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Biomedical subjects

S A McDonald

Publications and source records attributed to S A McDonald.

13 recordsLinked to original sources

Interaction between ethanol and dextroamphetamine: effects on psychomotor performance.

The objective of this study was to investigate the interaction between ethanol and dextroamphetamine with regard to psychomotor performance. Twelve healthy, male, paid volunteers, moderate users of ethanol and amphetamines, participated in this study. Ethanol (0.85 g/kg or placebo) was administered over a 30-min interval. Five minutes before the termination of ethanol or placebo ingestion, dextroamphetamine elixir (0.09 mg/kg, 0.18 mg/kg or placebo) diluted in 50 ml of orange juice was administered. Subjects were tested in a single-blind, latin-square, crossover design with each of the following six conditions: placebo ethanol/placebo dextroamphetamine; placebo ethanol/low-dose dextroamphetamine; placebo ethanol/high-dose dextroamphetamine; ethanol/placebo dextroamphetamine; ethanol/low-dose dextroamphetamine; and ethanol/high-dose dextroamphetamine. The variables measured in this study were: subjective rating of ethanol and dextroamphetamine intoxication, accuracy and latency of response in the Simulator Evaluation of Drug Impairment (SEDI task), blood ethanol concentration by breath analyzer, and plasma concentrations of dextroamphetamine by gas chromatography. Results indicate ethanol induced decrements in performance of the skills necessary to drive an automobile were significantly decreased by dextroamphetamine in a dose-response fashion. The administration of dextroamphetamine did not decrease the subjective ratings of ethanol intoxication.

Adult

Clinical effects of methamphetamine vapor inhalation.

Despite the increasing popularity of crystalline methamphetamine ("ice") vapor inhalation, no investigations have reported drug plasma concentrations and effects. Under controlled laboratory conditions, six subjects were studied. Plasma concentrations of methamphetamine were determined, and subjective and cardiovascular effects were measured. Methamphetamine appeared in plasma rapidly, increased slowly over the next four hours and then progressively declined. The dose of methamphetamine administered produced modest ratings of subjective drug effects, and moderate changes in cardiovascular parameters. Both subjective and cardiovascular effects rapidly decreased despite the presence of sustained concentrations of methamphetamine in plasma.

Administration, Inhalation

Antagonism of marihuana effects by indomethacin in humans.

To investigate whether the nonsteroidal anti-inflammatory drug (NSAID) indomethacin antagonized the effects of marihuana, an exploratory single-blind, placebo-controlled study was conducted. Subjects (n = 4) smoked marihuana after pre-treatment with placebo and indomethacin. The subjective rating of marihuana "high", heart rate, word recall, time estimation/production, and plasma concentrations of THC and PGE2 were measured. It was found that: 1) indomethacin pre-treatment decreased the elevation of prostaglandins induced by THC; 2) indomethacin significantly attenuated the subjective "high" and the heart rate accelerating effects of THC, although the magnitude of this effect was modest; 3) indomethacin abolished the profound effect of THC on time estimation and production; and 4) indomethacin pretreatment did not affect the decremental effects of THC on word recall. We conclude that prostaglandins are involved in the neurophysiologic mechanisms that mediate some of the typical clinical effects of THC, particularly the distortion of time perception.

Adult

The pharmacologic effects of daily marijuana smoking in humans.

Six healthy male, paid volunteers smoked one NIDA cigarette containing 1.0% THC each day for 13 consecutive days. They were tested before and after the period of drug administration by the following procedure: the subjects smoked one NIDA marijuana cigarette containing 1.0% THC followed 15 minutes later by the intravenous infusion of 52 micrograms/min of deuterated THC for 50 minutes. The THC plasma concentrations, ratings of "high" and heart rate effects produced by the combined drug administration were measured, and absolute bioavailability of smoked THC was calculated on Days 1 and 22. Statistical analyses indicate that the only significant changes induced by daily marijuana exposure were in cardioacceleration.

Adult

Clinical effects of daily methamphetamine administration.

This study investigated alterations in the disposition and pharmacodynamics of methamphetamine HCl after daily administration. Six male paid volunteers familiar with the use of amphetamines participated. Each subject was administered 10 mg of methamphetamine HCl as a slow-release preparation (Desoxyn Gradumets) at 9 a.m. for 13 consecutive days (days 2-14 of the study). On days 1 and 15 the subjects were challenged with 10 mg of oral deuterated methamphetamine HCl. Deuterated drug was used to differentiate plasma concentrations of challenge doses from those of daily doses. The heart rate, subjective perception of "high," and plasma concentrations of methamphetamine were examined on days 1 and 15. Repeated ANOVA measures indicate that a significant decrease in heart-rate acceleration in response to methamphetamine challenge occurred on day 15 [F(1,5) = 8.26, p less than or equal to 0.035]. However, no significant change in either the subjective ratings of "high" or the plasma concentrations of deuterated methamphetamine occurred. These findings indicate that the disposition of methamphetamine and its subjective effects were not altered by this period of daily exposure to a low dose of the drug. In contrast, tolerance to the heart-rate accelerating effect was observed.

Adult

Unsuspected dilution of glutaraldehyde in an automatic washer for flexible fibreoptic endoscopes.

It has been suggested that serial usage of automatic endoscope washer-disinfectors may result in dilution of glutaraldehyde (used as the disinfectant in these machines). However, there are no published data available to confirm this possibility. The authors therefore undertook a study to determine the extent of glutaraldehyde dilution occurring during repeated cycles of an endoscope washer-disinfector over a 14 day period. It was found that the concentration of glutaraldehyde in the endoscope washer-disinfector consistently fell with increasing numbers of wash cycles, and that after 60 cycles the concentration of glutaraldehyde fell below the recommended minimum effective concentration of 1%. Users of automatic endoscope washer-disinfectors should be aware of the potential for dilution of glutaraldehyde in these machines. It is the number of washer-disinfector cycles, and not only the elapsed time since activation of the glutaraldehyde, which determines the frequency with which the glutaraldehyde solution must be replenished. Test kits are now available to measure glutaraldehyde concentration chemically, and may be useful in a quality control program of serial testing of glutaraldehyde concentrations in the endoscope washer-disinfector.

Disinfection

Developmental expression of genes in chick growth cartilage detected by in situ hybridization.

We have used in situ hybridization to examine expression of collagen type I, II, and X mRNA and osteonectin mRNA in the chick epiphysis. Tissue samples from the proximal tibial growth cartilage were fixed in modified Carnoy's solution, dehydrated in ethanol, and embedded in paraffin. Longitudinal and transverse sections were demineralized with HCl and digested with hyaluronidase and proteinase K. In situ hybridization was carried out using biotinylated cDNA probes; the hybridized probe was detected using a streptavidin-biotinylated alkaline phosphatase conjugate. This procedure permitted detection of the corresponding mRNAs in cartilage with high sensitivity and low background. Osteonectin mRNA was detected in proliferating cartilage; lower levels of osteonectin mRNA were seen in the mid-hypertrophic region. This mRNA species was also expressed in cells that border the vascular canals in the premineralized region of the epiphysis. Collagen type X mRNA was detected throughout the hypertrophic zone. As localization of collagen type X mRNA corresponded to the site of maximal synthesis of the protein, reported in other studies, our results would further support the suggestion that this protein is associated with mineralization of cartilage. Collagen type II mRNA was seen in both the proliferating and the hypertrophic regions of the cartilage. Highest levels of expression were observed in the proliferative region. The results suggest that the transcriptional control of collagen type II and X by cells of the proliferating and hypertrophic regions of the growth cartilage may be related.

Animals

Expression of collagen type transcripts in chick embryonic bone detected by in situ cDNA-mRNA hybridization.

The development of the chick embryonic calvarium, an intramembranous bone, is characterized by direct differentiation of cranial ectomesenchymal cells into osteoblasts without the formation of a cartilage anlage. Collagen biosynthesis remains predominantly as type I in the calvaria. However, in severely calcium-deficient chick embryos maintained in shell-less (SL) culture, cartilage-specific type II collagen is synthesized by the calvaria. Immunohistochemistry localized the cells expressing type II collagen to undermineralized regions of the SL bone. In this study, collagen gene expression in bones of normal (N) and calcium-deficient SL chick embryos was examined at Incubation Day 14 by in situ cDNA-mRNA hybridization. A critical step in the procedure, which used biotinylated cDNA probes, was the selection of fixation conditions which maximized RNA retention and maintenance of tissue morphology. Tissues fixed in modified Carnoy's fixative (58% ethanol, 30% choloroform, 10% acetic acid, 2% formaldehyde) for 2-4 hr at -20 degrees C sectioned well and retained their cell morphology and cytoplasmic RNA. Other treatments important for the procedure included demineralization in 0.25 M HCl and removal of matrix by hyaluronidase digestion. In situ hybridization with type-specific collagen cDNA probes revealed that type II collagen mRNA was present in cells throughout the SL calvaria. More importantly, cells with type II collagen mRNA were also present in N calvaria which do not synthesize the protein. The overall abundance of type II-positive cells in N calvaria was not significantly different from that in SL calvaria, but their distribution throughout the bones differed. In general, the regional distribution of type II cells was inversely correlated with the extent of matrix mineralization. In the N calvaria, cells containing collagen type II mRNA were absent in the extensively mineralized superior zone, but were found in the temporal zone which showed limited mineralization. On the other hand, in the SL calvaria, which were substantially undermineralized overall, cells with type II mRNA were found throughout the tissue. Interestingly, the overall ratio of type I cells to type II cells was approximately 50% higher in N calvaria. These findings suggest that collagen type mRNA expression in the chick embryonic calvarium is correlated with, and perhaps dependent on, the extent of tissue matrix mineralization.

Animals

Cell-cycle regulation of center initiation in Dictyostelium discoideum.

The center-initiating behavior of Dictyostelium discoideum amoebae in various cell-cycle phases was investigated. Small populations of synchronized AX-2 cells were seeded 1 in 1000 into cultures of a nonsignaling mutant (NP160) incapable of initiating centers. The ability of the wild-type AX-2 cells to initiate centers among mutant amoebae displayed cell-cycle regulation. Approximately 50% of a population of S-phase cells initiated centers while only 7.5% of a population of late G2-phase cells resulted in center formation. The timing of center formation also varied with cycle position. Synchronous cultures containing only AX-2 S-phase amoebae (no NP160) displayed the initial signs of aggregation after 4.5 hr of starvation and streaming into the aggregate was complete after 6 hr. In contrast, cultures of late G2-phase amoebae initiated aggregation centers after 5.5 hr of starvation and did not complete streaming until 7.5 hr. In addition, the number of aggregates formed by these synchronous cultures of AX-2 cells also varied with cycle position. In general, these results suggest a cell-cycle modulation of the autonomous signaling responsible for center initiation.

Cell Aggregation

The cell cycle and sorting behaviour in Dictyostelium discoideum.

Synchronized cells of the cellular slime mould Dictyostelium discoideum were prepared by mitotic wash-off. Cell counts and DNA synthesis measurements indicated a high degree of synchrony. Cells from each phase of the cell cycle were fluorescently labelled and mixed with unlabelled asynchronous cells. Cells that were in S-phase and very early G2 at the onset of starvation demonstrated a strong tendency to sort to the tip of the subsequent slugs. With reference to these results and published evidence, we discuss the possible role of cell-cycle-related adhesion differences in cell sorting.

Adhesiveness

The photostress recovery test in the clinical assessment of visual function.

To distinguish optic nerve conduction defects from macular disease in patients with otherwise unexplained loss of central vision we first determined the best visual acuity with correction at distance in unilateral defects. The normal eye was tested first and photostressed for ten seconds by looking at an ordinary penlight held 2 to 3 cm from the eye. The time required to read three letters on three Snellen test lines just larger than the best acuity was used as the end point. In 63 eyes with maculopathy the recovery time was prolonged. Prolonged recovery time was not observed in 20 patients who had optic nerve disease.

Diagnosis, Differential

The lateral cervical.

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Cervical Vertebrae