Biomedical subjects
Publications and source records attributed to D Fagan.
Three separate doses of alcohol (0.2, 0.4 and 0.8 g kg-1) were given to eight volunteers and compared with the effects of a placebo. The order of administration was randomized and the study performed double-blind. A battery of psychometric tests sensitive to central nervous system depression was repeatedly performed for 3.5 h. Alcohol, even in the highest dose, had little effect on psychomotor performance.
A preliminary analysis of a study of the bioavailability and pharmacodynamics of chlormethiazole in healthy young and elderly volunteers has been performed. The bioavailability assessed by a stable isotope method and the pharmacodynamic effects assessed by psychometric tests were found not to differ between the two age groups.
The brains of 30 infants who died after at least one real time ultrasound scan were examined after fixation. The ultrasound diagnosis of either periventricular haemorrhage or periventricular leucomalacia was compared with the macroscopic and histological appearances. Each hemisphere was considered separately for both periventricular haemorrhage and periventricular leucomalacia. The accuracy of ultrasound diagnosis for periventricular haemorrhage was 88%, with sensitivity of 91% and specificity of 85%. The accuracy for periventricular leucomalacia was 90%, with sensitivity of 85% and specificity of 93%. Ultrasound was shown to diagnose the entire range of periventricular leucomalacia lesions. Three hemispheres showed the appearance of prolonged flare, and this correlated with extensive spongiosis and microcalcification of the periventricular white matter, although no macroscopic lesion was seen.
The cardiovascular effects of an infusion of chlormethiazole 30-40 ml min-1 were studied in six patients following an extradural injection of 2% lignocaine. There were small but statistically significant decreases in mean arterial pressure and left ventricular ejection time during the infusion. Increases in the pre-ejection period were noted, but there were no significant changes in cardiac output, stroke volume or heart rate. Patient acceptance was high. It is concluded that sedation with an infusion of chlormethiazole, during surgery carried out under extradural anaesthesia, has no clinically adverse cardiovascular effects.
The gene locus known as mtr confers resistance to hydrophobic dyes, detergents, and antibiotics. It has been suggested previously that the host environment is important in the selection of gonococcal strains with this outer membrane phenotype, and thus that strains with mtr gene loci should predominate in environments high in hydrophobic molecules. Furthermore, resistance to hydrophobic molecules has been related to a sevenfold increase in a minor outer membrane protein. To test these suggestions the outer membrane phenotypes of 61 strains of Neisseria gonorrhoeae were identified using 27 rectal isolates from homosexual men and 34 urethral isolates from heterosexual men who were matched for age. The cell envelope phenotype of each strain was identified on the basis of resistance to various hydrophobic compounds. The results were compared with the protein profiles of these strains on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE); no significant correlation was found.
In this double-blind two-period crossover study, ten healthy volunteers received either 200 mg zimelidine each morning for 5 days, or placebo on the same schedule. On day 5 they received 20 mg temazepam 2 h after zimelidine or placebo. A battery of psychometric tests and subjective measurements was carried out on days 4 and 5. Blood samples were collected on day 5 for pharmacokinetic analysis of temazepam. All the measures of psychomotor performance showed the effects of temazepam, as did two of the subjective measures, the "alert/drowsy" and "steady/dizzy" visual analogue scales. No effect of zimelidine alone on performance or subjective state was seen. Zimelidine showed no discernible interaction with the effects of temazepam as assessed by subjective reports, by psychomotor tests, or by pharmacokinetic analysis.
The haemodynamic effects of a 10:1 mixture of trimetaphan and nitroprusside have been studied before and during the course of surgery, in 12 patients placed in 5 degrees reverse Trendelenburg position. Six patients breathed spontaneously and in six the lungs were ventilated artificially. The mixture had a potent hypotensive action that was almost as rapid in onset and recovery as that produced by nitroprusside alone, but the required dose of each drug was decreased considerably. In patients breathing spontaneously, cardiac output remained unchanged on the induction of hypotension, but it decreased significantly in the IPPV group. Heart rate increased, and stroke volume, peripheral resistance and central venous pressure decreased in both groups. The start of surgery was associated with a need to increase the dose of the hypotensive mixture, and with a further increase in heart rate and decrease in stroke volume. Levelling the operating table produced an increase in cardiac output and discontinuation of the mixture resulted in a rapid return of all measurements towards control values.
Six healthy male volunteers took part in this three-period crossover study. In each session, a dose of trial drug -- either placebo, zimelidine 200 mg, or amitriptyline 75 mg -- was given at 09.00 h. Ethanol (50 g) was taken orally at 1200 h. Blood samples were taken for measurement of drug and ethanol concentrations, and body sway and subjective sedation were determined. No differences in the pharmacokinetics of ethanol were seen between the three treatment sessions. Amitriptyline and ethanol showed marked sedative effects, and the results suggest that these two effects may be additive. The combination of amitriptyline and ethanol results in a particularly marked increase in body sway. No sedative nor alerting effect of zimelidine was seen, nor was any interaction between zimelidine and ethanol apparent.
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An adult male lowland gorilla had been treated with diphenylhydantoin for 6 months following several acute convulsive episodes. The gorilla remained clinically normal during that period. Then, for no apparent reason, it refused its usual diet. Physical examination revealed acute inflammatory gingival hyperplasia. Full mouth gingivectomy and antibiotic and analgesic therapy resolved the oral inflammation and the anorexia.
Recent studies in our laboratory demonstrated that fish macrophages produce nitric oxide. To elucidate the mechanisms which regulate nitric oxide production in teleosts, we examined whether macrophage activating factors (MAFs) secreted by mitogen stimulated leukocytes, induced nitric oxide production in a long-term cultured macrophage cell line and in primary cultures of kidney macrophages from the goldfish. The results indicate that both primary and long term cultured goldfish macrophages produce nitric oxide in response to MAF or bacterial lipopolysaccharide (LPS), and co-stimulation with both factors results in a synergistic induction of nitric oxide production. MAF that induced nitric oxide production were present in leukocyte supernatants as early as 24 h after addition of mitogens to cell cultures. The production of MAF was dependent upon the incubation temperature, presence of serum in the culture medium and duration of incubation: maximal MAF activity was detected in 72-96 h supernatants raised in media with serum at 30 degrees C. MAF-induced nitric oxide production by long term cultured macrophages was inhibited by 1000 microM NG-monomethyl-L-arginine or amino-guanidine, indicating an L-arginine-dependent metabolic pathway for the production of the reactive nitrogen intermediates in teleosts. The biochemical events of cytokine induced nitric oxide production by teleost macrophages appear to be similar to those of mammalian macrophages.