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Biomedical subjects

M M Ghoneim

Publications and source records attributed to M M Ghoneim.

At least 55 records · Page 3Linked to original sources

Effects of subanesthetic concentrations of isoflurane and their interactions with epinephrine on acquisition and retention of the rabbit nictitating membrane response.

BACKGROUND: Evidence concerning the concentrations of volatile anesthetics that prevent learning and recall is limited. Epinephrine is believed to enable learning during anesthesia. We investigated the effects of isoflurane and its interaction with epinephrine on learning and subsequent retention of the rabbit's classically conditioned nictitating membrane response. METHODS: In experiment 1, a tone (conditioned stimulus, CS) preceded paraorbital shock (unconditioned stimulus, US) during 60-min daily sessions of 60 presentations of these paired stimuli for 6 days of acquisition training under 0, 0.4%, or 0.8% isoflurane (n = 8, 13, and 9, respectively). Responses were recorded as conditioned responses (CRs) if they occurred during the CS and before the onset of the US. After 1 day of rest, the animals were given 3 days of extinction consisting of 60 presentations of CS-alone and without isoflurane to assess the retention of CRs from acquisition training. In experiment 2, epinephrine in a dose of 0, 0.01, or 0.1 mg/kg was injected subcutaneously in rabbits receiving 0.4% isoflurane. Two types of epinephrine were used, a sustained release form and epinephrine hydrochloride. Acquisition and retention were tested in the same way as in experiment 1. No isoflurane or epinephrine was used during retention testing. RESULTS: Learning was significantly suppressed during 0.4% isoflurane (approximately equal to 0.2 MAC) treatment and eliminated during 0.8% (approximately equal to 0.4 MAC). Information learned during administration of 0.4% isoflurane was not retained (P < 0.05). Although the low doses of epinephrine improved learning during the last day of the acquisition phase (P < 0.05), there were no differences between the treatment groups on any of the remaining acquisition or extinction days. CONCLUSIONS: There was no learning during treatment with 0.8% concentration. Even a 0.4% concentration, which allowed some learning, abolished CRs in extinction, perhaps because of state-dependent retrieval. Epinephrine did not alter substantially the rates of CR acquisition or resistance to extinction.

Animals↗

Effects of chronic marijuana use on human cognition.

Impairments of human cognition and learning following chronic marijuana use are of serious concern, but have not been clearly demonstrated. To determine whether such impairments occurred, this study compared performance of adult marijuana users and non-users (N = 144 and N = 72, respectively) matched on intellectual functioning before the onset of drug use, i.e., on scores from standardized tests administered during the fourth grade of grammar school (Iowa Tests of Basic Skills). Subjects were given the twelfth grade versions of these tests (Iowa Tests of Educational Development) and other, computerized cognitive tests in successive test sessions. "Heavy" marijuana use (defined by use seven or more times weekly) was associated with deficits in mathematical skills and verbal expression in the Iowa Tests of Educational Development and selective impairments in memory retrieval processes in Buschke's Test. The retrieval impairments were restricted to words that were easy to visualize. Impairments depended on the frequency of chronic marijuana use, i.e., "light" and "intermediate" marijuana use (defined by use one to four and five to six times weekly, respectively) were not associated with deficits. Intermediate use was associated with superior performance in one condition ("fuzzy" concepts) of a Concept Formation test.

Adolescent↗

The interactions of midazolam and flumazenil on human memory and cognition.

BACKGROUND: Previous research has been unable to show unequivocally whether flumazenil can reverse completely, partially, or not at all the memory effects of benzodiazepines. The effects of midazolam on implicit memory are also unknown. The behavioral effects of flumazenil by itself, and the acute reversal of benzodiazepine effects, are also controversial. The current study was designed to investigate these questions. METHODS: Using a prospective randomized, double-blind crossover study design, memory was assessed using both direct (free recall and recognition) and indirect (word completion) measures. Other cognitive effects were assessed using the digit symbol substitution task. Sedation and other mood effects were assessed using subjective rating scales. Seventy-two healthy subjects were assigned to three equal groups according to the dose of midazolam received (0, 0.05, and 0.1 mg/kg). Each subject received varying doses of flumazenil (0, 1, and 3 mg) in three sessions, at least 1 week apart. After baseline administration of the tasks, midazolam was administered. The assessments were repeated 20 min later, followed by administration of flumazenil. The assessments were repeated 5 and 30 min after administration of flumazenil. After a 2-h recovery period, delayed memory tests were given. RESULTS: Both doses of midazolam decreased all scores in the memory and digit symbol substitution tests and mood ratings. Flumazenil reversed both the sedative and the memory effects of the benzodiazepine. The reversal was as complete with the 1-mg dose of flumazenil as with the 3-mg dose. Flumazenil by itself, and the acute reversal of midazolam effects, caused no significant behavioral reactions. CONCLUSIONS: Midazolam impairs explicit and implicit memory. Flumazenil reverses both the sedative and memory effects of the drug. Flumazenil, in the doses used, has no intrinsic actions.

Adolescent↗

Sodium pentobarbital: sensory and associative effects in classical conditioning of the rabbit nictitating membrane response.

Four experiments were conducted to determine the effects of sodium pentobarbital (0, 3, 9, and 15 mg/kg) on the acquisition of the rabbit's classically conditioned nictitating membrane response (NMR) and to determine the locus of the drug's effects on sensory, motor, associative, and nonassociative processes. In experiment 1, classical conditioning of the NMR was accomplished by pairing tone and light conditioned stimuli (CSs) with paraorbital shock as the unconditioned stimulus (US). The experiment revealed that pentobarbital retarded the acquisition of conditioned responses (CRs) to both tone and light CSs. Experiment 2, employing unpaired CS, UCS presentations, indicated small but significant drug effects on NMR base rate and nonassociative NMRs to the CS. Experiment 3 revealed no significant drug effect on the psychophysical functions relating UCS intensity to UCR frequency or amplitude, nor on the UCS intensity threshold for eliciting UCRs. On the other hand, in experiment 4, the drug significantly impaired CR frequency over an extended range of CS intensities and raised CS intensity threshold. It was concluded that pentobarbital's attenuation of CS intensity also operated to impair CR acquisition.

Acoustic Stimulation↗

No evidence of classical conditioning of electrodermal responses during anesthesia.

Classical conditioning of skin conductance responses was studied in 26 healthy volunteers and 31 patients who received general anesthesia (0.5 MAC isoflurane-70% nitrous oxide) for minor gynecologic surgery to determine whether there was autonomic evidence of new learning during anesthesia. In the conditioning phase, a loud noise was paired with a target word (conditioned stimulus [CS]). Conditioning was established if the CS produced conditioned responses, i.e., greater skin conductance responses than other, "filler words." In the subsequent elicitation phase, we investigated whether it was possible to elicit similar conditioned responses to the CS when it was presented without noise about 3 h later. Conditioning was established in the control group, who received no anesthesia. There were differences in response magnitudes of 0.32 and 0.27 mu siemen between responses to the CS and filler words, P less than 0.001. In contrast, there was no evidence that conditioning was established during anesthesia. In the elicitation phase, conditioned responses to the CS could be elicited in volunteers; i.e., response magnitudes were greater for the CS than other words (during the first two blocks of trials), with differences of 0.19 to 0.48 mu siemen, P less than 0.05 to P less than 0.001. In contrast, responses to the CS could not be elicited in patients after anesthesia. There was also no evidence of recognition of words that were presented during anesthesia in patients, but recognition was manifested in volunteers. Thus, in contrast to our previous demonstration of conditioning in subjects who received 30% nitrous oxide in oxygen, there was no evidence of conditioning in anesthetized patients.

Adult↗

Human learning during general anaesthesia and surgery.

To determine if learning occurs during general anaesthesia, 72 women undergoing surgery were given postoperative implicit memory tests in which performance could be influenced by auditory information presented during general anaesthesia. Two methods of anaesthesia were used: nitrous oxide and opioids (n = 24) or nitrous oxide and isoflurane (1, 1.3 and 1.5 MAC for n = 12, 24 and 12, respectively). Three tests showed some retention, apparently unconscious, of information presented during anaesthesia: in Behavioural Suggestions tests, patients who were instructed during anaesthesia to touch a particular body part (ear or nose) during later questioning touched the "correct" (suggested) body part longer than the "incorrect" (not suggested) body part during a postoperative interview on the day of surgery (means 2.5 vs 0.2 s); in World Completion tests, patients shown a page containing the first three letters of words and asked to give words beginning with those letters gave more words from a list that had been played during anaesthesia than from a list not played (means 0.48 vs 0.27 words); in Nonsense Word tests, patients who were played different nonsense words between two and 16 times during anaesthesia preferred and guessed more accurately those that had been played most often (16 times) relative to those played less often in subsequent preference and recognition tests (means 56% vs 46% for preference and 62% vs 48% for recognition), while showing no such patterns in additional control tests. Learning did not vary with the method of anaesthesia, as might have been expected if learning was a monotonic function of brain depression. Some information processing functions of the brain evidently continue to function during adequate general anaesthesia.

Adult↗

Efficacy of therapeutic suggestions for improved postoperative recovery presented during general anesthesia.

There have been claims that the postoperative course of patients may be improved by presentation during general anesthesia of therapeutic suggestions which predict a rapid and comfortable postoperative recovery. This study evaluated the effectiveness of such therapeutic suggestions under double-blind and randomized conditions. A tape recording predicting a smooth recovery during a short postoperative stay without pain, nausea, or vomiting was played during anesthesia to about half the patients (N = 109), while the remaining, control patients were played a blank tape instead (N = 100). The patients were primarily undergoing operations on the fallopian tubes, total abdominal hysterectomy, vertical banding gastroplasty, cholecystectomy, and ovarian cystectomy or myomectomy. The anesthesia methods consisted of either isoflurane with 70% nitrous oxide in oxygen to produce end-tidal concentrations of 1.0, 1.3, or 1.5 MAC; or 70% nitrous oxide in oxygen combined with high or low doses of opioids. Assessments of the efficacy of the therapeutic suggestions in the recovery room and throughout the postoperative hospital stay included: the frequency of administration of analgesic and antiemetic drugs; opioid doses; the incidence of fever; nausea, retching, and vomiting; other gastrointestinal and urinary symptoms; ratings of pain; ratings of anxiety; global ratings of the patients' physical and psychological recoveries by the patients and their nurses; and length of postoperative hospital stay. There were no meaningful, significant differences in postoperative recovery of patients receiving therapeutic suggestions and controls. These negative results were not likely to be due to insensitivity of the assessments of recovery, as they showed meaningful interrelations among themselves and numerous differences in recovery following different types of surgery. Widespread utilization of therapeutic suggestions as a routine operating room procedure seems premature in the absence of adequate replication of previously published positive studies.

Adult↗

Appraisal of the quality of assessment of memory in anesthesia and psychopharmacology literature.

To test the hypothesis that there are important differences between studies on memory published in anesthesia literature and those published in the psychopharmacology literature, we compared the two from the period January 1978 through May 1988 to identify deficiencies in the design and methodologies used and to provide guidelines for future experiments. Eight-eight articles in each discipline were reviewed. The sample sizes were larger in the articles in anesthesia journals than in those in psychopharmacology journals (medians 52.5 vs. 18 subjects, respectively). Most (85%) of the studies in the anesthesia literature used patients, who had a median age of 38.9 yr and included a median of 28 women among the subjects per study. In contrast, the majority (60%) of the studies in the psychopharmacology literature used healthy volunteers, who had a median age of 23.6 yr and included a median of only 3.5 females among the subjects per study. Characteristics more common in the psychopharmacology than in the anesthesia literature, respectively, were use of a control or placebo group (90% vs. 42%), double-blind design (80% vs. 47%), use of pre- and posttreatment memory measurements (64% vs. 23%), use of multiple memory tests with distinct equated stimuli (83% vs. 8%), relation of methodology to some theoretical model of memory (72% vs. 17%), and use of other behavioral tests (68% vs. 48%). Relative to the psychopharmacology literature, the anesthesia literature used pictures as stimuli for the memory tests more often (44% vs. 14%, respectively) and words less often (11% vs. 67%) and relied heavily on questions about recall of perioperative events (41% vs. 0%). There is room for improvement in both types of literature, and more so in the anesthesia literature.

Anesthesia↗

Metabolites of methohexitone do not contribute to its prolonged action on the central nervous system.

Methohexitone has been reported to have a prolonged action on the central nervous system (CNS) despite its relatively short elimination half-life. A hydroxy metabolite of methohexitone was identified, purified and isolated from the urine collected from eight surgical patients and five mongrel dogs anaesthetized with methohexitone. Using a rotarod device, the CNS-activity of the human and canine metabolites was tested in mice and compared to that of methohexitone. In this test, the metabolites showed CNS-depressant activity, but the ED50 (dose needed to affect 50% of the animals) of the metabolites was ten times higher than the ED50 of the parent drug. Because in patients, no traces of the hydroxy metabolite could be found in blood, and in dogs the plasma concentration of the metabolite was about two-thirds of that of the parent compound, it is unlikely that the residual CNS-effects of methohexitone are due to its major metabolite, hydroxymethohexitone.

Animals↗

Time course of antagonism of sedative and amnesic effects of diazepam by flumazenil.

Reversal of the sedative and amnesic effects of intravenous diazepam by the benzodiazepine antagonist flumazenil was investigated in 30 patients undergoing conscious sedation for dental surgery. Verbal memory tasks were administered and patients' subjective ratings of mood were obtained before and after diazepam and then periodically after intravenous administration of flumazenil or placebo under double-blind conditions. Immediate and delayed recall and recognition tests showed that diazepam impaired memory and that flumazenil partially reversed this impairment. The subjective ratings showed that diazepam produced physical and mental sedation and that flumazenil reversed this sedation. The reversal produced a return to presurgery scores for mental sedation but not for physical sedation or memory. For physical sedation, the difference between flumazenil and placebo was not demonstrable for more than 15 min after flumazenil administration; for mental sedation, it was demonstrable for as long as 60 min. The reversal by flumazenil of diazepam-induced memory impairment did not change significantly over time.

Adult↗

Norms for free associations and five types of constrained associations.

Normative data on verbal free associations and constrained associations of five types (opposites, superordinates, examples of categories, coordinates, and properties) were collected from 72 men and 72 women (mean age, 19.2 yr.). A list of the different responses given by subjects for each of 360 stimuli and the frequency of each response is available.

Adolescent↗

Effects of a subanesthetic concentration of nitrous oxide on overt and covert assessments of memory and associative processes.

Drug effects on human memory are usually assessed by overt recall or recognition tests. Covert tests which do not explicitly assess memory but which indirectly elicit previously presented information may be more sensitive to low levels of learning than overt tests. Three covert tests and corresponding overt recall tests were given to 16 men and 16 women breathing 30% nitrous oxide in oxygen or 100% oxygen to see if the covert tests resisted the memory-impairing effects of nitrous oxide. Nitrous oxide impaired performance on the overt tests. Performance in two covert tests, Constrained Associations and Word Completion, showed resistance to memory impairment. In the least resistant covert test, Free Associations, nitrous oxide altered associative processes. Performance in an additional test involving recognition and preferences for nonsense words repeated with varying frequencies also showed some resistance to memory impairment. The results support the distinction between declarative and procedural memory. Constrained Associations, Word Completion, and Nonsense Words tests may be useful for assessing low levels of learning during drug states.

Adolescent↗