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Biomedical subjects

D Pickar

Publications and source records attributed to D Pickar.

At least 235 records · Page 13Linked to original sources
PubMed1982

Physiological effects of high dose naloxone administration to normal adults.

The intravenous bolus administration of high doses of the opioid receptor antagonist naloxone (in the mg./kg. range) to normal adults produced dose-dependent increases in systolic blood pressure and respiratory rate. No significant alterations in other physiological processes were found although there were trends for increases in oral temperature and pulse rate with increasing dose. These results suggest the involvement of an endogenous opioid system in the tonic regulation of human systolic blood pressure and respiration and the probable inadequacy of doses of naloxone previously utilized in human studies to effect complete blockade of endogenous opioid systems.

Adult↗
PubMed1982

Cardiovascular changes in response to selective monoamine oxidase inhibition in the rat.

Chronic (21 days) treatment with the selective monoamine oxidase (MAO)-A inhibitor clorgyline, but not with the MAO-B inhibitor deprenyl in pithed rats leads to increased blood pressure responses to sympathetic stimulation and intravenous tyramine, and to elevated unstimulated heart rates. No significant changes are observed in plasma catecholamine responses to sympathetic stimulation, nor in beta-adrenoreceptor numbers in heart ventricles. These findings suggest that the hypotensive effects of MAO inhibitors result from central nervous system rather than peripheral nervous system alterations.

Animals↗
PubMed1982

Short-term naloxone administration in schizophrenic and manic patients. A World Health Organization Collaborative Study.

A double-blind study of the behavioral effects of short-term naloxone hydrochloride administration was performed in 32 schizophrenic and 26 manic patients in a World Health Organization collaborative project. There was a significant naloxone-associated reduction in overall physician-rated symptoms in schizophrenic patients concurrently treated with neuroleptic medication (N = 19) but not in medication-free schizophrenics (N = 13). Physician rating of auditory hallucinations showed significant naloxone-associated improvement for the total schizophrenic population, while self-ratings of auditory hallucinations showed improvement only in neuroleptic-treated schizophrenics. While further studies are needed to delineate these effects as to clinical significance, they may bear etiological implications for the psychobiology of schizophrenia, including the possibility of synergistic effects of dopamine and endorphin blockade. Naloxone produced no significant behavioral effects in manic patients. These findings are discussed with relationship to the hypotheses of endorphin involvement in schizophrenia and mania.

Adult↗
PubMed1982

Selective and nonselective monoamine oxidase inhibitors: behavioral disturbances during their administration to depressed patients.

The occurrence of behavioral disturbances during four-week treatment of depressed patients with the nonselective monoamine oxidase (MAO) inhibitor, phenelzine sulfate (N = 14), the selective MAO-type A inhibitor, clorgyline (N = 12), and the partially selective MAO-type B inhibitor, pargyline hydrochloride (N = 13), was studied. Behavioral disturbances were encountered during treatment with each of the MAO-inhibiting drugs, with an overall incidence of 15% (six of 39 patients). All but one episode met criteria for mania or hypomania. Patients with bipolar illness experienced significantly greater incidences of behavioral disturbances in comparison with patients with unipolar illness (35.3% v 4.5%, respectively). The earliest latency to onset of a behavioral disturbances was 18 days, whereas the mean latencies were 22 to 26 days. Episodes of hypomania were observed after discontinuation of drug treatment in individual patients with unipolar and bipolar illness. Repeated MAO-inhibitor treatment, as part of a crossover study of clorgyline and pargyline, produced an increased severity of behavioral disturbances and a significantly shortened latency to onset.

Acute Disease↗
PubMed1982

Effort and cognition in depression.

Motor performance and cognitive function were examined in depressed patients and controls. Increasing severity of depression was strongly associated with decrements in performance in both motor and memory tasks. Greatest depression-related impairment was found on those cognitive and motor tasks that required sustained effort. We discuss these results in terms of a generalized deficit in the central motivational state of depressed individuals.

Adult↗
PubMed1982

REM sleep suppression induced by selective monoamine oxidase inhibitors.

The effects of 4 weeks of treatment with the selective monoamine oxidase (MAO) inhibiting antidepressant clorgyline and pargyline on the sleep of affectively disordered patients were studied. Both inhibitors resulted in near total suppression of REM sleep, a decrease in total sleep time, and an increase in the percent of stage 2 sleep. Clorgyline also increased awake time and decreased total recording period and sleep latency. In general, changes were greater for clorgyline than for pargyline and were about 50% slower to return to baseline after clorgyline compared to pargyline discontinuation. The results were consistent with the hypothesis that selective inhibition of the MAO type A, as produced by clorgyline, is sufficient to induce marked sleep changes. MAO inhibitor-induced receptor changes are proposed to account for the time course of the REM suppression and the REM rebound observed upon withdrawal.

Adult↗
PubMed1982

Stress-induced plasma beta-endorphin immunoreactivity may predict postoperative morphine usage.

The relationship between stress and human behavior is studied using general surgery as a stress paradigm. As indices of arousal, presurgery and surgery plasma beta-endorphin and cortisol immunoreactivity are assessed. Behavioral analysis is restricted to the measurement of total morphine usage during the first 24 postoperative hours under standard PRN (as needed) clinical orders. Individual patient morphine requirements vary widely (12-56 mg). Both presurgery and mean surgery plasma beta-endorphin levels significantly predict morphine requirement, and similar, although not so strong, correlations are found for cortisol. Patient age is also found to be negatively correlated with morphine requirement. When multiple regression analysis is used, the variables of plasma beta-endorphin and age predict 70% of the variance in individual morphine requirements.

Adolescent↗
PubMed1982

Response of plasma beta-endorphin immunoreactivity to d-amphetamine and placebo in schizophrenic patients.

The response of plasma beta-endorphin (ir) to infusions of randomly assigned d-amphetamine (20 mg) and placebo was studied in eight schizophrenic patients. Although there was no statistically significant difference between the response to d-amphetamine and placebo, significant increases in plasma beta-endorphin (ir) levels were observed following each infusion. Although heterogeneity in beta-endorphin (ir) response was observed, individual differences did not relate to clinical variables such as abnormalities on computed tomography or "process-reactive" distinctions. An excessive beta-endorphin response to placebo in schizophrenia is discussed.

Adult↗
PubMed1982

Effects of fentanyl on the response of plasma beta-endorphin immunoreactivity to surgery.

Beta-endorphin appears to play a definite role in the biologic response to stress and in the endogenous mechanism of pain perception. Opiates exogenously administered during surgery decrease or even suppress the activation of "stress hormones" such as ACTH and cortisol. In the present study, the authors tried to assess the effects of fentanyl administration on plasma beta-endorphin immunoreactivity PBE(ir) during surgical stress. In one group of nine patients, a standard enflurane-based general anesthetic technique without opiates was used for a staging laparotomy. A second group of ten patients undergoing the same type of surgery received fentanyl (10-20 micrograms/kg) as the primary anesthetic drug. In both groups, multiple blood samples were collected prior to, during, and after surgery, following the same time protocol. PBE(ir), plasma cortisol and, in five patients, plasma ACTH were determined by radioimmunoassay. There was no significant change in PBE(ir) in either group after anesthetic induction. Unlike the enflurane group, the fentanyl group did not demonstrate any significant increase from baseline in PBE(ir) during surgery. There was a significant group difference between enflurane and fentanyl in PBE(ir) levels for both "early" and "late" surgery values, but not for the "awake" values (recovery period) where both groups had elevated PBE(ir) levels. Plasma cortisol and plasma ACTH changes followed a trend similar to those of PBE(ir). The suppression of both cortisol and PBE(ir) responses during surgery after administration of fentanyl provides further evidence for the involvement of the endorphin system in the stress response and for its physiologic association with the hypothalamo pituitary axis.

Adult↗
PubMed1982

Endorphins in the cerebrospinal fluid of psychiatric patients.

In this paper we have reported the results of studies in psychiatric patient groups using the strategy of measuring opioid activity and beta-endorphin (ir) in CSF. Our findings do not lend support to the notion of excess endorphin activity in schizophrenia, but rather suggest the possibility of a decrease in endogenous opioid activity in some schizophrenic patients. In affectively ill patients our data suggest that there may be a relative change in endogenous opioid system activity across state change in manic-depressive illness. Who also found a relationship between nurses' ratings of anxiety and CSF opioid activity in depressed patients, although it is unknown whether this directly relates to the pathophysiology of this symptom, or is related to stress response. The relationship between CSF opioid activity and HPA axis activity, as reflected by urinary free cortisol excretion, supports the notion of important physiologic relationships between these systems and raises the issue of a role for the endogenous opioid system in the abnormal activation of this system in depression. Finally, the finding of increased CSF opioid activity in anorexia nervosa patients when a minimum weight coupled with data relating endogenous opioids to eating behavior raises interesting questions regarding a possible involvement of the endogenous opioid system involvement in this illness.

Adult↗
PubMed1982

High plasma norepinephrine levels in patients with major affective disorder.

The authors found that patients with major affective disorder had higher levels of plasma norepinephrine and higher pulse rates (tachycardia) than healthy control subjects, but their blood pressures were normal. These measurements were similar in all three subgroups of patients with affective disorder--manic, bipolar depressed, and unipolar. Because norepinephrine is the primary neurotransmitter of the sympathetic nervous system, these data suggest sympathetic hyperactivity in the major affective disorders. This conclusion is compatible with recent speculation based on the effect of antidepressants on noradrenergic receptors and a failure of alpha-receptors to downregulate normally in patients with major affective disorder.

Adult↗
PubMed1982

Cerebrospinal fluid opioid activity in anorexia nervosa.

The authors found higher levels of CSF opioid activity, determined by radioreceptor assay, in patients with anorexia nervosa who were severely underweight than in 1) the same patients after weight restoration and 2) normal controls. Another group of patients who had chronic anorexia nervosa but were not severely underweight had normal levels of CSF opioid activity. Endogenous opioid systems have been shown to be related to eating behavior and metabolic regulation in animals. The association between decreased weight and increased CSF opioid activity observed by the authors may be a compensatory response to weight loss or may be etiologically related to anorexia nervosa.

Adult↗
PubMed1982

Clinical studies of the endogenous opioid system.

The role of the endogenous opioid system in humans was studied using three clinical research strategies. High doses of the opiate antagonist naloxone (up to 4 mg/kg) were administered to normal volunteers. Dose-dependent increases in self-ratings of tension-anxiety and anger-hostility were observed, supporting the hypothesized involvement of the endogenous opioid system in the modulation of human mood and feelings of well-being. Accompanying dose-dependent increases in systolic blood pressure and respiratory rate were found, suggesting that the lower doses of naloxone utilized in previous clinical studies were not sufficient to block the endogenous opioid system. CSF opioid activity in psychiatric patients and normals was measured using a sensitive radioreceptor assay developed by the authors. Results suggest diminished endogenous opioid system activity in some schizophrenics, and a relationship between opioid activity and state change in manic-depressive illness and anorexia nervosa. A complex but consistently observed relationship between ratings of anxiety and CSF opioid activity in normals and patients is consistent with basic science and clinical data suggesting interactions between CNS noradrenergic and opioid systems. General surgery was used as a strategy for studying the relationship of the endogenous opioid system to stress in humans; robust increases in levels of plasma beta-endorphin immunoreactivity accompanying surgical stress and an inverse relationship between patient levels of plasma beta-endorphin immunoreactivity and postoperative analgesic requirement were observed. These data support the involvement of the endogenous opioid system in the human stress response and suggest that hormonal stress response and endogenous opioid system activity may relate to human endogenous analgesic mechanisms.

Adolescent↗