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Biomedical subjects

J A Thornton

Publications and source records attributed to J A Thornton.

At least 19 recordsLinked to original sources

Testing and analytical procedures for laboratory studies involving nonresponders during a limited observation period: an illustration using male sexual behavior in rats.

In many laboratory studies, a subpopulation of subjects fails to exhibit the response under investigation during the period of observation. For example, within any population of male rats, there is significant variation in the expression of sexual behavior in the presence of a receptive female. Some males may never display the full sequence of behaviors leading to ejaculation within the typical time frame of the testing session, with the resulting lack of behavioral response presenting problems in the analysis of the data. Conventional strategies range from screening such males from the study or dropping them from the analysis to constructing new variables based on estimates from existing parameters or increasing the length of the test session to capture sexual responses in a greater portion of males. Herein, we present an alternative strategy for analyzing data where outcomes are absent due to the limited observation period. Survival regression analysis enables inclusion of all subjects in the analysis whether or not they have shown the behavior of interest. Use of such a strategy not only has potential to reveal new results but also guards against bias from excluding nonresponders from the study or dropping more males from one experimental condition than another. Furthermore, this procedure can be helpful in generating the conditional probability (increase, decrease, or constant) of the response with the passage of time based on the hazard function and in estimating parameters for establishing an optimal behavioral test length for future studies.

Analysis of Variance↗

The influence of associability changes in negative patterning and other discriminations.

Normal rats showed faster learning of a serial negative patterning (NP) discrimination (X+, A+, X-->A-) than of a comparable feature negative (FN) discrimination (A+, X-->A-). This advantage was absent in rats with lesions of the amygdala central nucleus. Earlier data indicated that this brain lesion interferes with surprise-induced increases in attention specified by the Pearce-Hall model (J. M. Pearce & G. Hall, 1980). In the NP task, but not the FN task, omission of the reinforcer after X on X-->A- trials was surprising. A variation of the NP task (NPX), in which X was reinforced on both X+ and X-->A- trials, was learned more rapidly than the NP task. Lesioned rats were unimpaired in learning the NPX task. Evaluation of the lesion effects and the results of posttraining transfer tests suggested that the NP advantage involved attentional processes, whereas the NPX advantage was based on the acquisition of inhibitory control by aspects of excitation conditioned to X.

Animals↗

Selective hippocampal lesions yield nonspatial memory impairments in rhesus monkeys.

Monkeys with removals of medial temporal lobe (MTL) structures are widely recognized as valid models of human global anterograde amnesia, a syndrome that arises consequent to damage to a finite set of brain structures situated in the medial temporal lobe and/or medial diencephalon. However, a comparison of memory deficits in human and nonhuman primates with MTL damage has presented a long-standing puzzle. Whereas amnesic patients are impaired in learning object discrimination problems, monkeys with MTL damage are typically not. One possible explanation for this difference is that object discrimination tasks for humans and monkeys differ in that the former but not the latter requires the use of contextual information. If this analysis is correct, monkeys with MTL damage might be disadvantaged in learning to discriminate similar objects presented in different contexts. To test this possibility, we evaluated the effects of excitotoxic lesions of one of the MTL structures, the hippocampus, on the rate of learning of discrimination problems embedded within unique contexts. Monkeys with hippocampal lesions were impaired relative to controls in learning object discrimination problems of this type. These findings strongly support the idea that the difference in the effect on object memory of MTL damage in human and nonhuman primates is due to a difference in the opportunity to employ contextual cues rather than to a difference in the organization of memory.

Animals↗

Rhinal cortex ablations fail to disrupt reinforcer devaluation effects in rhesus monkeys (Macaca mulatta).

Studies have shown that excitotoxic lesions of the amygdala attenuate reinforcer devaluation effects in monkeys and rats. Because the rhinal (i.e., entorhinal and perirhinal) cortex has prominent reciprocal connections with the amygdala and has been suggested to store knowledge about objects, it is possible that it too composes part of the critical circuitry subserving learning about objects and their associated reinforcement value. To test this possibility, rhesus monkeys with rhinal cortex removals as well as unoperated controls were tested using a reinforcer devaluation procedure. Monkeys with rhinal cortex removals and controls, unlike those with amygdala lesions, tended to avoid displacing objects overlying a devalued food. These results indicate that the rhinal cortex is not a critical part of the neural circuitry mediating the effects of reinforcer devaluation.

Analysis of Variance↗

Rhinal cortex removal produces amnesia for preoperatively learned discrimination problems but fails to disrupt postoperative acquisition and retention in rhesus monkeys.

To test whether the rhinal cortex (i.e., entorhinal and perirhinal cortex) plays a time-limited role in information storage, eight rhesus monkeys were trained to criterion on two sets of 60 object discrimination problems, one set at each of two different time periods separated by 15 weeks. After the monkeys had learned both sets, two groups balanced for preoperative acquisition rates were formed. One group received bilateral ablation of the rhinal cortex (n = 4), and the other was retained as an unoperated control group (n = 4). After a 2 week rest period, monkeys were assessed for retention of the object discrimination problems. Retention was significantly poorer in monkeys with removals of the rhinal cortex relative to the controls (68 vs 91%). Although both groups showed slightly better retention of problems from the more recently learned set, there was no evidence of a differential effect of the cortical removal across sets (i.e., no temporal gradient). In addition, the monkeys with rhinal cortex lesions subsequently learned three new sets of 10 object discrimination problems as quickly as the controls did, thus ruling out the possibility of a gross impairment in visual perception or discrimination abilities. Furthermore, they retained these postoperatively learned object discriminations as well as the controls did. The findings indicate that the rhinal cortex is critical for the storage and/or retrieval of object discrimination problems that were learned up to 16 weeks before rhinal cortex ablation; however, in the absence of the rhinal cortex, efficient learning and retention of new discrimination problems can still occur.

Amnesia, Retrograde↗

Ventilatory effects of isoflurane: a comparison with halothane in a draw-over system.

Halothane and isoflurane were studied using a draw-over anaesthetic system in two groups each of 25 patients to compare the ventilatory effects of the two agents in field anaesthesia. Respiratory variables were measured and it was confirmed that isoflurane is a more potent respiratory depressant than halothane, but satisfactory anaesthesia for short procedures was possible.

Anesthesia, Inhalation↗

A comparison of alfentanil requirements in European and Asian patients during general anaesthesia.

Alfentanil requirements were compared in thirty-six Asian and forty-three European patients during general anaesthesia with muscle relaxants. Alfentanil infusion at 5 micrograms/kg/min was started immediately after induction with thiopentone and alcuronium. The infusion rate was reduced to 0.5 microgram/kg/min after ten minutes. An incremental dose of 5 micrograms/kg/min for five minutes was given on each occasion when anaesthesia was clinically judged to be inadequate. Recovery parameters were recorded. Pharmacokinetics were also studied in five Europeans, four Chinese and four Nepalese. The dosage of alfentanil required was comparable in both Asian and European patients, but recovery was slower in the Asian patients. The elimination half-life in the Chinese and the Nepalese were both significantly shorter than that of the Europeans (P less than 0.05), but at the time of recovery of spontaneous ventilation, the mean plasma concentrations were not significantly different.

Adolescent↗

Midazolam in conservative dentistry. A cross-over trial.

In a double-blind trial, 50 patients were randomly allocated to receive up to 0.29 mg/kg diazepam (Valium 5 mg/ml) or 0.14 mg/kg of midazolam (midazolam hydrochloride 5 mg/ml) intravenously at a first session of conservative dentistry, the alternative being administered at the second session. Good operating conditions were reported under each sedative and no important physiological differences were observed. Most patients failed to return to 'street fitness' 30 minutes after either session of treatment. Previous reports of reduced incidence of venous thrombophlebitis with midazolam were not convincingly confirmed in this trial, but data quality was poor. For about half the patients, the amnesic effect was stronger following midazolam.

Adolescent↗

Assessment of the role of an immunofluorescent terminal deoxynucleotidyl transferase kit.

The laboratory use of a commercial kit for the immunofluorescent measurement of terminal deoxynucleotidyl transferase (BRL Terminal Deoxynucleotidyl Transferase Immunofluorescent Assay System) has been investigated. The precision of the assay system with stored patient material and its performance with regard to ease of microscopic examination were assessed. The intensity of the fluorescence obtained was found to vary. However, the precision of the assay system on fixed slides stored at -30 degrees C was satisfactory; the method simple, and results obtainable in a relatively short space of time.

Bone Marrow↗

Anaesthetic deaths.

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Anesthesia, Dental↗

Total intravenous anaesthesia with etomidate-fentanyl. Use in general and gynaecological surgery.

A total intravenous anaesthetic technique using etomidate, fentanyl and neuromuscular blocking drugs with artificial ventilation of the lungs has been used in 90 patients undergoing elective general and gynaecological surgery. A two-step schedule was used, based on a pharmacokinetic model for rapidly eliminated, intravenously administered drugs. Etomidate 100 micrograms/kg/minute with fentanyl 1 microgram/kg/minute were given for 10 minutes, followed by a maintenance dose at a rate of one-tenth this amount. Concurrent evaluation of the technique led to variations in the adjuvant drugs used (atropine, droperidol and neuromuscular blocking agent). The basic dose schedule provided adequate surgical anaesthesia for 76% of patients (although dose adjustments were used in the remainder), with recovery times of 10 minutes or less in 57% of patients. No further opiate analgesia was needed in 40% of patients postoperatively. Those patients given atropine intravenously prior to induction had a significantly lower incidence of nausea and vomiting postoperatively.

Adjuvants, Anesthesia↗

Evaluation of a new range of air drawover vaporizers. The 'PAC' series--laboratory and 'field' studies.

The 'Ether Pac' and 'Fluo Pac' temperature compensated vaporizers have been evaluated in the laboratory and the 'field'. Rigorous testing has demonstrated that these vaporizers are robust and reliable. Shaking, tilting and overturning do not significantly affect their performance. Both vaporizers deliver lower concentrations of the vapour than the setting on the vaporizers at low tidal volumes (100 ml). The 'Ether Pac' vaporizer output declines progressively with ambient temperatures below 23 degrees C and a similar result occurs with the 'Fluo Pac' at temperatures below 20 degrees C. Clinical trials in Nepal, Kenya, Burma and the UK have demonstrated that, when halothane is used, oxygen enrichment is necessary during spontaneous and controlled ventilation. When ether is used with controlled ventilation oxygen enrichment is probably not necessary even with ambient pressures as low as 619 mmHg.

Adolescent↗

Midazolam--does it cause resedation?

The objective of this double blind study was to compare the sedation following the intravenous injections of midazolam in three dose levels (0.07, 0.10 and 0.15 mg/kg), and to assess the time taken after each dose to return to street fitness. Recovery was monitored by measurement of reaction time. The mean results for each dose were compared against placebo and each other using the Student's t-test. All doses gave a significant (p less than 0.05) lengthening of reaction time compared to placebo. The two highest doses gave similar results when compared to 0.07 mg/kg, but not when compared to each other. Reaction times always returned to control values within 3 hours of injection. The Deletion of Ps test was also employed. A significant correlation was found between the results of reaction time testing and the Deletion of Ps test.

Adolescent↗

Anaesthetic deaths.

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Anesthesia, Dental↗