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Biomedical subjects

R B Forney

Publications and source records attributed to R B Forney.

At least 37 records · Page 2Linked to original sources

Monitoring phenytoin in salivary and plasma ultrafiltrates of pediatric patients.

The plasma binding of phenytoin and the relationship between phenytoin concentrations in salivary and plasma ultrafiltrates were evaluated in pediatric epileptic patients aged 2-15 years. Paired samples of plasma and saliva were ultrafiltered through an Amicon YMT membrane. Phenytoin concentrations were measured by a gas-liquid chromatography procedure. The phenytoin free fraction among pediatric epilepsy patients not taking valproic acid was normally distributed with a mean (+/- SD) of 9.2 +/- 1.8%. The mean (+/- SD) free phenytoin fraction among patients also taking valproic acid was 13.2 +/- 4.5%. Salivary ultrafiltrates exhibited a close correspondence with plasma ultrafiltrate concentrations, and the ratio of salivary to plasma ultrafiltrate concentrations was 1.06 +/- 0.15. Substantial intraindividual variation in the phenytoin free fraction and the increase in free fraction among patients on valproic acid emphasize the importance of using plasma unbound levels for monitoring phenytoin. The close agreement between plasma and salivary ultrafiltrate concentrations suggests that the latter will provide a practical noninvasive means of monitoring phenytoin.

Adolescent↗

Warfarin binding to plasma of workers exposed to toluene diisocyanate.

The extent of [14]C-warfarin binding to plasma proteins was evaluated in a group of normal, healthy volunteers and in two groups of individuals occupationally exposed to toluene diisocyanate (TDI). Plasma binding was assessed by ultrafiltration after the addition of racemic [14]C-warfarin to a final concentration of 0.8 microgram/ml. Chronic occupational exposure to TDI did not affect the extent of warfarin binding since warfarin free fractions (normalized to an albumin concentration of 4.5 g/dl) were 1.09 +/- 0.23 (mean +/- SD), 0.98 +/- 0.19, and 0.97 +/- 0.15 for controls and the two groups of TDI-exposed individuals, respectively.

Adult↗

Delta-9-tetrahydrocannabinol on isolated human bronchioles.

Experiments were conducted to investigate the bronchodilating action of delta-9-tetrahydrocannabinol (THC) using normal human lung tissue obtained post mortem. Isolated rings of human bronchioles contracted to histamine, carbachol, and prostaglandin F(2a)(PGF(2a)) and relaxed to isoproterenol. THC (5 X 10(-4)M) did not alter the responses of the bronchial rings to histamine, whereas methapyrilene (10(-6)M) antagonized these responses. Atropine (2 X 10(-6)M) had a highly significant effect on the responses of the bronchioles to carbachol: there was also a significant effect of THC (5 X 10(-4)M), but to a much lesser extent than atropine. Propranolol (10(-6)M) pretreatment significantly antagonized the relaxant responses of the bronchioles to isoproternol: THC antagonized these responses to a smaller degree. Incubation with THC did not cause relaxation of resting tissues or tissues in which a spasm had been induced. These data suggest that THC does not have significant direct effects in human bronchial smooth muscle and that bronchoactivity observed in vivo is likely to be of a nondirect or central origin.

Adolescent↗

The effect of time of death on extravascular tissue/blood secobarbital concentration ratios in the rat.

Extravascular liver/blood and brain/blood ratios were found to be an average of 6% and 1% higher, respectively, in all experiments than total liver/blood and brain/blood ratios. This difference may be informative in establishing true tissue levels. There was a significant time effect (P less than 0.05) with the extravascular liver/blood ratios but not with the extravscular brain/blood ratios. Extravascular liver/blood ratios were slightly higher in phenobarbital-pretreated animals than in non-pretreated animals. Tissue secobarbital levels in pretreated and non-pretreated animals are not different at 1/4 or 1 h, even though pretreated animals received higher doses than non-pretreated animals. Tissue levels are significantly higher (P less than 0.01) in pretreated animals than in non-pretreated animals at 4 h. It is possible that, at this time period, the barbiturate-metabolizing enzymes have become saturated or exhausted.

Animals↗

Combined effects of fenmetozole and ethanol.

Eight male subjects took none or 200 mg fenmetozole 1 hr before drinking a beverage containing none or 50 ml/70 kg ethanol. Tests designed to measure mental and motor performance were administered 2 hr after fenmetozole ingestion. Fenmetozole alone impaired standing steadiness but improved mental performance in one test. Fenmetozole did not antagonize the decrement in performance induced by this amount of ethanol. In combination, the subjective symptoms caused by fenmetozole were additive with those of ethanol.

Adult↗

Subjective responses and excretion patterns of dextroamphetamine after the administration of therapeutic doses.

Twelve male medical and graduate students received dextroamphetamine sulfate in doses of 0, 5, 10, and 15 mg/70 kg body weight. The study was conducted in a double-blind manner, and treatments were assigned according to randomized, complete block design. The drug was given orally and subjects were instructed not to eat 3 1/2 h prior to administration. After administration, total urine output was collected for 12 h; no attempt was made to control urinary pH to more realistically approach the general clinical usage of amphetamines. The urine was pooled into two 6-h segments and analyzed for amphetamine concentration. Subjective impressions of the treatments were also evaluated by means of the Cornell Medical Index Questionnaire. Results showed that approximately 30% of the total dose was excreted unchanged within 12 h after administration. The amount excreted agreed very closely with the doses given and paralleled the scores for subjective impressions by the subjects. None of the subjects felt that their driving would be impaired for any of the doses administered. This study indicates that under ordinary conditions (in which pH is not artificially controlled), therapeutic doses of dextroamphetamine can be detected in urine for up to 12 h after oral administration.

Administration, Oral↗

Stimulant actions of delta9-tetrahydrocannabinol in mice.

delta9-Tetrahydrocannabinol (THC) augments the locomotor activity produced by methamphetamine (0.5 mg/kg) in aggregated mice. THC-induced augmentation was dose related and lasted for a two-hour period. Maximal effective dosage of THC was 15 mg/kg with higer dosages of 30 and 60 mg/kg producing a decrease from maximum in locomotor activity. THC, 15 mg/kg, also increases locomotor activity among aggregated animals treated with saline. However, the increase was much less than the methamphetamine augmentation. In similar studies using isolated mice THC produced only a dose-related decrease in locomtor activity among both methamphetamine-treated and saline-treated animals. THC, 60 mg/kg, had no effect on methamphetamine-induced lethality in aggregated mice. However, at 15 mg/kg, THC significantly enhanced the lethality of methamphetamine. THC did not alter methamphetamine lethality in isolated mice. Distribution studies using 14C-methamphetamine indicated that neither THC nor isolation of animals affected tissue concentration or disappearance of 14C material. Previously reported synergistic interaction between amphetamine and THC is related to aggregation of the animals rather than drug treatment. Since THC at low doses can stimulate motor activity in saline-treated animals, amphetamine may act only to amplify the behavioral activity produced by low doses of THC.

Animals↗

Influence of cannabidiol on delta-9-tetrahydrocannabinol effects.

Experiments investigating the possible interaction of tetrahydrocannabinol (THC) and cannabidiol (CBD), two major components of marihuana, were conducted under controlled laboratory conditions in a double-blind manner. In one study, 15 male volunteers were given placebo or 25 mug/kg of THC together with either placebo or 150 mug/kg of CBD by inhalation of the smoke of a single cigarette. All four treatments were assigned to each subject according to a series of Latin-square designs. CBD significantly attenuated the subjective euphoria of THC. Psychomotor impairment due to THC was not significantly altered by the simultaneous administration of CBD, but a trend indicating a decrease in THC-like effects was observed after the combination. When administered alone CBD was inactive for all the parameters measured. In a second study, 8 male subjects were given CBD (0 or 150 mug/kg) by smoke inhalation 30 min before THC (0 or 25 mug/kg) in a second cigarette. In contrast to the simultaneous administration of both drugs, CBD pretreatment did not alter the effects of THC on the parameters observed.

Adult↗

Effects of dextroamphetamine on psychomotor skills.

Twelve healthy male volunteers were given 0, 5, 10, 15 mg/70 kg dextroamphetamine orally in a randomized double-blind fashion. Blood pressure increased linearly with dose while heart rate was unchanged. Although selected individual tests of stance stability and motor function improved in a dose-related fashion, a generalized improvement in performance was not found. Delayed Auditory Feedback (DAF) failed to show improvement in mental performance after dextroamphetamine.

Acoustic Stimulation↗