Biomedical subjects

J L Lichtor

Publications and source records attributed to J L Lichtor.

At least 37 records · Page 2Linked to original sources

PubMed1993

Subjective, behavioral and physiological responses to intravenous meperidine in healthy volunteers.

Meperidine is a mu opiate agonist that is frequently used to treat pain. We examined in healthy volunteers (N = 10) the effects of intravenous meperidine (0, 0.25, 0.5, and 1.0 mg/kg) on mood and psychomotor performance. A randomized, placebo-controlled, crossover design was used in which subjects were injected with meperidine or saline in a double-blind fashion. Subjects completed several subjective effects questionnaires commonly used in abuse liability testing studies before drug injection and at periodic intervals for up to 5 h after drug injection. Subjects also completed several psychomotor tests. Meperidine produced a constellation of subjective effects in a dose-related fashion, including increases in ratings of "sedated," "coasting or spaced out" and "feel drug effect" ratings. Many of the drug's subjective effects persisted up to 4 or 5 h after administration of the 1.0 mg/kg dose. Drug liking ratings assessed on a visual analog scale were increased after meperidine injection in about half of the subjects (P = 0.09). Eye-hand coordination was affected slightly by meperidine but other indices of psychomotor functioning were unaffected. Miosis increased in a dose-related fashion. Other physiological parameters, such as vital signs, were not affected by meperidine. We conclude that meperidine in healthy volunteers has robust and long-lasting effects on mood, but may have weaker effects on psychomotor performance.

Adult↗

PubMed1993

Reinforcing effects of extended inhalation of a low nitrous oxide concentration in humans.

The reinforcing, subjective, and psychomotor effects of 30 min of inhalation of 20% nitrous oxide were determined in 12 healthy volunteers using a choice paradigm with 100% oxygen as placebo. Nitrous oxide was chosen on only 22% of choice occasions, indicating that, in general, this concentration did not function as a reinforcer. Nitrous oxide produced changes in mood, but had no effect on psychomotor performance. Three out of the 12 subjects chose nitrous oxide on at least two out of the three choice sessions, and during a poststudy debriefing interview, reported pleasant effects of the drug. The other nine subjects reported unpleasant acute effects of the drug (e.g., drowsiness) or residual (postsession) effects of the drug which, they said, influenced their drug choice. The present results are compared to those results obtained in a previous study in which higher concentrations of nitrous oxide (30 and 40%) also produced relatively low choice rates. The apparent lack of reinforcing effects of extended inhalation of nitrous oxide is discussed.

Adult↗

PubMed1993

Effects of 5-hydroxytryptamine3 antagonist, ondansetron, on cigarette smoking, smoke exposure, and mood in humans.

Recent studies in the animal laboratory indicate that 5-hydroxytryptamine3 (5-HT3) antagonists reduce the reinforcing effects of several psychoactive drugs, including nicotine. The purpose of our study was to determine if ondansetron, a selective 5-HT3 antagonist, affected tobacco cigarette consumption in smokers. In the first experiment, a prospective, crossover, placebo-controlled trial was used in which subjects (N = 7) were exposed in an inpatient research unit to 0, 0.15, 0.3, or 0.45 mg/kg ondansetron in three equally divided doses given 4 h apart. In the second experiment, seven different subjects were exposed to the same trial except the dose range was reduced to about 10%: 0, 0.01, 0.02, or 0.04 mg/kg. In each experiment, order of dosing conditions was determined by a Latin square design. Dependent measures included number of cigarettes smoked during the 24-h session, biologic exposure levels (carbon monoxide and plasma nicotine levels), and mood. Number of cigarettes smoked and biologic exposure levels did not differ across drug conditions in either experiment. There were also no effects of ondansetron on mood. From our study results, we conclude that acute administration of ondansetron, at doses appropriate for antiemesis or at markedly lower doses, does not alter tobacco consumption or smoke exposure in humans.

Adult↗

PubMed1993

Reinforcing effects of extended inhalation of nitrous oxide in humans.

The subjective, psychomotor and reinforcing effects of nitrous oxide at subanesthetic doses (30% and 40% in oxygen) were determined in normal healthy volunteers using a choice paradigm. Thirty percent nitrous oxide was chosen no more often than oxygen (41.6% choice rate), indicating that, for most of the subjects tested, extended inhalation of this nitrous oxide concentration was no more reinforcing than oxygen inhalation. Forty percent nitrous oxide was chosen significantly less often than oxygen (22% choice rate), indicating that, for most of the subjects tested, extended inhalation of this nitrous oxide concentration was less reinforcing than oxygen. Nitrous oxide produced robust subjective effects (e.g., increased ratings of 'high,' 'tingling,' and 'dizzy'). Subjects who chose nitrous oxide reported pleasant subjective effects and liked it, while those who chose placebo reported unpleasant subjective effects and disliked it. Both concentrations of nitrous oxide impaired psychomotor performance in all subjects. The lack of reinforcing effects noted in the present study, given nitrous oxide's known abuse potential, is discussed.

Administration, Inhalation↗

PubMed1993

Assessing the behavioral effects and abuse potential of propofol bolus injections in healthy volunteers.

Propofol is a recently introduced intravenous anesthetic agent, commonly administered to surgical patients because it induces anesthesia smoothly (i.e., provides loss of consciousness rapidly and usually with no complications) and is associated with rapid recovery. Propofol has psychoactive effects that could be construed as pleasant, although little abuse liability testing has been done on this agent in humans. Accordingly, we examined various effects of this agent at different subanesthetic doses (0.2-0.6 mg/kg) in order to characterize this drug's abuse potential (for recreational use or potential for diversion). Using a double-blind, randomized, crossover design, healthy normal volunteers (N = 10) were injected intravenously with the drug or with placebo. Before the injection and for up to 1 h afterwards, mood (including drug liking), memory and psychomotor performance were assessed. Propofol impaired memory and psychomotor performance and produced changes in 10 of 20 VAS mood ratings. Although there was variability in self-reported drug liking, some subjects clearly liked the effects of propofol, especially at the two higher doses. At the debriefing interview held after completion of the study, five subjects said if they had to participate in one more session in which they were given a choice between being injected with the highest dose (0.6 mg/kg) or a placebo, they would choose propofol. These preliminary results suggest that this agent may have some potential for abuse/diversion and perhaps stricter accountability procedures should be established for this drug in settings where general anesthesia or conscious sedation procedures are done.

Adult↗

PubMed1993

The interaction between alcohol and the residual effects of thiopental anesthesia.

BACKGROUND: During ambulatory surgery, barbiturates, such as thiopental, may impair psychomotor performance several hours after administration. It was hypothesized that if patients drink alcohol 4 h after thiopental injection, the increase in psychomotor impairment would be greater than that seen after alcohol ingestion alone. METHODS: Twelve healthy men volunteered to participate in a double-blind, placebo-controlled, crossover study with a Latin square design. On each testing day, the subjects received intravenous injections of either 5 mg/kg of 2.5% thiopental or an equal volume of saline for 30 s. Four hours after injection, the subjects consumed a beverage with or without 0.7 g/kg alcohol. Psychomotor performance and mood were assessed at five times: prior to injection, at 1 h and 3 h after injection, and at 1 h and 3 h after consumption of beverage. RESULTS: Both thiopental and alcohol had strong independent effects on the dependent measures in this study. In addition, body sway, one of the nine psychomotor tests used to assess impairment, was greater after thiopental and alcohol than after alcohol alone. Of eleven adjectives used to assess mood, lightheadedness was cited most frequently after a combination of thiopental and alcohol than after each alone. CONCLUSIONS: Based on our tests of performance and mood, an interaction between thiopental and alcohol is evident; in addition, the interaction between both drugs may exert deleterious effects on higher levels of central nervous system integration.

Adult↗

PubMed1993

Propofol at a subanesthetic dose may have abuse potential in healthy volunteers.

We conducted a study in which the rewarding effects of propofol were assessed in humans, using a discrete-trials choice procedure. Normal healthy volunteers (n = 12) were exposed in a blind fashion to acute bolus injections of 0.6 mg/kg of propofol twice and to a similar volume of Intralipid twice. Then, for the next three sessions, subjects chose which drug (identified by a color code) they wished to receive. We defined propofol choosers if individuals chose propofol two or three times, and nonchoosers if they chose propofol once or not at all. By using a chi 2 goodness-of-fit test of a random choice model, the choice distribution differed significantly from a random choice distribution (P < 0.005). Six subjects were choosers: four subjects chose propofol on all three choice occasions and two subjects chose the drug on 2/3 occasions (referred to hereafter as propofol choosers). Six subjects were nonchoosers: five subjects chose Intralipid on all three choice occasions, and one subject chose Intralipid twice (referred to hereafter as propofol nonchoosers). During sampling sessions, propofol choosers reported pleasant acute effects and no unpleasant residual effects, whereas propofol nonchoosers reported either unpleasant acute subjective effects and/or residual effects from propofol. We conclude that 1) propofol may be rewarding (reinforcing) in some individuals without a history of drug abuse, and 2) further abuse liability testing is needed with this drug.

Adult↗

PubMed1992

Subjective and behavioral responses to intravenous fentanyl in healthy volunteers.

Fentanyl is a mu opiate agonist which is occasionally abused by medical personnel who have ready access to the drug. We examined in healthy volunteers (N = 13) the subjective and psychomotor-impairing effects of intravenous fentanyl (0-100 micrograms/70 kg). A randomized, placebo-controlled, crossover design was used in which subjects were injected with 0, 25 (N = 6), 50 and 100 micrograms/70 kg fentanyl in a double-blind fashion. Subjects completed several questionnaires commonly used in abuse liability testing studies before drug injection and at periodic intervals for up to 3 h after drug injection. Subjects also completed several psychomotor tests at these times. Some aspects of psychomotor functioning (e.g., eye-hand coordination) were impaired by fentanyl. Fentanyl produced dose-related increases in ratings of "high" and "sedated," but also tended to produce dysphoria and somatic symptomatology. Most subjects reported liking the effects of the two higher doses of fentanyl for at least a brief time after injection, but they varied widely in their linking ratings across the 3-h post-drug injection period. Despite the transient increases in liking ratings, fentanyl did not increase scores on a widely-used measure of drug-induced euphoria (morphine-benzedrine group scale of the Addiction Research Center Inventory). The present results suggest that some medical personnel who experiment with fentanyl may like it, and thus be at increased risk for abusing the drug in the future.

Adult↗

PubMed1992

Effects of fasting on responses to intravenous fentanyl in healthy volunteers.

The effects of food deprivation on the subjective, psychomotor, and physiological responses to intravenous fentanyl (50 micrograms/70 kg) were studied in 6 healthy male volunteers. A randomized, placebo-controlled, crossover design was used in which subjects were injected with fentanyl or saline after either 2, 12, or 24 hours of fasting. Subjects completed several subjective effects questionnaires as well as psychomotor tasks prior to, and at regular intervals, following the intravenous injection for a 3-hour period. An observer-rated behavioral checklist was completed at regular intervals during the session and several physiological measures (including measurement of pupil size) were recorded. Fentanyl induced opiate-like mood changes, miosis (pupil constriction), and impairment of extraocular muscle control, and 4 of the 6 subjects reported liking the effects; however, fasting had no impact on any of fentanyl's effects. We conclude that food deprivation up to 24 hours does not alter the subjective, psychomotor, or physiological response to the opiate, fentanyl.

Adult↗

PubMed1992

Clinical recovery and psychomotor function after brief anesthesia with propofol or thiopental.

Propofol, the new intravenous anesthetic agent, is generally used in outpatient anesthesia with expectations of fast recovery. We assessed recovery from anesthesia in a double-blind, crossover, controlled manner in 12 healthy volunteers using clinical tests during the first hour and several psychomotor tests 0.5, 1, 3, 5, and 7 h after brief anesthesia with propofol (2.5 mg/kg and 1.0 mg/kg 3 min later) or thiopental (5.0 mg/kg and 2.0 mg/kg 3 min later). Subjects were able to respond to command, sit, and stand steadily significantly faster (P less than 0.05) after propofol (time until standing steadily 33 +/- 7 min; mean +/- SD) when compared to thiopental anesthesia (time until standing steadily 62 +/- 29 min; mean +/- SD). Psychomotor performance remained significantly worse (P less than 0.05 to P less than 0.001) compared to control for 1 h after propofol and for 5 h after thiopental anesthesia. We conclude that the rapid and complete recovery makes propofol a suitable anesthetic for patients undergoing brief ambulatory surgery.

Adult↗

PubMed1992

Subjective and psychomotor effects of subanesthetic doses of propofol in healthy volunteers.

Propofol is increasingly being used in medical and surgical procedures in which conscious sedation of the patient is desired. The mood-altering and psychomotor effects of subanesthetic concentrations of propofol have not been well characterized. Therefore, we examined the effects of intravenous infusions of different subanesthetic doses of propofol on mood and psychomotor/cognitive performance in healthy volunteers (n = 10). A prospective, randomized, placebo-controlled, double-blind, crossover design was used in which subjects first were administered an intravenous loading dose of propofol or placebo (Intralipid) and then were infused over a 20-min period with a given dose of propofol or placebo. Each subject received placebo (Intralipid loading dose and infusion), low-dose propofol (0.08 mg/kg loading dose and 0.5 mg.kg-1.h-1 infusion), moderate-dose propofol (0.16 mg/kg loading dose and 1.0 mg.kg-1.h-1 infusion), and high-dose propofol (0.32 mg/kg loading dose and 2.0 mg.kg-1.h-1 infusion) in four sessions spaced approximately 1 week apart. Propofol induced changes in mood in a dose-related fashion. Some of these mood-altering effects lingered for as long as 30 min after termination of the infusion, but, in general mood had returned to baseline levels 1 h after termination of the infusion. Intralipid induced no changes in mood during the infusion period. Psychomotor functioning was impaired during, and anterograde amnesia was present after, the high-dose propofol infusion. These results suggest that propofol as a sedative has a spectrum of effects that are well-suited for ambulatory surgery (e.g., sedation, amnesia, and rapid and complete recovery).

Adult↗

PubMed1992

Sedation and recovery of psychomotor function after intravenous administration of various doses of midazolam and diazepam.

A placebo-controlled, double-blind, crossover trial in 11 healthy male volunteers compared clinical sedation and psychomotor function after intravenous injection of midazolam (0.05, 0.1, or 0.15 mg/kg), diazepam (0.15 or 0.3 mg/kg), or placebo (saline). The depth of sedation was estimated at 5-10-min intervals during the first hour after injection. A comprehensive battery of psychomotor tests was used to collect objective data of psychomotor performance before drug injection and 1, 3, 5, and 7 h after injection. Midazolam (0.15 mg/kg) produced the highest scores of sedation and most impairment of psychomotor performance. In most tests, the maximal psychomotor effects seen after 0.3 mg/kg of diazepam did not reach those of 0.1 mg/kg of midazolam. Although the strongest psychomotor effects were induced by midazolam, these effects disappeared sooner than those of diazepam. By 5 h after injection, 0.3 mg/kg of diazepam showed the highest scores of psychomotor impairment. The authors conclude that at least four times as much diazepam as midazolam is needed to produce equally severe psychomotor impairment. That the residual effects of midazolam terminate sooner than those of diazepam probably accounts for the occasional underestimation of the potency of midazolam in clinical practice.

Adult↗

PubMed1992

Subjective, behavioral, and physiologic responses to intravenous dezocine in healthy volunteers.

Dezocine is an agonist-antagonist opiate that acts at the mu receptor, and is used for management of pain. Monkeys will readily press a lever to receive an injection of dezocine, and in former opiate addicts dezocine produces positive subjective effects similar to those of morphine. It is not clear, however, what its subjective effects are in people who do not have a history of opiate abuse. To answer this question, a within-subjects design was used in which 10 normal healthy volunteers (six men, four women) were injected with 0, 2.5, 5.0, and 10 mg/70 kg of dezocine in a double-blind fashion. Subjects completed several questionnaires (e.g., Addiction Research Center Inventory) commonly used in abuse liability testing before and at periodic intervals for up to 5 h after drug injection. We also assessed psychomotor performance (e.g., eye-hand coordination) and several physiologic measures (e.g., pupil size, respiration rate) at these times. Dezocine produced increases in ratings of drug liking (P less than 0.001), as well as other subjective effects that might be considered as pleasant ("good mood," "drunken," "coasting," "happy" ratings) (all P less than 0.05). At the same time, the drug had effects (increased dysphoria and sedation) that typically are not reported by addicts. Dezocine produced psychomotor impairment and miosis (constriction of the pupils) in a dose-dependent fashion. The observation that dezocine produces euphoria and increased drug-liking ratings in individuals without histories of drug abuse suggests that hospitals and surgicenters should have strict accountability procedures with this drug.

Adult↗

PubMed1992

Risk of human immunodeficiency virus in surgeons, anesthesiologists, and medical students.

We postulated that three factors determined the occupational risk of infection from the human immunodeficiency virus (HIV) for surgeons, anesthesiologists, and medical students: first, the risk of needlestick exposure per year (range for surgeons 3.8-6.2, weighted average 4.2; range for anesthesiologists 0.86-2.5, weighted average 1.3; range for third-year medical students 0-5, best estimate 5); second, the risk of seroconversion from a needlestick exposure (0.42%-0.50%); and third, prevalence of HIV in the population served (0.32%-23.6%, depending on geographic location). Thus, the calculated range for occupational risk of HIV infection for a surgeon over a 30-yr period (assuming no change in HIV prevalence or benefit from protective measures) was 0.17%-13.9%; for an anesthesiologist, 0.05%-4.50%. The corresponding range of occupational risk for a medical student during the third year was 0.007%-0.59%. The range of risk is large because the variation in prevalence of HIV infection from one area to another is great. The authors validated the methodology first by using an equation, with estimates from the literature for factors in the equation, to calculate the risk of infection for hepatitis B and then by comparing the results with known rates of infection in the prevaccine era. Calculated occupational risk of hepatitis B infection for anesthesiologists was in the lower range of actual prevalence of infection (calculated range 2.32%-20.6%; known range 6%-26%). Calculated risk versus prevalence for surgeons was fairly close (7.31%-53.4% versus 24.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesiology↗

PubMed1991

Alcohol after sedation with i.v. midazolam-fentanyl: effects on psychomotor functioning.

Patients who arrive home several hours after outpatient surgery may drink alcohol. The extent to which residual drugs used in outpatient surgery interact with alcohol is not known. The purpose of this study was to determine if two i.v. drugs commonly used together in outpatient surgery, midazolam and fentanyl, have residual effects which would interact with alcohol drunk 4 h after injection. Twelve healthy male volunteers participated in a double-blind, randomized, placebo-controlled and cross-over study. Subjects were studied four times successively with a period of 1 week between trials. On each day of testing, the subjects received randomly, by slow i.v. injection (30 s), either saline followed immediately by saline, or midazolam 0.1 mg kg-1 followed immediately by fentanyl 2 micrograms kg-1. Four hours after the injection, the subjects consumed a beverage which either did or did not contain alcohol 0.7 g kg-1. Before and 1, 3, 5 and 7 h after injection (and before and 1 and 3 h after consumption of beverage), psychomotor performance and mood were assessed. While both the combination midazolam-fentanyl and alcohol had independent effects on the dependent measures in this study, there was no interaction between midazolam-fentanyl and alcohol (no potentiating of effects of alcohol by i.v. sedation). We conclude that the effects of benzodiazepines and opioids that are short-acting and used in outpatient surgery have probably dissipated by the time a patient arrives home, and that effects from alcohol ingested at home will probably not be affected by recent administration of these drugs.

Adult↗

PubMed1991

Liver transplantation in children from living related donors. Surgical techniques and results.

Pediatric liver transplantation with reduced size donor organs (RLT) has evolved into a standard clinical procedure increasing the choices of recipients for their treatment. Nevertheless organ availability remains a major problem. The authors therefore have proposed to study the use of hepatic segments from living related donors (LRT) in a group of 20 children less than 2 years of age or weighing less than 15 kg, in whom standard indications for transplantation existed. Volunteer related donors were selected after medical and psychiatric evaluations, and the suitability of the donor's liver was established by functional and radiologic criteria. A two-stage informed consent process assured appropriate "volunteerism." Nineteen infants received LRT as first grafts and one as a second graft. Seventeen of the recipients are alive 3 to 18 months after LRT. Fifteen of 20 patients are currently at home with the original graft and normal liver function (bilirubin less than 1.5 mg/dl) after a median hospital stay of 27 days (range, 14-93 days). Four patients underwent retransplantation, in all cases due to arterial thrombosis. The overall graft survival for 20 primary LRTs is 75%, with follow-up between 3 and 18 months. A number of technical problems occurred during our initial trial, the most aggravating being vascular thrombosis. Refined approaches to vascular reconstruction should reduce the incidence of thrombosis and improve the rate of survival in future cases. The donor group for the initial 20 LRT procedures comprised 12 mothers, 7 fathers, and 1 grandmother. In addition one father and one uncle, who was an identical twin of the recipient's father, who did not qualify for anatomic reasons, were used in repeat LRT. All donors survived and are now in normal health between 3 and 18 months after LRT, having returned to all activities enjoyed before donation. The median hospital stay was 6 days (range, 5-14). Complications were minimal, and all were limited to the first three procedures, in which a full left hepatectomy was performed. After alteration of the procedure into a left lateral segmentectomy, no complications were encountered. The left lateral segmentectomy presents minimal surgical trauma to the liver and should remain the primary approach for obtaining a liver graft from a living donor. For children, transplantation of a left lateral segment from a live donor provides a new way of providing a transplant of appropriate size and with good function. The success of this program has led to the acceptance of LRT for general clinical application in the authors' institution.

Adult↗

PubMed1991

Alcohol after midazolam sedation: does it really matter?

Patients who arrive home several hours after ambulatory surgery may drink alcohol. The extent to which the residual effects of drugs used in ambulatory surgery interact with alcohol, perhaps potentiating alcohol effects, is not known. Accordingly, the purpose of this study was to determine whether intravenous midazolam had residual effects that would interact with alcohol consumed 4 h after the midazolam injection. Healthy male volunteers (n = 16) participated in a double-blind, randomized, placebo-controlled crossover trial. Subjects were studied four times successively with 1 wk between trials. On each test day the subjects randomly received by slow intravenous injection (30 s) either saline or 0.1 mg/kg of midazolam. Four hours after injection, the subjects consumed a beverage that either did or did not contain 0.7 g/kg of alcohol. Before and 1, 3, 5, and 7 h after injection (and before and 1 and 3 h after beverage consumption), psychomotor performance and mood were assessed. Whereas both midazolam and alcohol alone had effects on the dependent measures in this study, there were no significant interactions between the two drugs (i.e., potentiation of alcohol effects by midazolam or potentiation of midazolam by alcohol). We conclude that the effects of a short-acting benzodiazepine used in ambulatory surgery have probably dissipated by the time a patient arrives home, and that effects from alcohol ingested at home will probably not be influenced by the recent administration of a short-acting benzodiazepine such as midazolam.

Adult↗

PubMed1991

Ventricular dysfunction does occur during liver transplantation.

Ventricular dysfunction, then, does indeed occur during liver transplantation, particularly at the time of reperfusion. Pulmonary embolism contributes to right ventricular and right atrial encroachment on left-heart filling, and paradoxical embolism may occur. Pericardial effusions, tricuspid regurgitation, hypothermia, and the release of substances, particularly potassium from the donor liver, may further contribute to compromises in ventricular function. Proper monitoring and appropriate treatment, however, lead to successful operative outcomes in most cases.

Heart Arrest↗