Biomedical subjects

K L Davis

Publications and source records attributed to K L Davis.

At least 271 records · Page 15Linked to original sources

PubMed1985

Plasma homovanillic acid concentration and the severity of schizophrenic illness.

Concentrations of plasma homovanillic acid before treatment were highly correlated with global severity of illness in schizophrenic patients, both before and after treatment. In contrast, a fixed dose of haloperidol did not affect those concentrations. Thus, in patients with a diagnosis of schizophrenia, plasma homovanillic acid may reflect the severity of illness, but not be influenced by short-term pharmacological perturbations by neuroleptics.

Adult↗

PubMed1985

Depression and immunity. Lymphocyte function in ambulatory depressed patients, hospitalized schizophrenic patients, and patients hospitalized for herniorrhaphy.

Mitogen-induced lymphocyte stimulation responses in ambulatory patients with major depressive disorder did not differ from those of matched controls. Lymphocyte responses in hospitalized schizophrenic patients and in patients hospitalized for elective herniorrhaphy similarly did not differ from responses of controls. The number of peripheral-blood T cells was decreased among the ambulatory depressed patients but not in the schizophrenic patients. These findings, together with previously reported decreased lymphocyte function in hospitalized depressed patients, suggest that decreased lymphocyte function is associated specifically with depression and not related to hospital effects or nonspecifically to other psychiatric disorders. The results also suggest that altered immunity in depression may be related to severity of depressive symptoms.

Adult↗

PubMed1985

Evaluating prolactin response to dopamine agonists in schizophrenia. Methodological problems.

Serum prolactin (PRL) level was assessed after challenges with apomorphine hydrochloride, saline, dopamine hydrochloride, or levodopa-carbidopa (Sinemet) in 19 control and 38 chronic schizophrenic subjects. Baseline PRL level varied inversely with age. High correlations existed between baseline PRL level and any subsequent absolute measure of PRL after administration of a dopamine agonist or placebo. Percent decrease was not a function of baseline concentrations and was therefore the only independent measure of drug response. Baseline PRL level was generally lower during exacerbation than remission in patients studied during two states of illness. Percent PRL level decrease after apomorphine administration was significantly greater in normal subjects than in schizophrenics. Correction of apomorphine responses for corresponding placebo (saline) values abolished differences between groups. Prolactin responses after dopamine or levodopa-carbidopa did not differ; however, placebo correction was not possible.

Acute Disease↗

PubMed1985

Cholinergic modulation of memory in rats.

Central cholinergic systems have long been implicated in the modulation of learning and memory processes in animals and man. Drugs that affect the central cholinergic system have been found either to enhance or to hinder performance in tests of learning and memory. Few studies have evaluated the effects of different cholinergic drugs within a single experimental paradigm and with a relatively wide dose range. The studies reported here investigated the effects of cholinergic drugs with diverse modes of action on the retention of a passive avoidance response. Physostigmine, arecoline, oxotremorine, nicotine, and 4-aminopyridine were administered IP immediately following the acquisition of a one-trial passive avoidance task. All of the drugs were found to enhance 72-h retention of passive avoidance; however, the effective doses were different for each of the drugs studied.

4-Aminopyridine↗

PubMed1985

Effect of chronic haloperidol and quinacrine coadministration on striatal HVA levels and stereotypic behaviors in response to apomorphine in the rat.

The effects of chronic administration of quinacrine, a phospholipase A2 inhibitor, on striatal homovanillic acid (HVA) levels and behavioral sensitivity to challenge with a dopamine agonist were examined in rats. Moreover, the ability of chronic phospholipase A2 inhibition to modulate the behavioral supersensitivity and striatal HVA reduction induced by chronic haloperidol administration was also examined. Daily intraperitoneal injection of quinacrine resulted in a significant reduction of striatal HVA levels. Coadministration of haloperidol with quinacrine in this paradigm caused a more profound reduction of striatal HVA levels than either drug administered alone. That this effect of combined administration is not simply due to postsynaptic effects of quinacrine on dopamine receptor sensitivity is suggested by the fact that behavioral supersensitivity was not induced by quinacrine alone nor was the behavioral supersensitivity induced by the quinacrine-haloperidol combination greater than that induced by chronic haloperidol administration alone. There were no effects of any treatment condition on striatal levels of serotonin (5-HT) or 5-hydroxyindoleacetic acid (5-HIAA). These data implicate phospholipase A2 activity in the regulation of dopaminergic transmission.

Animals↗

PubMed1985

Red blood cell choline. I: Choline in Alzheimer's disease.

Seventeen drug-free patients with Alzheimer's disease (AD) and 15 normal elderly controls, of which 13 age- and sex-matched pairs were included, participated in a study of red blood cell (RBC) and plasma choline. Mean values for RBC choline, plasma choline, and the ratio of RBC/plasma choline did not differ between the AD and control groups. Degree of dementia did not correlate with any blood choline measure. A correlation was found between age and RBC choline (r = 0.57; p less than or equal to 0.01) and the RBC/plasma choline ratio (r = 0.56; p less than or equal to 0.03) in normals, but not in AD patients. RBC choline correlated with plasma choline in AD patients only (r = 0.46, p less than or equal to 0.03). These results do not support the use of RBC and plasma choline concentrations as either a diagnostic tool to identify AD patients or an antemortem index of the cholinergic deficit in brains of patients with Alzheimer's disease.

Aged↗

PubMed1985

Red blood cell choline. II: Kinetics in Alzheimer's disease.

The kinetic parameters of choline uptake into red blood cells from patients with Alzheimer's disease and normal elderly controls were compared. The Kd and Vmax values for choline uptake into red cells were determined based on a kinetic analysis of choline uptake at six different concentrations of labeled extracellular choline. The theoretical choline uptake, representing the initial rate of choline influx into choline-depleted red cells given the plasma choline concentration and the kinetic parameters of choline uptake, was also calculated. Alzheimer's disease patients and normal controls did not differ in any kinetic parameter of choline uptake. Kd and Vmax values for red cell choline uptake were strongly correlated among normal controls, but not among patients with Alzheimer's disease. In addition, among the patients with Alzheimer's disease, the theoretical choline uptake was strongly correlated with the severity of dementia. The possible significance of these findings in relation to altered choline metabolism in Alzheimer's disease is discussed.

Aged↗

PubMed1985

Apomorphine has no effect on plasma homovanillic acid in schizophrenic patients.

Previous experiments suggest that pharmacological perturbations of the brain dopaminergic system may be reflected by concentrations of plasma homovanillic acid. This study examined the ability of low-dose apomorphine to reduce plasma homovanillic acid concentrations in schizophrenic patients chronically treated with neuroleptics. The data suggest that apomorphine does not reduce plasma homovanillic acid in those patients.

Adult↗

PubMed1985

Clinical studies of the cholinergic deficit in Alzheimer's disease. I. Neurochemical and neuroendocrine studies.

Autopsy studies indicating that cholinergic neurons are selectively lost in patients with Alzheimer's disease (AD) and senile dementia of the Alzheimer type (SDAT) suggest that peripheral markers for central cholinergic activity would be useful in diagnosis. The present studies found that cerebrospinal fluid (CSF) concentrations of acetylcholine (ACh) correlated with the degree of cognitive impairment (r = .70) in a sample of carefully diagnosed patients with AD/SDAT, but metabolites of other neurotransmitters were not related to cognitive state; this suggests that CSF ACh may be a valid measure of cholinergic degeneration. Cortisol and growth hormone were measured in plasma samples drawn from patients and controls every 30 minutes from 2100 to 1100 hours the next day. Mean plasma cortisol concentrations were higher in patients with AD/SDAT than in controls and correlated inversely with CSF methoxy-hydroxyphenylglycol (MHPG) (r = .61) and positively with degree of cognitive impairment (r = +.53); as anticholinergic drugs suppress cortisol this finding indicates that cortisol dysregulation may be a marker for abnormalities in other neurotransmitter systems, particularly the noradrenergic system. Growth hormone secretion was not different in patients and controls but was positively correlated with CSF MHPG (r = +.63).

Acetylcholinesterase↗

PubMed1985

Clinical studies of the cholinergic deficit in Alzheimer's disease. II. Psychopharmacologic studies.

Two studies investigated the ability of physostigmine, given both intravenously and orally, to reduce symptoms of Alzheimer's disease. Intravenous physostigmine significantly and reliably enhanced memory in 13 of 16 patients tested, but the dose producing the improvement varied among patients. Oral physostigmine decreased overall symptom severity in a reliable way in seven of 12 patients tested. The extent of improvement was correlated with the increase in mean cortisol secretion produced by physostigmine, suggesting that the drug improved behavior and cognition only to the extent that it had a specific central cholinomimetic effect. There was no significant association between response to physostigmine and results of a dexamethasone suppression test and physostigmine had no effect on growth hormone secretion.

Administration, Oral↗

PubMed1985

Oral physostigmine treatment of patients with Alzheimer's disease.

Twelve patients with Alzheimer's disease received 0.0, 0.5, 1.0, 1.5, and 2.0 mg of oral physostigmine every 2 hours for 3-5 days; symptoms after each dose were assessed with the Alzheimer's Disease Assessment Scale. Placebo and the dose associated with the least severe symptoms were then readministered for 3-5 days each. Of the 10 patients who completed the study, three showed clinically significant improvement on the highest physostigmine dose in both phases, four more were marginally improved in both phases, and three had inconsistent responses to physostigmine. Cortisol measures obtained during a sleep study suggest that patients whose symptoms improved on physostigmine were those in whom oral physostigmine enhanced central cholinergic activity.

Administration, Oral↗

PubMed1985

Overview: toward a dysregulation hypothesis of depression.

The authors suggest that the activity of neurotransmitter systems in the affective disorders and related psychiatric syndromes may be better understood as a reflection of a relative failure in their regulation, rather than as simple increases or decreases in their activity. A model organized around the concept of "dysregulation" posits that persistent impairment in one or more neurotransmitter homeostatic regulatory mechanisms confers a trait vulnerability to unstable or erratic neurotransmitter output. Evidence from clinical and animal model studies for dysregulation of the noradrenergic system in depression is examined with respect to criteria generated by such a general model, and a specific configuration of noradrenergic dysregulation in some forms of depression is proposed.

Animals↗

PubMed1985

Psychiatric illness in first-degree relatives of patients with paranoid psychosis, schizophrenia and medical illness.

This study examines the respective morbid risk for psychiatric illness determined by the family history method in the first-degree relatives of medical controls and patients with delusional disorder (paranoid psychosis) and schizophrenia. The morbid risk for schizophrenia and schizoid-schizotypal personality disorder was significantly greater in the relatives of the schizophrenic patients than in those of the delusional disorder or medical control patients, but no difference in the risk for affective illness or alcoholism was found in the three groups of relatives. Paranoid personality disorder was significantly more common in the relatives of the delusional disorder patients than in those of the medical controls. These results support the familial independence of delusional disorder and schizophrenia.

Adult↗

PubMed1984

Brain uptake indices of guanidine and 4-aminopyridine.

A deficiency of central neural transmission mediated by acetylcholine (ACh) is implicated in the etiopathology of Alzheimer's disease. The appreciation of this neurochemical deficit has led to treatment strategies designed to facilitate central cholinergic transmission (1). A major limitation of current clinical studies is the availability of centrally-effective, long-acting cholinomimetic agents. This situation has led to the search for such agents.

4-Aminopyridine↗

PubMed1984

Genetic control of apomorphine-induced climbing behavior in two inbred mouse strains.

Over a wide dose range (1-32 mg/kg), apomorphine-induced climbing behavior was significantly greater in the AKR/J than in the DBA/2J inbred mouse strain. A similar difference was found when apomorphine-induced stereotypy was examined. A cross-fostering study demonstrated that the strain difference in apomorphine-induced climbing behavior did not result from differences in post-natal rearing environment. After apomorphine administration, brain levels of the drug were similar in the two strains indicating that the difference in behavioral response to apomorphine in the two strains was not due to differences in metabolism or distribution of the drug. The climbing response to apomorphine was examined in the F1 cross of the two strains (AKD2F1/J) and in 10 AKXD recombinant inbred strains. Results suggested that the trait was partially dominant and not X-linked; furthermore, a few and possibly one locus was responsible for the differences in apomorphine-induced climbing behavior observed in the AKR/J and DBA/2J mice.

Animals↗

PubMed1984

Lymphocyte function in major depressive disorder.

Lymphocyte stimulation by phytohemagglutinin, concanavalin A, and pokeweed mitogen was significantly lower in a group of hospitalized depressed patients than in matched controls. The absolute number of T and B cells was lower in the depressed group, but the percentage of these cell types did not differ between the groups. These findings may be related to the altered neuroendocrine function found in patients with depressive disorders.

Adult↗

PubMed1984

Apomorphine and schizophrenia. Treatment, CSF, and neuroendocrine responses.

Previous studies have variably reported the efficacy of apomorphine in treatment of schizophrenia and tardive dyskinesia. Stimulation of dopamine neuron autoreceptors is the presumed mode of action. Low-dose apomorphine (0.75 mg subcutaneously) and placebo were administered to 25 male schizophrenics to evaluate the drug's effect on psychotic and tardive dyskinetic symptoms. No significant improvement or deterioration was seen. Concomitant measurements of plasma prolactin and growth hormone levels and CSF homovanillic acid level indicated that the dose used was centrally active. These results indicate that an active though nonsedating dose of apomorphine does not ameliorate symptoms of schizophrenia or tardive dyskinesia.

Adult↗

PubMed1984

Positive and negative symptoms in schizophrenia.

Negative and positive symptoms were determined for 46 drug-free patients who met Research Diagnostic Criteria (RDC) and/or Feighner criteria for schizophrenia. A modified version of the Scale for the Assessment of Negative Symptoms (SANS) was completed for each patient based on items from the Schedule for Affective Disorders and Schizophrenia (SADS) and other scales. Positive symptoms were scored from the SADS as well as from the following four diagnostic systems: RDC, Schneider's first-rank symptoms, the 12-point Flexible system, and Langfeldt's criteria for poor prognosis schizophrenia. For all patients, there was no correlation of negative symptoms and positive symptoms defined by any diagnostic system. Within the paranoid and undifferentiated subtypes, there was a positive correlation of positive and negative symptoms. Patients moving from stable to exacerbated states had an increase in both positive and negative symptoms, and patients with a poor history of treatment response had both more positive and more negative symptoms than responsive patients in a stable state. These results do not support the view that subgroups of patients have predominantly either negative or positive symptoms.

Adult↗