PubMed Health⌕ Search

Biomedical subjects

E J Cone

Publications and source records attributed to E J Cone.

At least 109 records · Page 6Linked to original sources
PubMed1989

Opiate-induced pupillary effects in humans.

The pupillary effects of several opiates were assessed in human volunteers (N = 6) by means of a newly developed hand-held pupilometer, Pupilscan. Static (diameter) and dynamic (light reflex) responses after morphine, heroin, codeine, oxycodone, oxymorphone and hydrocodone were recorded. The opiates caused dose-related decreases in pupillary size and in the velocity of constriction to a light stimulus. The velocity of redilation after a light stimulus was also decreased. These data indicate that opiates cause systematic changes in dynamic pupillary responses in humans and that measures of these changes may be useful in the quantitative estimation of drug-induced impairment.

Adult↗
PubMed1989

Validity testing of commercial urine cocaine metabolite assays: III. Evaluation of an enzyme-linked immunosorbent assay (ELISA) for detection of cocaine and cocaine metabolite.

A validity assessment study was performed on the Genetic Diagnostic Enzyme Immunoassay test kit, a new enzyme-linked immunosorbent assay (GDC ELISA) for detection of cocaine and cocaine metabolite in urine. A set of 290 urine specimens, comprised of clinical cocaine urines collected from 5 male subjects who had received single doses of intravenous cocaine, drug-free urines spiked with cocaine, cocaine metabolites, cocaine isomers, and other drugs of abuse, were assayed by GDC ELISA. The results were compared with results by gas chromatography/mass spectrometry (GC/MS) assay for benzoylecgonine. Concordance was high between the GDC ELISA assay and GC/MS and with results reported earlier for other commercial assays. Detection times and specificity of the GDC ELISA antibody were most similar to those of the Abuscreen radioimmunoassay for cocaine metabolite. Overall, the assay produced no false negative or false positive results and appeared to be a reliable screening test for detection of cocaine and benzoylecgonine in human urine.

Cocaine↗
PubMed1989

Validity testing of commercial urine cocaine metabolite assays: I. Assay detection times, individual excretion patterns, and kinetics after cocaine administration to humans.

A validity study of eight commercial urine assays for detection of cocaine metabolite was performed on clinical specimens collected from human subjects who received single 20-mg intravenous doses of cocaine hydrochloride. The specimens were collected under controlled conditions and analyzed in random order under blind conditions. Benzoylecgonine concentration in each specimen also was determined by gas chromatography/mass spectrometry (GC/MS). Mean times of detection of the last positive specimen (greater than or equal to 300 ng/mL of benzoylecgonine equivalents) after cocaine administration varied among seven of the commercial tests from 16.9 to 52.9 h in the following ascending order: Toxi-Lab less than TDx = EMIT dau = EMIT st less than Abuscreen less than Coat-A-Count = Double Antibody. In contrast, a commercial spot test (KDI Quik Test) which was evaluated for detection of cocaine metabolite produced both false positives and false negatives for benzoylecgonine and was not considered to be a valid test for detection of cocaine metabolite. Half-lives of excretion of benzoylecgonine among four subjects varied from 5.9 to 7.9 h, and overall recovery of benzoylecgonine varied from 15.0 to 34.3% of the administered dose of cocaine.

Adult↗
PubMed1989

Validity testing of commercial urine cocaine metabolite assays: II. Sensitivity, specificity, accuracy, and confirmation by gas chromatography/mass spectrometry.

A comprehensive validity assessment study was performed on eight commercial urine assays for detection of cocaine use. Sensitivity, specificity, and accuracy of each assay were evaluated by analyzing, in random order and under blind conditions, specimens spiked with known drug concentrations and clinical specimens obtained from human subjects after intravenous cocaine use. Commercial assay results were compared with gas chromatography/mass spectrometry (GC/MS) assay of the same specimens for benzoylecgonine. All of the assays examined were determined to have utility in screening for cocaine use, with the exception of the KDI Quik Test, which was not a reliable test for detection of cocaine use. Major differences in sensitivity, specificity, and confirmation rate by GC/MS were noted among the assays, differences which should be taken into consideration when implementing a urine screening test for cocaine use or interpreting test results involving use of these assays.

Adult↗
PubMed1988

Suspiciousness induced by four-hour intravenous infusions of cocaine. Preliminary findings.

Cocaine hydrochloride was administered to experienced users as an intravenous (IV) loading dose of 40 to 80 mg, followed by four-hour continuous IV infusions of either cocaine or placebo. Rates of cocaine infusion were individualized to maintain steady-state cocaine concentrations for the duration of the infusion. During the infusions, subjects rated themselves on questions that assessed their suspiciousness and paranoia, and nurse-observers took descriptive notes on the subjects' behavior; these notes were later scored on a scale for guarded, suspicious, and paranoid behavior. Nurses observed and rated moderately suspicious behavior when cocaine IV bolus loading doses were followed by cocaine infusions, but not when loading doses were followed by saline solution infusions; subjects did not rate themselves as suspicious during any of the study conditions. Suspiciousness during low-dose cocaine infusions significantly correlated with the amount of cocaine previously administered to the subjects. Suspiciousness during infusions was not related to plasma cocaine concentrations, preadmission drug use, or psychiatric symptoms and history. Cocaine infusions may be a useful tool to pursue the biology of stimulant psychoses.

Adult↗
PubMed1988

Disposition kinetics of nicotine and cotinine enantiomers in rabbits and beagle dogs.

The disposition kinetics of nicotine and cotinine enantiomers was determined in rabbits. The clearance of (R)-nicotine was similar to that of (S)-nicotine, but clearance of (R)-cotinine was twice that of (S)-cotinine. Fractional conversions of both enantiomers of nicotine to cotinine were approximately 50%. These results suggest that in rabbits the biotransformation pathways of cotinine, but not nicotine, are influenced by stereochemistry. The disposition kinetics of nicotine enantiomers in beagle dogs was also studied. In dogs, the clearance of (R)-nicotine was slightly greater than the clearance of (S)-nicotine. Methods for the synthesis of (R)-nicotine and (R)-cotinine of high enantiomeric purity and a gas chromatographic method for determination of nicotine enantiomeric purity are described.

Animals↗
PubMed1988

Clonidine partially blocks the physiologic effects but not the subjective effects produced by smoking marijuana in male human subjects.

Clonidine, an alpha 2-agonist, was studied in three male human subjects in a multi-dose pilot study in combination with smoking marijuana cigarettes. Marijuana alone caused increases in responses on subjective effect questionnaires and increased heart rate. Pretreatment with single oral doses of clonidine three hours prior to marijuana induced no changes in subjective effects prior to smoking marijuana and did not diminish the subjective effects produced by marijuana. Clonidine did substantially reduce but did not abolish the marijuana-induced rise in heart rate. Based on these preliminary data from three subjects, it is concluded that clonidine does not have therapeutic value in the clinical management of active marijuana abuse.

Adrenocorticotropic Hormone↗
PubMed1988

Validity testing of the TDx Cocaine Metabolite Assay with human specimens obtained after intravenous cocaine administration.

Clinical specimens obtained from human subjects after intravenous cocaine administration were analyzed by the TDx Cocaine Metabolite Assay (TDx) and by GC/MS for benzoylecgonine. The TDx results were significantly correlated with results by GC/MS assay with no evidence of bias in the TDx assay. All cocaine metabolite positive specimens (greater than or equal to 300 ng/ml) were confirmed by GC/MS. Detection times to the last positive specimen by TDx assay and GC/MS assay of four subjects after a 20-mg intravenous dose of cocaine ranged from 29.3 to 39.1 h and 27.9 and 36.6 h, respectively. Overall, the TDx assay was found to be highly specific and accurate for the detection and measurement of benzoylecgonine in urine.

Cocaine↗
PubMed1988

Effects of the stereoisomers of nicotine and nornicotine on schedule-controlled responding and physiological parameters of dogs.

The behavioral and physiological effects of five tobacco alkaloids were assessed in two different test paradigms. One group of beagle dogs (N = 5) responded under a multiple fixed-interval (FI) 300 sec, fixed-ratio (FR) 30 response schedule of food presentation. With both l-nicotine (0.1-3.0 mumol/kg i.m.) and l-nornicotine (0.1-10.0 mumol/kg i.m.), FI response rates, when averaged across the entire session, were increased at low doses and decreased at high doses; FR response rates were only decreased. d-Nicotine (0.1-30.0 mumol/kg i.m.), and d- and dl-nornicotine (0.1-10.0 mumol/kg i.m.) produced a transient increase in FI response rates at low doses. The effects of the same five compounds on pupillary diameter, rectal temperature and heart rate were measured in a second group of beagle dogs (N = 6). Both pupillary diameter and rectal temperature were decreased initially by l-nicotine (0.6 mumol/kg i.v.), d-nicotine (6.0 mumol/kg i.v.) and d-, l- and dl-nornicotine (3.0 mumol/kg i.v.); base-line levels were recovered within 60 min. Aside from differences in potency, the time courses of action were similar for all five compounds. Increases in heart rate also were produced by all five compounds, but there were marked differences in the duration of action. l-Nicotine and d- and dl-nornicotine produced appreciable, sustained increases in heart rate, whereas d-nicotine and l-nornicotine produced moderate, brief increases. The combined results of the present experiments indicate the stereoisomers of nicotine and nornicotine are behaviorally and physiologically active, and may contribute in varying amounts to the pharmacologic actions of tobacco.

Animals↗
PubMed1987

Determination of delta 9-tetrahydrocannabinol in human blood and saliva by high-performance liquid chromatography with amperometric detection.

A rapid, sensitive and selective determination of delta 9-tetrahydrocannabinol (THC) in human plasma, serum and saliva was developed with high-performance liquid chromatography with electrochemical detection. Initially, samples were deproteinized, followed by a one step liquid-liquid extraction. Samples were measured by high-performance liquid chromatography with electrochemical detection with 4-dodecylresorcinol as the internal standard. The minimal detectable limit for THC in biological samples was ca. 1 ng/ml with a signal-to-noise ratio greater than 3, corresponding to an on-column sensitivity for THC of ca. 0.5 ng. The detector was operated at + 0.90 V vs. Ag/AgCl and exhibited linearity over a concentration range of 1-150 ng/ml with correlation coefficients of the standard curves greater than 0.99.

Chromatography, High Pressure Liquid↗
PubMed1986

Acute effects of smoking marijuana on hormones, subjective effects and performance in male human subjects.

Four healthy male subjects smoked two marijuana cigarettes or one marijuana cigarette and one placebo cigarette, or two placebo cigarettes on separate days in a random order crossover design. Each marijuana cigarette contained 2.8% delta-9-tetrahydrocannabinol (THC). Plasma hormones and THC were measured before and after each smoking session. Plasma LH was significantly depressed and cortisol was significantly elevated after smoking marijuana. Nonsignificant depressions of prolactin, FSH, testosterone and free testosterone and elevation of GH also occurred. Concurrent measures of subjective effects via subscales of the Addiction Research Center Inventory, Single Dose Questionnaire and a Visual Analog Scale were generally elevated. Significant impairment on a psychomotor performance task paralleled elevations in subjective effects, hormone effects and peak THC determinations. Although all the hormone effects were within normal basal ranges, interactions between these systems, and their effects on behavior cannot be discounted.

Adrenocorticotropic Hormone↗
PubMed1986

Intravenous self-administration of fencamfamine and cocaine by beagle dogs under fixed-ratio and progressive-ratio schedules of reinforcement.

Catheterized beagle dogs were given access to response-contingent intravenous injections of fencamfamine (FEN) or cocaine (COC) injections under a fixed-ratio (FR) schedule of reinforcement. Both drugs maintained self-administration behavior considerably above saline levels; there was an inverted U-shaped relationship between the number of injections per daily session and the dose per injection. Presession treatment with the dopaminergic antagonist pimozide (PIM) appreciably altered both the FEN and COC dose-effect curves, suggesting a dopaminergic component in the reinforcing properties of these substances. When tested under a progressive-ratio (PR) schedule, both FEN and COC maintained nearly identical FR-values which were considerably above those seen for saline. It appears from these data that FEN may have a cocaine-like abuse potential.

Animals↗