Intrasubject reproducibility of growth hormone-releasing hormone-stimulated growth hormone in older women, older men, and younger men.

Intrasubject reproducibility of growth hormone (GH) response to growth hormone-releasing hormone (GHRH) was studied in healthy older women (n = 9), older men (n = 8), and younger men (n = 10). Subjects received IV injections of 0.1 ml/kg saline, 1 micrograms/kg GHRH, and 2 micrograms/kg GHRH, three times each, and blood was sampled at 0, 15, 30, 45, 60, and 120 min for GH concentration. There was no significant difference in peak GH response between the 1- and 2-micrograms/kg GHRH dosages. GH responsiveness, group variance of peak GH, and intrasubject variability were greatest for younger men, less for older men, and least for older women at both dosages of GHRH. Because of the large intrasubject variability observed in this study, it appears necessary to test subjects more than once to obtain a valid characterization of GH responsiveness.

Serum anticholinergic activity in hospitalized older persons with delirium: a preliminary study.

OBJECTIVE: To evaluate the relationship between total serum anticholinergic activity (SAA) and the presence or absence of delirium in older hospitalized persons on general medical wards. DESIGN: Case-control study and within-subjects repeated-measures in recovered delirious patients. SETTING: Minneapolis Veterans Affairs Medical Center medical wards. PARTICIPANTS: Eleven male delirious patients (DSM-III-R criteria) aged 60 or older and 11 comparably aged male nondelirious controls. MEASUREMENTS: Radioreceptor bioassay of total SAA using tritiated quinuclidinyl benzilate (QNB) binding to muscarinic receptors. Results are expressed in terms of atropine equivalents (nM). MAIN RESULTS: Mean SAA was significantly elevated in the delirious group (mean +/- SD = 6.05 +/- 2.97 nM atropine equivalents) compared with the controls (3.38 +/- 2.49; t(20) = 2.28, P < .05). At study entry, mean SAA was significantly higher in delirious subjects whose symptoms eventually resolved completely (mean +/- SD = 7.77 +/- 2.37) compared with subjects whose delirious symptoms persisted (3.99 +/- 2.30; t(9) = 2.68, P < .05). All six patients in whom delirium resolved completely had a decrease in serum anticholinergic activity when measured during delirium (7.77 +/- 2.37) and after symptom resolution (3.92 +/- 2.61; t(5) = 3.29, P < .05). CONCLUSIONS: Our findings suggest that serum anticholinergic activity may play a role in delirium in medical inpatients. The relationships between SAA and delirium in medical patients and between total SAA and medication use warrant further study.

Serum anticholinergic activity and behavior following atropine sulfate administration in the rat.

Anticholinergic agents such as atropine and scopolamine have long been suggested to produce delirium-like states in humans and experimental animals. Evidence for an anticholinergic mechanism in the pathogenesis of human delirium has accumulated, leading to studies of the behavioral effects of the anticholinergic drug atropine in animals. The current study addresses the adequacy of animal models of delirium in terms of sensitivity, specificity and pharmacological relevance. A multiple fixed-ratio fixed-interval reinforcement schedule was used to test the effects of relatively low doses of atropine on behavior in rats. Additionally, total serum anticholinergic activity (SAA) was measured under dose and time course conditions identical to those used in the behavioral study. Atropine reduced high and low rates of responding in a dose-dependent manner, and SAA increased in a dose dependent manner. SAA at atropine doses of 0.1 mg/kg to 1.0 mg/kg was similar to that found in delirious humans. These behavioral and serum level data suggest that relatively low doses of atropine, substantially below those used in previous attempts to model delirium using rats, may be more pharmacologically relevant to delirium and may minimize non-specific peripheral effects of this drug.

Alternating lever cyclic-ratio schedule analysis of the effects of atropine sulfate.

Cholinergic dysfunction has been implicated in the behavioral and memory impairment that is the hallmark of conditions such as delirium and Alzheimer's Disease. Anticholinergic drugs have been widely used in procedures designed to mimic aspects of the pathology of these conditions in rats. Procedures in use vary widely in sensitivity and behavioral specificity and may be confounded by administration of high drug doses that may not be physiologically relevant. The current study proposes the use of rats responding on an alternating lever cyclic-ratio schedule to study the effects of the anticholinergic compound atropine sulfate. This procedure enables simultaneous measurement of anticipatory ratio tracking (postreinforcement pause durations), perseverations (lever switching errors), and nonspecific peripheral drug effects (running response rates). Results of this study suggest that the schedule is sensitive to low drug doses (0.1-1.0 mg/kg atropine), measures the ability to track changing ratio conditions and to execute lever alternation, and allows for monitoring of peripheral drug effects during behavioral testing. The procedure's sensitivity and low effective dose range may make it useful in the study of behaviors related to anticholinergic effects.

Dialysis dementia.

Dialysis dementia is a unique neurologic complication of renal failure associated with chronic dialysis. While many questions remain about the pathophysiology of the disease, aluminum toxicity is probably the major factor in the pathogenesis of the dementia. Reducing dialysate aluminum levels and minimizing oral aluminum intake has markedly decreased the incidence of the disease. Deferoxamine, a chelating agent, is effective if it is given early; however, chronic use may lead to serious complications, although they are rare.

Delirium and right-hemisphere dysfunction in cognitively impaired older persons.

Cognitive impairment has been repeatedly shown to be a delirium risk factor. Much indirect evidence suggests that right-hemisphere dysfunction plays a particularly important role. This retrospective, case-controlled study, from a 148-patient memory loss clinic database, compared neuropsychological measures of hemispheric function in cognitively impaired elderly veterans with and without a history of delirium. Eleven study subjects had a history compatible with DSM-III-R criteria for delirium. Controls selected from the same database had no known history of delirium and were matched for Mini-Mental State Examination scores and Geriatric Depression Scale scores. Compared to the controls, subjects with a history of delirium had significantly lower scores on Object Assembly and Visual Reproduction (p < .05), tests that are predominantly right-hemisphere dependent. There were no significant differences in left-hemisphere measures. It is concluded that right-hemisphere dysfunction may prove to be an important risk factor for delirium.

The association of serum anticholinergic activity with delirium in elderly medical patients.

To investigate the hypothesis that elevated serum anticholinergic activity is independently associated with delirium in ill elderly persons, the authors performed a cross-sectional study of 67 acutely ill older medical inpatients. The presence of delirium was evaluated with the Confusion Assessment Method, and the presence of many delirium symptoms was measured by the Delirium Symptom Interview. Demographic data and clinical characteristics that may be important for the development of delirium were also collected. Logistic regression techniques demonstrated that elevated serum anticholinergic activity was independently associated with delirium. Among the subjects with delirium, a greater number of delirium symptoms was associated with higher serum anticholinergic activity.

Measuring delirium severity in older general hospital inpatients without dementia. The Delirium Severity Scale.

The authors evaluated the validity, reliability, and sensitivity to change of the Delirium Severity Scale (DSS), a 10-minute assessment consisting of Forward Digit Span and Similarities. Twenty-two older inpatients with delirium but not dementia and 15 control patients were administered the DSS during hospitalization. Scores were significantly inversely correlated with experts' quantitative ratings of severity at all three time-points examined. The DSS showed significant improvement over time (P < 0.001) and significant correlation with improvement in expert ratings (P = 0.026). The DSS shows promise as a valid and reliable measure sensitive to changing symptom severity.