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Biomedical subjects

H P Davis

Publications and source records attributed to H P Davis.

At least 37 records · Page 2Linked to original sources

Modified T-maze training demonstrates dissociated memory loss in rats with ischemic hippocampal injury.

Rats were trained for 20 days on a modified T-maze which required discrimination of a stem choice that was invariant and a goal choice that alternated. Animals were then exposed to 30 min of transient severe forebrain ischemia (postischemic, PI animals), 30 min of less severe ischemia (non-criterion ischemic, NCI animals), or sham operations (controls). After 30 postoperative days, all animals were returned to the maze for an additional 30 trials. PI rats demonstrated a dissociated performance on stem and goal choice. Specifically, the PI animals were significantly impaired on discrimination of a goal choice, yet performed comparably to controls on discrimination of a stem choice. Impaired goal choice for PI animals was not due to differential run times, proactive interference, or interaction between goal and stem choice. Histopathologic analysis of PI animals revealed bilateral destruction of the pyramidal neurons in the dorsal CA 1 region of the hippocampus and lesser damage in the anterodorsal subiculum and the dorsolateral caudate. NCI animals had patchy variable ischemic neuronal damage. These data suggest that ischemic-induced bilateral CA 1 pyramidal neuron loss is sufficient to cause dissociated performance in trained animals on a T-maze, but that less severe ischemia does not cause reproducible hippocampal neuron damage or functional deficits. Further, the data extends the development of reliable behavioral measures for an animal model of the amnesic syndrome that may occur in humans after cardiac arrest.

Amnesia↗

Safe application of a 13-Gy split dose total body irradiation schedule prior to bone marrow transplantation.

Two conditioning regimens for bone marrow transplantation for patients with acute lymphoblastic leukaemia were compared. Both regimens (VVRAPID and VVRAPID-X) incorporated the same cytotoxic chemotherapy but differed in the radiation dose; VVRAPID employed a single fraction of 10.5 Gy and VVRAPID-X employed 10.5 Gy followed 4 days later by a further dose of 2.5 Gy. The 13-Gy split-fraction schedule was well tolerated with no significant increase in infection or requirement for blood products. An increase in gastrointestinal toxicity occurred but responded to increased oral anti-diarrhoeal agents. Overall survival and relapse rates did not differ significantly between the two groups. There was a trend for the 13-Gy schedule to reduce the graft failure rate following T cell-depleted bone marrow transplants.

Adolescent↗

Retention of reference memory following ischemic hippocampal damage.

Retention of reference memory was evaluated in an animal model of cerebral ischemia. Rats were trained for 70 daily trials on an 8-arm radial maze with 5 arms baited, subjected to 30 minutes of forebrain ischemia, allowed to recover for 30 days, and then tested for an additional 50 trials. Post ischemic (PI) rats demonstrated normal retention of reference memory (p less than 0.05). Working memory was significantly impaired postoperatively (p less than 0.05). Morphologic analysis showed that PI rats had primary loss of pyramidal neurons in the CA1 region of hippocampus.

Animals↗

Polycythaemia following renal transplantation.

Polycythaemia has developed in 10 of 59 regularly reviewed patients with renal transplants surviving more than three months. The pathology of the raised haemoglobin level was heterogeneous. Three patients had a picture characterized by a normal red cell mass and reduced plasma volume. Seven patients had a raised red cell mass; in 3 of these this was associated with a period of abnormal liver function and fitted with the state of raised red cell mass in association with hepatic transaminitis. The remaining 4 patients form a unique, previously undefined group with no features to explain the underlying aetiology of the polycythaemia. The patients had a trouble-free post-transplant course with early establishment of graft function. It is proposed, from the data obtained from in vitro culture studies, that the early return of good renal function allows the erythroid compartment to expand in response to circulating erythropoietin. The establishment of an erythron of increased size allows for a persistently raised haemoglobin in the presence of normal erythropoietin levels.

Bone Marrow↗

Reference and working memory of rats following hippocampal damage induced by transient forebrain ischemia.

Acquisition of reference and working memory was evaluated in an animal model of cerebral ischemia. Rats were subjected to 30 minutes of transient forebrain ischemia, allowed to recover, and then tested for 95 trials on an 8-arm maze with 5 arms baited. During the 95 trials post ischemic (PI) rats made significantly more working and reference errors than controls (p less than 0.05). However, an analysis of the last 20 trials (75-95) showed that while PI rats and control rats had comparable reference memory (p greater than 0.8). PI rats tended to have a persistent working memory deficit compared to controls (p less than 0.06). Subsequent morphologic analysis showed that PI rats had almost complete loss of pyramidal neurons in the anterior CA1 region of the hippocampus, moderate to severe loss in mid-dorsal posterior hippocampus, and less damage to the dorsolateral striatum. These results suggest that the PI animal is a reasonable model for the permanent behavioral impairment and pathologic damage found in some human survivors of cardiac arrest.

Animals↗

Behavioral studies with mice exposed to DC and 60-Hz magnetic fields.

Behavioral measures were evaluated in adult CD-1 and LAF-1 mice continuously exposed for 72 h to a 1.5-Tesla (1 T = 10(4) Gauss) homogeneous DC magnetic field, and in LAF-1 mice continuously exposed for 72 h to a sinusoidal 60-Hz, 1.65-mT (rms) homogeneous AC field. Three types of behavioral tests were employed: (1) Memory of an electroshock-motivated passive avoidance task was assessed in animals that had been trained immediately prior to the field exposure. The strength of memory was varied either by altering the strength of the electric footshock during training, or by administering a cerebral protein synthesis inhibitor, anisomycin, at the time of training. (2) General locomotor activity was measured using a quadrant-crossing test immediately after termination of the magnetic field exposure. (3) Sensitivity of the experimental subjects to the seizure-inducing neuropharmacological agent, pentylenetrazole , was assessed immediately after the field exposure on the basis of three criteria: (a) the percentage of subjects exhibiting a generalized seizure, (b) the mean time to seizure, and (c) the mean seizure level. The results of these studies revealed no behavioral alterations in exposed mice relative to controls in any of the experimental tests with the 1.5-T DC field or the 60-Hz, 1.65-mT (rms) AC field.

Animals↗

Investigation of the reported protective effect of cycloheximide on memory.

Many findings support the hypothesis that formation of long-term memory requires synthesis of proteins in the nervous system close to the time of learning. This hypothesis has been challenged recently by reports that the protein synthesis inhibitor cycloheximide (CYC) injected 2 hr prior to passive avoidance training in mice or rats attenuated the memory impairment induced by a usually amnestic dose of CYC administered 30 min pretraining. To investigate the reports of a "protective" effect of the prior injection, we attempted to replicate them and test their generality. For replication we administered either paired injections of CYC--120 mg/kg 2 hr prior to training and 30 mg/kg 30 min prior to training--or single injections of CYC (either 120 mg/kg or 30 mg/kg) 30 min pretraining and tested for retention of the passive avoidance habit either 1 or 7 days later. No attenuation of amnesia was observed at 1 day tests. Attenuation of amnesia following the double injection of CYC was observed at 7 day tests. When another protein synthesis inhibitor, anisomycin, was used in the same experimental design, there was no "protective" effect; two injections of anisomycin produced greater memory impairment for the passive avoidance habit than did the single low dose. Also, for active avoidance training, two successive injections of CYC caused significantly greater amnesia than did a single dose; this is the opposite of a "protective" effect. We suggest that the reported "protective" effect of CYC on memory is an as yet unexplained phenomenon that does not generalize to other antibiotic drugs and is specific to the passive avoidance task.

Animals↗

The Health Role Expectations Index: A measure of alignment, disparity, and change.

Growing controversy over mutual role expectations of physician, nurse, and consumer underlines the need to clarify attitudes toward their responsibilities in health care. This article describes the development and testing of the Health Role Expectations Index, a measure of attitudes regarding the amount of shared responsibility which should exist in the relationships of nurse, physician, and consumer. Testing for validity through differential prediction to known groups and prediction to external measures is detailed. Internal consistency and test-retest reliability findings are also presented. While both the validity and the reliability of the Health Role Expectations Index are supported, the preliminary nature of test results and areas for further testing of the tool are emphasized. Implications for the instrument's use are then discussed.

Attitude to Health↗

Improvement of 8-arm maze performance in aged Fischer 344 rats with 3,4-diaminopyridine.

Short-term memory of a spatial task by male Fischer 344 rats at 3, 12, and 24 months of age was examined in a radial 8-arm maze. Performance by 24 month old rats was significantly poorer than that of 3 or 12 month old rats. 3,4-Diaminopyridine (1000 pmole/kg), a compound that stimulates acetylcholine release, significantly improved 8-arm maze performance by 24 month old rats. Thus, an age-related deficit in short-term memory for a spatial task can be ameliorated by a compound that stimulates acetylcholine release.

4-Aminopyridine↗

Inhibition of cerebral protein synthesis does not prolong short-term memory.

Male Swiss albino CD-1 mice given a single subcutaneous injection of a cerebral protein synthesis inhibitor, anisomycin (ANI; 1 mg/animal), 20 min prior to a single trial of passive avoidance training demonstrated impaired retention at tests given 3 hr, 6 hr, 1 day, and 7 days after training. Retention was not significantly different from that of saline controls when tests were given .5 or 1.5 hr after training. Prolonging inhibition of brain protein synthesis by giving either one or two additional injections of ANI at 2 hr or at 2 and 4 hr after training did not prolong good retention performance. The temporal development of impaired retention in ANI-treated mice could not be accounted for by drug dosage, duration of protein synthesis inhibition, or nonspecific sickness at test. In contrast to the suggestion that protein synthesis inhibition prolongs short-term memory, the results of this experiment indicate that short-term memory is not prolonged by antibiotic drugs that inhibit cerebral protein synthesis. All evidence seems consistent with the hypothesis that short-term memory is independent of protein synthesis and that the establishment of long-term memory depends on protein synthesis during or shortly after training.

Animals↗

Effects of anisomycin on retention of the passive-avoidance habit as a function of age.

Three age groups of male Swiss albino CD-1 mice (2-3 mo, 6-7 mo, and 14-15 mo) were treated with a 120 mg/kg dose of the protein synthesis inhibitor anisomycin or with an equal volume of saline at various times before and after training (20 min pretraining, 0, 10, 30, or 180 min posttraining) in a shock motivated passive-avoidance task. Young (2-3 mo) and intermediate-aged (6-7 mo) mice treated with anisomycin before or immediately after training demonstrated impaired retention at a 7 day test, but retention was normal for mice injected 10, 30 or 180 min posttraining. The older mice (14-15 mo) showed similar results, with one exception: those older mice injected with anisomycin 10 min posttraining were significantly impaired in retention as compared to older saline controls and to identically treated young or intermediate-age mice. The prolonged gradient of retrograde amnesia demonstrated by older mice could not be accounted for by impaired acquisition, impaired short-term memory, altered spontaneous locomotor activity, or differential inhibition of brain protein synthesis.

Aging↗