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Biomedical subjects

M Stanley

Publications and source records attributed to M Stanley.

At least 109 records · Page 6Linked to original sources

Proactive and retroactive effects of repeated electroconvulsive shock on passive avoidance retention in rats.

In spite of technical modifications, the therapeutic administration of electroconvulsive shock (ECS) to humans is still associated with significant memory impairment. Studies aimed at elucidating the neurobiologic basis of this impairment and developing appropriate treatment approaches have been limited by the absence of an appropriate animal model. We report here that ECS administered daily for 1-7 days to male albino rats (ECS X 1-ECS X 7) cumulatively impaired retention of passive avoidance when animals were trained 24 hours after the last ECS and tested 24 hours after training. Retention was directly proportional to the interval between training and testing; animals trained 24 hours after ECS X 7 and tested 1 hour later showed no deficit while animals tested after 24 hours showed maximal impairment. Retention was significantly improved by 10 days following the last of ECS X 7 and intact by 21 days. These findings parallel the effects of ECS on memory function in humans. The retrograde effects of ECS also paralleled those demonstrated in humans; while retention of a passive avoidance task learned 24 hours before ECS X 7 was grossly impaired, retention was intact if learning took place 7 days before the ECS course. The application of these findings as an animal model of ECS-induced memory impairment in humans, is discussed.

Amnesia↗

Serotonergic mechanisms in the behavioral effects of buspirone and gepirone.

The literature describing the role of serotonin (5-HT) in the mediation of anxiety is a controversial one. Serotonergic involvement in the mechanism of action of two nonbenzodiazepine anxiolytics, buspirone and gepirone, supports a role for serotonin in anxiety. The anticonflict effect of both drugs is blocked by serotonin lesions, and gepirone induces the serotonin syndrome. A shift in the gepirone dose-response curve to the left in serotonin lesioned rats suggests that this may be 5-HT-receptor mediated. Both buspirone and gepirone enhance the acoustic startle response and gepirone's effect is attenuated in serotonin lesioned animals. While other components of buspirone's mechanism of action may suppress the behavioral expression of its serotonergic interactions, results from these studies suggest that serotonin agonist-like activity may be an important mechanism in the actions of a clinically proven nonbenzodiazepine anxiolytic (buspirone), and anxiolytic candidate (gepirone).

5,7-Dihydroxytryptamine↗

Prospective strategies for cholinergic interventions in Alzheimer's disease.

The cholinergic hypothesis of memory dysfunction has guided most of the recent proposals for treating the primary symptoms of AD. The efficacy of these treatments has been severely limited. This review examines two major lines of evidence which suggest that the cholinergic hypothesis may have to be expanded and revised. The cholinergic hypothesis focuses on pre-synaptic defects. It assumes cholinoceptive neurons would function normally with adequate stimulation. Evidence is not sufficient to support this assumption. In addition, dissociations have been demonstrated between muscarinic receptor number and functional response of cholinoceptive neurons. Various measures are proposed to investigate the functional integrity of muscarinic receptors in AD patients. AD often has been characterized as a disorder produced by generalized cholinergic hypoactivity. Evidence for cortisol hypersecretion, abnormal dexamethasone suppression, and the occurrence of depressive symptoms, motoric dysfunction and sleep abnormalities in AD patients is more consistent with regional cholinergic hyperactivity than generalized hypoactivity. Resolution of these discrepancies could shed new light on the pathophysiology and treatment strategies for AD. Cholinoceptive neurons could be hypersensitive, subsensitive or have unaltered responsivity. These options would have very different treatment implications. New developments in outcome assessment which are capable of discriminating varieties of differential response to treatment can spur treatment development and improve quality of care for patients with complex disorders such as AD.

Alzheimer Disease↗

Improved survival after allogeneic small intestinal transplantation in the rat using cyclosporine immunosuppression.

We investigated the effect of cyclosporine on survival after intestinal transplantation between histoincompatible Brown Norway (AgB3/3) and Lewis (AgB1/1) rats. Intestinal grafts were primarily vascularized (by microsurgical techniques) and interposed isoperistaltically in the recipient's jejunum. All animals were weighed and observed daily. Survival of recipients given cyclosporine 20 mg/kg/d (112 +/- 92 days, n = 10) was significantly longer (P less than .02) than that of recipients given no drug (12 +/- 4 days, n = 8). Six out of ten cyclosporine-treated animals remained alive and well at the conclusion of the experiment. One of these was killed and showed no gross or microscopic evidence of rejection. The described experimental model involves a simple operative technique and minimal postoperative care and should permit systematic investigation of the detection and prevention of rejection.

Animals↗

Concomitant neuropeptide-producing endometrial carcinomas and ileal carcinoid tumors.

The concomitant occurrence of neuropeptide-reactive endometrial carcinoma and ileal carcinoid tumor represents an observation that has been unreported until now. We have seen two patients with this rare combination of tumors. The endometrial carcinomas in these cases manifested focal immunoreactivity for neuron-specific enolase; in addition, one contained rare cells showing positive staining for gastrin, and the other displayed focal content of substance P. The carcinoid tumors seen in each case demonstrated immunocytochemical positivity for neuron-specific enolase and vasoactive intestinal polypeptide, and one also exhibited immunoreactivity for gastrin. Whether this association of neoplasms represents a syndromic complex or a coincidence is a matter of speculation at present.

Aged↗

The dexamethasone suppression test (DST) in predicting response to desipramine and amitriptyline in depressed outpatients.

The predictive value of the dexamethasone suppression test (DST) was evaluated in two consecutive clinical trials involving 99 individuals treated with amitriptyline or desipramine. Following one week observation, and following one week on low-dose desipramine or amitriptyline (50 mg), all patients who remained depressed (Hamilton score 16 or greater) were given a full clinical trial of either desipramine or amitriptyline (150-300 mg/day) over a minimum 3-5 week period. In all, 68 patients required this trial, 31 receiving amitriptyline and 37 receiving desipramine. For these patients there was no relationship between DST suppression/non-suppression vs clinical response to either desipramine or amitriptyline. There was a non-significant trend for suppressors (negative DST) to respond either spontaneously or to low-dose desipramine or amitriptyline as opposed to non-suppressors (positive DST).

Amitriptyline↗