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Biomedical subjects

S Gershon

Publications and source records attributed to S Gershon.

At least 91 records · Page 5Linked to original sources

Increased sensitivity of the elderly to the central depressant effects of diazepam.

The effects of diazepam on memory and psychomotor performance in healthy elderly (N = 12) and young (N = 12) individuals were examined. Diazepam was administered acutely in a single, oral 2.5 mg dose. Diazepam impaired memory, both immediate and delayed recall, and psychomotor performance in the elderly subjects. In addition, the drug caused an increase in self-reported sedation in elderly subjects but not in young subjects. These findings suggest an age-related increase in the sensitivity of elderly individuals to the central depressant effects of diazepam.

Administration, Oral↗

The effect of 5,7-dihydroxytryptamine on the serum corticosterone resistance to suppression by dexamethasone.

The effect of serotonin (5-HT) deficiency on hypothalamic-pituitary-adrenal (HPA) activity was investigated by using 5,7-dihydroxytryptamine (5,7-DHT) for the selective destruction of central 5-HT neurons, and corticosterone response to suppression by dexamethasone as the index of HPA activity. Dexamethasone was shown to significantly suppress serum corticosterone levels in sham-treated rats, but did not suppress corticosterone in the 5,7-DHT-lesioned animals. This finding supports the conclusion that 5-HT is involved in the negative feedback mechanism of HPA regulation.

5,7-Dihydroxytryptamine↗

Prediction of serum cortisol response to dexamethasone in normal volunteers: a multivariate approach.

Dexamethasone (DEX, 0.5 mg orally at 11 PM) challenge was used for the assessment of hypothalamic-pituitary-adrenal (HPA) activity in 20 normal volunteers. Age and pre-DEX serum cortisol levels were theè evaluated as predictors of postDEX serum cortisol levels using step-wise multiple regression analysis. Both age and preDEX serum cortisol levels were significant predictors of postDEX serum cortisol levels. It is suggested that the adjustment for age and preDEX serum cortisol level could be useful for the interpretation of abnormal postDEX levels.

Adolescent↗

Adverse effects of single therapeutic doses of diazepam on performance in normal geriatric subjects: relationship to plasma concentrations.

Elderly normal volunteers (N = 12, mean age 70.4 years) were administered placebo or diazepam 2.5, 5, 10 mg in four consecutive sessions separated by at least a 1-week interval. Memory and psychomotor performance and plasma diazepam concentrations were assessed at baseline and at 1 and 3 h following drug administration. Significant impairments were found in response to all doses of diazepam. The maximum impairment occurred at 1 h, which coincided with the highest plasma concentration of the drug.

Aged↗

Effects of pinealectomy and aging on the serum corticosterone circadian rhythm in rats.

Male Sprague-Dawley rats were housed in alternate light/dark conditions (light on, 7:00 AM, light off, 7:00 PM). Corticosterone was determined by radioimmunoassay from blood samples that were obtained by tail clip at 4-h intervals. Pinealectomized animals have shown significant increase of corticosterone levels at 7:00 AM, 11:00 AM and 7:00 PM in comparison with 2-month-old intact rats. There were no differences in serum corticosterone rhythm between 24-month-old and pinealectomized animals. Twelve-month-old rats have shown significant increase of corticosterone levels at 7:00 and 11:00 AM in comparison with 2-month-old animals. The age-associated increase of serum corticosterone and the similarity between serum corticosterone circadian rhythm in aged and pinealectomized animals suggest that an age-related decrease in melatonin production [Reiter et al., 1981] may contribute to age related changes of hypothalamic-pituitary adrenal axis regulation.

Aging↗

Changes in the drug treatment of anxiety disorders.

One of the major changes in the clinical treatment of anxiety has been the substitution of benzodiazepines for less safe sedative-hypnotic drugs. A second major change has been the finding that antidepressants suppress panic attacks. The evidence for this is reviewed in this paper. It appears that panic anxiety is qualitatively different from other kinds of anxiety; this has important implications for diagnosis and treatment. Other clinical issues presented in this symposium are a review of benzodiazepine and new, non-benzodiazepine anxiolytic drugs, the treatment of separation anxiety, and the relationship of mitral valve prolapse to anxiety. Further advances are likely to depend both on our understanding of benzodiazepine and gamma-aminobutyric acid receptors and on drug models for inducing anxiety. The fact that antidepressants suppress panic attacks, and the ability to produce panic attacks in the laboratory opens up a number of possibilities for the investigation of the physiological basis of panic attacks. All of these topics are taken up in this symposium.

Agoraphobia↗

Comparative side effect profiles of trazodone and imipramine: special reference to the geriatric population.

Side effects are a concomitant of almost all therapeutic agents and are also present as part of the pharmacological profile of psychotropic agents. However, the laboratory pharmacological characteristics of agents are a more reliable predictor of side effect profiles than they are of their therapeutic activities. Therefore, it would seem possible to be able to predict with much greater accuracy the clinically significant side effects that may be encountered from the preclinical data. This has been established in the case of trazodone and imipramine. The anticholinergic profile of imipramine was clearly determined in the laboratory and in man it produces a range of activity varying from mild peripheral anticholinergic activity to impairment of various functions involving vision, cardiovascular function and gastrointestinal activity. However, in the geriatric population, because of the vast amount of research implicating cholinergic mechanisms in memory functions and particularly in some aspects of cognitive deficit, it may be predicted that the anticholinergic activity of the tricyclics may present an especially troublesome pattern in a geriatric population that requires antidepressant therapy. These comparative effects between the two agents will be discussed and documented from control study data.

Aged↗

Acetylcholine and alpha 1-adrenergic sensitivity in the separation of depression and anxiety.

Three relatively clear-cut diagnostic groups, namely primary major depressive disorder-endogenous subtype (PRI MDD-E), primary anxiety disorder with no depression (PRI ANX), and normal controls as well as two additional patient groups with mixed or coexisting anxious/depressive diagnoses were studied. Clinical assessment was made by routine psychiatric interview, Schedule of Affective Disorder and Schizophrenia (SADS) research interview, and obtaining family history of MDD. Subjects underwent both routine 'baseline' sleep EEG polygraphic arecoline, a muscarinic, cholinergic agonist infused during sleep. Cholinergic sensitivity was assessed by measuring the time to induction of REM sleep after arecoline infusion. In addition, a subgroup of MDD patients underwent pupillographic testing. Peripheral alpha-adrenergic responsivity was measured by the magnitude of pupillary mydriatic response after local ocular instillation of phenylephrine. Successful separation (83% correct classification) of the 'pure' groups (PRI MDD-E, PRI ANX, and normal) was achieved by discriminant function analysis of sleep EEG variables. Compared to PRI ANX and normal groups, patients with PRI MDD-E had supersensitive cholinergic REM-induction response, shorter REM latency, increased first REM density and REM percent. Separation of the PRI ANX and normal groups was by intermittent awake time, delta sleep percent, and total REM density. Classification of the mixed anxious/depressive groups was next attempted using the discriminant coefficients derived from the above analysis of 'pure' groups. We found that the presence of absence of family history of MDD in patients with mixed diagnosis offered the best prediction of classification into PRI MDD-E and PRI ANX groups, respectively. MDD patients with coexisting panic disorder were significantly subsensitive to phenylephrine-induced mydriasis compared to MDD patients without anxiety.

Acetylcholine↗

Myalgia and elevation in muscle creatine phosphokinase during zimelidine treatment.

The authors report a case involving a 65-year-old woman with DSM-III criteria for major unipolar depression in whom the administration of zimelidine, a potent and selective 5-hydroxytryptamine reuptake inhibitor, led to the development of a hypersensitivity reaction characterized by a severe headache, low grade fever, abnormal liver enzymes, and generalized myalgia 10 days after initiation of treatment. The most novel aspect of this hypersensitivity reaction to zimelidine was the development of abnormalities in muscle creatine phosphokinase in conjunction with the myalgia.

Aged↗

Chemotherapy of cognitive disorders in geriatric subjects.

Many of the neurochemical changes associated with aging brain, particularly lower choline acetyltransferase and higher monoamine oxidase, occur with greater severity in senile dementia, Alzheimer's type (SDAT). These alterations correlate with neuropathologic indices, e.g., the number of senile plaques and tangles. Although many different treatment techniques have been used, most have been unsuccessful. No strong data have supported the use of stimulants, Gerovital H3, or hyperbaric oxygen. Among the vasodilators, cyclandelate and hydergine may be of value in some but not most patients. Much recent work has focused on techniques to increase acetylcholine brain concentrations. To date, precursors, such as choline, seem to have very limited value. Postsynaptic treatments, e.g., physostigmine, hold more hope for future benefit, if longer acting oral preparations are developed. Other compounds, such as ACTH, vasopressin, and piracetam, may have some value but need better definition and treatment indications. Recent discoveries on the influences of lecithin on membrane fluidity and receptor binding, may affect the focus of future pharmacologic investigation.

Adrenocorticotropic Hormone↗

Lithium-induced increases in red blood cell choline and memory performance in Alzheimer-type dementia.

To investigate the relationship between RBC choline and memory in Alzheimer-type senile dementia (SDAT), lithium carbonate was administered to 14 SDAT patients in doses of 400-600 mg/day for 5 weeks. A battery of memory tests was administered at baseline and at weekly intervals. Five patients with serum concentrations below 0.6 meq/liter developed neurotoxicity and were dropped from further analysis. For the remaining patients, Li+ with mean serum concentrations up to 0.6 meq/liter did not alter memory scores significantly. The dramatic increases in RBC choline during the study, however, suggest that RBC choline is not correlated with memory functioning in SDAT.

Aged↗