DNB lesioned groups. However, the lesioned group did exhibit longer latencies to eat familiar food in novel environments, as well as to eat novel foods in a familiar environment. Latencies to eat novel food in novel environments did not differ between the two groups and this was attributed to a "ceiling" effect. These endocrinological data fail to support the hypothesis that the enhanced "neophobia" observed in DNB lesioned rats is due to an increase in the intensity of the emotional reaction to novel stimuli. The data do not preclude the possibility, however, that the enhanced neophobic reactions reflect impaired habituation to these stimuli.     

The clinical effect and the effect on serum IgG antibodies to peripheral nerve tissue of plasma exchange in patients with Guillain-Barré syndrome

Summary The mixed haemagglutination technique was used to demonstrate IgG antibodies to peripheral nerve tissue in sera from patients with the Guillain-Barré syndrome. The clinical effect and the effect on the antibodies of plasma exchange were examined in 18 patients. Neurological examination with muscle testing and neurophysiological examination of the patients were performed before and immediately after plasma exchange. Before the exchange antibodies were detected in sera from 11 of the patients. These patients showed clinical improvement during the treatment. After plasma exchange, antibodies were detected in sera from only two of the patients. The seven patients without detectable antibodies showed no clinical improvement.

---

Zusammenfassung Bei 18 Patienten mit Guillain-Barré Syndrom, die einem therapeutischen Plasmaaustausch (PA) unterzogen wurden, wurde das Serum mit Hilfe einer gemischten Hämagglutinations-Technik auf IgG-Antikörper (IgG-AK) gegen peripheres Nervengewebe untersucht. Einfluß der PA auf den klinischen Zustand und Titerverlauf wurden verglichen: Bei 11 Patienten wurden IgG-AK gefunden; sie zeigten unter der PA eine klinisch verifizierte Besserung, die in einigen Fällen auch elektromyographisch gesichert werden konnte; nach Beendigung der PA waren nur noch in 2 Fällen IgG-AK nach-weisbar. Bei den restlichen 7 Patienten fehlten IgG-AK; bei ihnen war die PA ohne Effekt.