Sudden death of a volunteer.

A volunteer participating in a study of eproxindine, a new antiarrhythmic agent, had a sudden cardiorespiratory arrest and died. Subsequently it became known that he had received a depot injection of flupenthixol on the day before his death; an interaction between these two drugs seems likely. This incident illustrates that it is impossible to guarantee absolute safety in volunteer studies if details of medical history are withheld.

Pharmacokinetics and tolerance of enoxacin in healthy volunteers administered at a dosage of 400 mg twice daily for 14 days.

Twenty-four subjects participated in this placebo-controlled, double-blind study. Eighteen were randomized to receive active enoxacin capsules (400 mg twice daily for 14 days) and the remaining six received placebo therapy. Steady state was reached in four days or less, with an average minimum concentration of 1.

Acetylcholinesterase and polyingression in the epiblast of the primitive streak chick embryo.

Cholinesterase histochemistry and SEM were performed on whole chick blastoderms, stage 4 Hamburger-Hamilton, to study the relationship between acetylcholinesterase (AChE) and cell movement in the epiblast. Correlation of LM photomicrographs of enzyme sites with SEM micrographs of surface topography permitted the determination of the three dimensional morphology of enzyme-positive cells. On the epiblast under surface two cell configurations were observed indicating movement of cells out of the epiblast at sites distant to the streak.

Ro 15-1788 antagonizes the effects of diazepam in man without affecting its bioavailability.

In a double-blind, placebo-controlled three-way cross over study, the efficacy of Ro 15-1788 200 mg, a new benzodiazepine antagonist, in blocking the amnesic, cognitive, psychomotor and subjective effects of diazepam 20 mg, was investigated in a group of six healthy male volunteers. The amnesic effects of diazepam were markedly attenuated by the combined administration of Ro 15-1788. The psychomotor and subjective effects of diazepam by mouth were most pronounced 2.

The effect of PK5078, a new serotonin uptake inhibitor, on serotonin levels and uptake in human platelets, following administration to healthy volunteers.

PK 5078 is a recently developed compound which inhibits specifically the neuronal reuptake of serotonin and enhance its release. PK 5078 was administered to healthy male volunteers in single and multiple oral doses and the effects on platelet serotonin uptake and content were examined. A significant dose-related inhibition of 3H-serotonin uptake by platelets was observed following single oral doses of PK 5078 (25-150 mg), with maximal inhibition at 75 mg.

Platelet uptake of serotonin following repeated administration of 3-cyano-imipramine to healthy volunteers.

In a double blind, placebo-controlled study the effects of daily oral administration of 3-cyano-imipramine on the 3H-serotonin uptake capacity of platelets were investigated in healthy volunteers. The initial dose was 1 mg, rising to 3 mg daily for 7 days. A rapid and profound inhibition of 3H-serotonin uptake was observed in platelets isolated from the treated subjects.

Absence of central effects in man of the benzodiazepine antagonist Ro 15-1788.

The benzodiazepines are typified by a profile of side effects which includes drowsiness, ataxia and incoordination. Ro 15-1788, an imidazodiazepine derivative, exhibits marked antagonism of the behavioural and biochemical effects of the benzodiazepines in animals and man. It is devoid of any behavioural activity in animals, except at very high doses.

Effects of a single oral dose of 3-cyano-imipramine on serotonin uptake and content of platelets in healthy volunteers.

Changes in platelet serotonin uptake and content were investigated following administration of a single oral dose of 3-cyano-imipramine to healthy volunteers. The uptake of 3H-serotonin by platelets harvested from these subjects was almost completely inhibited 4 h after dose administration. This inhibition continued for at least 24 h.

RO 15-1788 antagonises the central effects of diazepam in man without altering diazepam bioavailability.

1 In a double-blind, placebo controlled study, the efficacy of Ro 15-1788, a new benzodiazepine antagonist, in blocking the cognitive, psychomotor and subjective effects of diazepam, was investigated in a group of six healthy male volunteers. 2 The central effects of orally administered diazepam (40 mg) were most pronounced 1 h after dosing and persisted for 9 h with decreasing severity. 3 Concurrent oral administration of Ro 15-1788 (200 mg) completely prevented the impairment in cognitive and psychomotor function observed after diazepam alone.

In vitro studies of amphibian gastrula cells.

Experiments are presented to determine whether Rana pipiens gastrula cells differentiate in vitro as they do in vivo with respect to rate, morphology and spreading characteristics. Comparisons are made between presumptive germ layer cells isolated at late blastula, cultured for 24 h, and the same cell types form late gastrula cultured for 1 h (LeBlanc and Brick, 1981a). These cells are chronologically similar and should be morphologically similar at the end of their respective culture periods if in vivo and in vitro differentiation are proceeding in the same direction and rate.

Primary hypoblast development in the chick : II. The role of cell division.

Proliferative patterns in colchicine treated embryos during the first few hours of incubation, Eyal-Giladi and Kochav stages XI-XIII, clarify the role of cell division in the anterolateral expansion of the primary hypoblast as well as the expansion of the entire blastoderm. A layer of primary hypoblast (extra-embryonic endoderm) can form in the absence of cell division. Colchicine, in concentrations used here, does not prevent ingression of cells from the upper layer to the primary hypoblast and establishment of intercellular contacts.

Primary hypoblast development in the chick : I. Scanning electron microscopy of normal development.

Scanning electron microscopy (SEM) indicates that the primary hypoblast forms beneath the area pellucida during the first 8 h of incubation mainly by establishment of contact among cells which move downward out of the epiblast. This movement, polyingression, begins posteriorly and continues antero-laterally during the period of primary hypoblast formation. Polyingression produces many pits and possibly a crescentic fold in the embryo upper surface with corresponding cell clusters and a ridge on the lower surface.

Etretinate in treatment of actinic keratosis. A double-blind crossover study.

50 patients with actinic keratosis were studied over four months of treatment with either etretinate ('Tigason') or placebo. Each treatment was given for two months and the order of administration was randomised. The clinical response to treatment was assessed by direct measurement and photographs of the lesions at monthly intervals.

Calcium and spreading behaviour of amphibian blastula and gastrula cells.

Cell locomotion involves several structural-functional activities: membrane extensibility, microfilament regulation and adhesive interactions. There is evidence for Ca2+ requirement in all of these. Our data may clarify the role of Ca2+ in locomotion and adhesion.

Morphologic aspects of adhesion and spreading behavior of amphibian blastula and gastrula cells.

By means of SEM we have examined spreading and adhesive behavior of cells isolated from superficial and deep regions of germ layers from blastula to late gastrula in Rana pipiens embryos. Each of the cell populations sampled show adhesive and spreading characteristics distinctive for each region and stage which we interpret as demonstrating the following: (1) From blastula through late gastrula, cells from each region have already acquired the ability to express surface morphologic and adhesive features independently of their association with their neighbors, i.e.