Acute and Subacute Effects of Diazepam on Psychomotor Skills: Interaction with Alcohol

Abstract Effects of diazepam and alcohol on psychomotor skills were measured in two trials. In the first one, 200 healthy students volunteered for a double-blind single-dose study. Three doses of diazepam (5, 10 and 20 mg) and alcohol (0.5, 0.8 and 1.2 g/kg) were used alone and combined to construct dose-response graphs. All doses of alcohol impaired divided attention while co-ordinative skills were impaired by the 1.2 g/kg dose. Diazepam alone did not impair reactive or co-ordinative skills whereas the combinations of diazepam and alcohol did so. To further elucidate the subacute effects, a double-blind randomized study was conducted administering 2 and 10 mg of diazepam t.i.d. for two weeks to 18 healthy volunteers. The psychomotor tests were performed on the 7th and 14th days of drug administration, and 0.5 g/kg of alcohol was given on either day. Diazepam 2 mg, alone or with alcohol, did not differ from placebo. 10 mg of diazepam slightly increased reaction times but not reaction mistakes, and impaired both co-ordination and attention. Alcohol did not enhance diazepam effects. We suggest that a development of tolerance to diazepam may compensate the deleterious interaction of the agents found in acute studies.     

Acute and subacute effects of diazepam on psychomotor skills: interaction with alcohol.

Effects of diazepam and alcohol on psychomotor skills were measured in two trials. In the first one, 200 healthy students volunteered for a double-blind single-dose study. Three doses of diazepam (5, 10 and 20 mg) and alcohol (0.5, 0.8 and 1.2 g/kg) were used alone and combined to construct dose-response graphs. All doses of alcohol impaired divided attention while co-ordinative skills were impaired by the 1.2 g/kg dose. Diazepam alone did not impair reactive or co-ordinative skills whereas the combinations of diazepam and alcohol did so. To further elucidate the subactue effects, a double-blind randomized study was conducted administering 2 and 10 mg of diazepam t.i.d. for two weeks to 18 healthy volunteers. The psychomotor tests were performed on the 7th and 14th days of drug administration, and 0.5 g/kg of alcohol was given on either day. Diazepam 2 mg, alone or with alcohol, did not differ from placebo. 10 mg of diazepam slightly increased reaction times but not reaction mistakes, and impaired both co-ordination and attention. Alcohol did not enhance diazepam effects. We suggest that a development of tolerance to diazepam may compensate the deleterious interaction of the agents found in acute studies.     

A Liquid Chromatographic Assay for 5-Hydroxytryptophan,Serotonin and 5-Hydroxyindoleacetic Acid in Human Body Fluids

Abstract: We describe the precision and accuracy of a liquid chromatographic method, which uses internal standards, 6-fluoroserotonin and 5-hydroxyindolecarboxylic acid, in quantitating serotonin and 5-hydroxyindoleacetic acid in human cerebrospinal fluid, plasma and urine. In addition, 5-hydroxytryptophan is measured in the cerebrospinal fluid. The limit of sensitivity of this method is 0.1 pmol/injection, the peak height/concentration ratio is linear in the concentration range of 0.1 pmol to 50 μmol/injection, and the coefficient of variation is of the order of 15% at the limit of sensitivity and below 10% at amounts above 0.5 pmol/injection. No endogenous monoamines or their metabolites interfere with the quantitation of the substances of interest in the body fluids studied.     

Alcohol intoxication reduces visual sustained attention

Effects of alcohol intoxication on visual sustained attention were studied using a vigilance task entailing detection of degraded target stimuli. Data were obtained in separate sessions under four ethanol doses, ranging from 0 (placebo) to 1.05 g/kg lean body weight, with periodic maintenance dosing of 0.12 g/kg. Intoxication lowered the overall level of detection performance, and in addition produced dose-related increases in the rate of performance decrement over time. Analysis of performance data using techniques derived from Signal Detection Theory indicated that the decrements were due specifically to alterations in perceptual sensitivity. Examination of eye movements and blinks indicated that the effects of ethanol were not mediated peripherally. Rather, alcohol appears to have deleterious effects on central processing capacity and the availability of capacity over time. The alcohol-related failure of sustained attention may contribute to increased accident risk in tasks requiring continuous performance.     

Effects of ethanol on drug and metabolite pharmacokinetics

Pharmacokinetic interactions of ethanol with other drugs, including its effects upon drug metabolite disposition, are reviewed in terms of clearance concepts. This approach is particularly useful in understanding the mechanisms of ethanol-drug interactions, i.e. in separating the effects of ethanol upon drug clearance, volume of distribution and plasma protein binding. The application of clearance concepts provides the basis for understanding the qualitative differences in ethanol interactions with low and high hepatic extraction ratio drugs. The effects of short and long term ethanol consumption upon different types of drug metabolism (oxidative, acetylation and glucuronidation) have been considered. Long term ethanol consumption may increase the clearance of a drug by induction of oxidative metabolism whereas short term consumption may decrease the clearance of such a drug. Clearance by N-acetylation appears to be increased in the presence of ethanol, and clearance by conjugation to glucuronic acid is decreased for some drugs by single-dose consumption of ethanol.     

激素依赖性皮炎的研究进展

由于糖皮质激素外用制剂的不规范应用和误用含激素的化妆品,激素依赖性皮炎的发病率逐年增高。我们复习有关文献,对糖皮质激素依赖性皮炎的病因、发病机制、临床表现、诊断、组织病理及治疗作一综述。     

Neuroendocrine carcinoma of skin with simultaneous cytokeratin expression

An unusual tumor of the skin was removed from the thigh of a 52-year-old white male. By light microscopy, the tumor was composed of intermediate and small cells in sheets and clusters. Ultrastructural study of the tumor cells showed numerous dense core granules and dendritic cell processes as well as intermediate filaments and cell junctions frequently within the same cells. Most of the tumor cells were stained intensely by antibodies to neurone-specific enolase (NSE), a marker of cells of the central and peripheral nervous system. The neuropeptides met-enkephalin and vasoactive intestinal peptide (VIP) were also found in tumor cells. Immunohistochemistry furthermore demonstrated cytokeratin. Both the ultrastructural appearance and keratin content of this tumor set it apart from conventional Merkel cell (or trabecular) carcinoma of the skin in a manner analogous to bipartite (i.e., epidermoid and small cell) carcinoma of lung. The production of neuropeptides simultaneously with the production of keratin establishes this as a bipartite skin tumor (i.e., ectodermal and neuroectodermal phenotype). We suggest that at least some primary neuroendocrine tumors of the skin arise from multipotential ectodermal cells not of neural crest origin, as has been proposed for small cell carcinoma of lung.