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R I Block

Publications and source records attributed to R I Block.

At least 37 records · Page 2Linked to original sources

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↗

Acute effects of marijuana on cognition: relationships to chronic effects and smoking techniques.

A double-blind, placebo-controlled study assessed acute effects on human cognition of marijuana smoking involving long or short durations of inhalation and breath holding. During eight test sessions, 48 adult, male volunteers completed standardized, pencil-and-paper tests of educational development and ability, as well as computerized tests of learning, associative processes, abstraction, and psychomotor performance. Marijuana impaired all capabilities except abstraction and vocabulary. These impairments were more pervasive than those associated with heavy, chronic marijuana use in a previous study involving the same tests, but showed some similarities. Marijuana altered associative processes, encouraging more uncommon associations. Marijuana-induced impairment in learning pairs of words was influenced by associative relationships between the words. There were a few hints that prolonged breath holding increased marijuana's effects under some test conditions, but in general it did not. Prolonged breath holding itself affected performance in four tests, regardless of whether subjects smoked marijuana or placebo. Whether physiological or psychological factors (e.g., exposure to carbon monoxide in smoke or subjects' expectations) produced these effects could not be determined.

Adult↗

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↗

Effects of chronic marijuana use on testosterone, luteinizing hormone, follicle stimulating hormone, prolactin and cortisol in men and women.

To investigate possible effects of chronic marijuana use on reproductive and stress hormones, we assayed testosterone, luteinizing hormone, follicle stimulating hormone, prolactin, and cortisol in 93 men and 56 women with a mean (+/- S.E.) age of 23.5 +/- 0.4 years. Hormone values were compared among groups of subjects stratified according to frequency of marijuana use (frequent, moderate and infrequent; N = 27, 18, and 30, respectively) and non-using controls (N = 74). Chronic marijuana use showed no significant effect on hormone concentrations in either men or women.

Adolescent↗

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↗

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↗

Effects of a subanesthetic concentration of nitrous oxide on establishment, elicitation, and semantic and phonemic generalization of classically conditioned skin conductance responses.

Classical conditioning of skin conductance responses was studied in 16 men and 16 women breathing 30% nitrous oxide or 100% oxygen to see how nitrous oxide affected establishment, elicitation, and generalization of conditioned responses (CRs). For CRs that had been established before gas inhalation, nitrous oxide blocked elicitation of "anticipatory" (long latency) but not "orienting" (short latency) CRs. Nitrous oxide appeared to prevent new CRs from being established during its inhalation, but learning evidently took place since anticipatory CRs could be elicited after nitrous oxide inhalation had ceased. Words were used as the conditioned stimuli and nitrous oxide altered generalization of CRs to other words related in meaning or sound, though generalization effects were limited. Nitrous oxide also seemed to reduce the efficacy of the unconditioned stimulus. The results were interpreted in terms of Rescorla's theory of classical conditioning.

Adult↗

Marijuana effects on the speed of memory retrieval in the letter-matching task.

Marijuana's effect on the speed of retrieving simple information from memory was studied using a task in which subjects saw two letters and decided whether or not they had the same name. Subjects smoked a single marijuana or placebo cigarette under double-blind conditions. Marijuana slowed reaction time relative to placebo, but this effect was not influenced by the demands on memory retrieval or by providing advance information relevant to the required decisions, suggesting that memory retrieval was unimpaired.

Adult↗

Marijuana effects on associative processes.

Acute marijuana effects on associative processes involved in long-term memory retrieval were studied. Results were partially consistent with expectations based on previous subjective reports that marijuana promotes more uncommon associations. Marijuana altered responses when people gave as many examples of a specified category (e.g., CLOTHING) as they could for 2 min, and when they gave an example of a specified category beginning with a specified letter (e.g., WEAPON - G). Reaction time in the latter task and in prior studies was not altered in the expected manner, a finding problematic for some theoretic interpretations of marijuana's effects on associative processes.

Adult↗