Tetanus toxin produces neuronal loss and a reduction in GABAA but not GABAB binding sites in rat hippocampus.

The neuropathological effects of tetanus toxin, microinjected in the rat CA1 hippocampal area, were studied by using a microscopical and autoradiographical approach. Tetanus toxin produced a dose- and time-dependent neuronal loss in the CA1 area accompanied by a reduction in the binding of gamma-[3H]aminobutyric acid ([3H]GABA) to GABAA but not GABAB sites in the pyramidal cell layer.

Pharmacokinetics in pregnancy and placental drug transfer.

Total body water increases in pregnancy and while the uterus, placenta, fetus, and amniotic fluid constitute part of this increase, the largest component is in the extracellular water. Fat stores also increase and thus the distribution volumes of all drugs expand, but the major effect is seen in polar drugs which are confined to the extracellular space. Cardiac output and renal function also increase and elimination of polar drugs is accelerated.

Signal processing technique to extract neuronal activity from noise.

A method of extracting extracellularly recorded action potentials from background electronic noise is described. Segments of traces containing stimulus-induced activity are Fourier transformed and the increase in the total power density over that of control noise segments is used as a measure of stimulus-induced neuronal activity. We show first, with observations from the amphibian visual system and mammalian auditory system, that our technique yields similar quantitative information to that obtained from the conventional spike counting method when the recording arrangement is optimal.

Phenytoin kinetics during pregnancy and the puerperium.

During pregnancy changes in maternal physiology and plasma composition may alter drug binding and dose requirements. We have measured plasma unbound and total phenytoin, and saliva concentrations at intervals in 11 pregnant epileptics. Plasma albumin concentrations were also measured in pregnant and non-pregnant women.

Extracorporeal circuit sequestration of fentanyl and alfentanil.

Fentanyl or alfentanil, in doses approximating to those used in clinical practice, was added to the priming fluid of an extracorporeal circuit before the institution of cardiopulmonary bypass (CPB). The concentrations of both drugs in the priming fluid were measured over a 20-min period. The concentration of fentanyl decreased at neutral or high pH values, suggesting drug adsorption to the circuit.

Placental transfer of anticonvulsants in the rabbit: the effect of maternal protein binding and fetal flow.

The fetal-to-maternal ratios of carbamazepine, antipyrine and phenytoin are principally determined by maternal protein binding, though greater lipid solubility may enhance the transfer of valproate compared to that of other drugs at high flows. Placental clearance of all anticonvulsants showed flow-dependent characteristics. This is in line with our findings for basic drugs.

Transfer of fentanyl across the rabbit placenta. Effect of umbilical flow and concurrent drug administration.

The transfer of fentanyl has been studied in the perfused in situ rabbit placenta. Does were infused with fentanyl and, subsequently, with fentanyl plus bupivacaine and pethidine. Antipyrine was infused throughout as an index of materno-fetal exchange.

[Connective tissue reinforcing structures of the digital tendon sheaths of the human hand].

At a greater number of humid preparated human hands, all the ligamentous supports of the digital tendon sheath were exposed and their dimensions were determined. The osteofibrous channels, which contain the long flexor tendons of the digits, were bounded on the one hand by transversely concave shaft areas of the phalanges and the palmar ligaments and on the other side by the fibrous parts of the tendon sheath. From the second to the 5th finger, it has a regular extension of length, which begins proximal at the heads of the metacarpal bones and runs distal to the base of the nail phalanx.

Epidural fentanyl in labour. An evaluation of the systemic contribution to analgesia.

In a randomized double-blind trial in the first stage of labour, 20 patients given fentanyl 80 micrograms in the epidural test dose of bupivacaine, were compared with 20 patients receiving an intravenous infusion designed to produce comparable plasma fentanyl concentrations, at the same time as their epidural test dose. Despite slightly higher plasma fentanyl concentrations in the intravenous fentanyl group, epidural fentanyl produced analgesia which was more complete, more rapid in onset and slightly longer lasting. Supplementary doses of bupivacaine were needed to produce analgesia in 75% of the intravenous and 30% of the epidural fentanyl group.

The effect of airway anaesthesia on the control of breathing and the sensation of breathlessness in man.

The effect on ventilation of airway anaesthesia, produced by the inhalation of a 5% bupivacaine aerosol (aerodynamic mass median diameter = 4.77 micron), was studied in 12 normal subjects. The dose and distribution of the aerosol were determined from lung scans after the addition to bupivacaine of 99mTc.

Do saliva concentrations predict plasma unbound theophylline concentrations? A problem re-examined.

On the assumption that plasma unbound drug concentrations are therapeutically active, the value of saliva concentrations in predicting plasma unbound theophylline concentrations was investigated in 25 ambulatory adults (aged 27 to 84 years) receiving theophylline (225-1350 mg aminophylline daily) for asthma or chronic bronchitis. Plasma samples from all patients were ultrafiltered, and the plasma unbound theophylline (F) concentrations were compared with the corresponding total plasma (P), citric acid stimulated saliva (S) and non-stimulated saliva (Ns) theophylline concentrations. Plasma unbound theophylline concentrations correlated significantly with P (r = 0.

The place of saliva in antiepileptic drug monitoring.

It has previously been shown that saliva phenytoin concentration bears a constant relationship to plasma free concentration whether protein binding of phenytoin is normal or disturbed by other drugs, pregnancy, renal failure, or hypoalbuminaemia. The present work examines the relationship between saliva (S), plasma free (F), and plasma total (P) concentrations of other anticonvulsants in 100 epileptic patients. Mean S/P ratios were for phenobarbitone 0.

Epidural versus intramuscular fentanyl. Analgesia and pharmacokinetics in labour.

In a randomised double blind trial, 36 patients in the first stage of labour received either epidural or intramuscular fentanyl at the same time as the epidural test dose of bupivacaine. Analgesia was more rapid in onset and more complete in the epidural fentanyl group. Supplementary doses of bupivacaine were required within the first hour in 62% of the intramuscular fentanyl group compared with only 16% in the epidural group.

In vivo procedures for assessment of hair greasiness.

Synopsis Greasy hair is a common problem in Europe. The first step in developing anti-grease hair products must be to establish a sensitive protocol for measuring any changes in perceived hair greasiness. Sensitive clinical trials and in vivo evaluation methods of determining hair greasiness have been developed that show significant differences in the perceived hair greasiness following the use of different shampoos.

Simplified intravenous nutrition using Intralipid-based mixtures in patients with serious gastrointestinal disease.

An Intralipid-based intravenous feeding mixture has been given to 20 patients with serious gastrointestinal disease who required parenteral nutritional support (mean duration 13.75 days). In half of the patients, only peripheral veins were used for infusion (mean duration 12 days), the infusion site being changed every 24-48 hr.

Phenytoin-valproate interaction: importance of saliva monitoring in epilepsy.

Sodium valproate is often used with phenytoin when epilepsy cannot be controlled by a single drug. Sodium valproate depresses phenytoin protein binding and so invalidates plasma phenytoin monitoring as a means of determining precise phenytoin dosage requirements. Plasma and saliva phenytoin and plasma valproate concentrations were measured in 42 patients with epilepsy receiving both drugs.