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Biomedical subjects

L J Fitten

Publications and source records attributed to L J Fitten.

15 recordsLinked to original sources
PubMed1992

SPECT brain imaging in Alzheimer's disease during treatment with oral tetrahydroaminoacridine and lecithin.

Quantitative SPECT brain imaging was performed in five normal subjects and in six ambulatory patients with Alzheimer's disease before the initiation of treatment with tetrahydroaminoacridine (THA) and lecithin. Imaging data were acquired with a single-head SPECT camera and a high-resolution collimator after the intravenous injection of 5 mCi of (p,5n) I-123 IMP. Uptake per pixel in 28 regions of interest in the transverse projection of each study was normalized to uptake per pixel in the cerebellum. Perfusion in the patients with Alzheimer's disease was decreased compared with that of the subjects. Perfusion was decreased greater than 2 SD below the mean in the posterior parietal cortex of 5/6 patients, in the temporal cortex of 3/6 patients, and in the frontal cortex of 2/6 patients with Alzheimer's disease. SPECT imaging was repeated in the six patients after initial titration to peak therapy with oral THA (75 to 200mg per day). The same abnormalities were again seen in the same patients. No dramatic clinical or behavioral change in cerebral perfusion was observed from initial treatment of Alzheimer's disease with THA and lecithin.

Administration, Oral↗
PubMed1990

Antagonism of the hypothermic effect of clozapine in mice by centrally-active alpha 2-adrenergic antagonists and alpha 1-adrenergic agonists.

Hypothermia induced by either clozapine or clonidine in mice was blocked by the alpha 2-adrenergic antagonists yohimbine, idazoxan, CH-38083, SKF 86466, and L-657,743. These effects were dose related, and the ID50 values for inhibition of clozapine- or clonidine-induced hypothermia were fairly comparable. The order of potency for blocking clonidine-induced hypothermia was: L-657,743 greater than CH-38083 greater than yohimbine greater than idazoxan greater than SKF 86466. A very similar blockade hierarchy for clozapine-induced hypothermia was observed, with the order of the two most effective compounds being reversed. Hypothermia induced by either compound was not blocked by the peripherally-acting, selective alpha 2-adrenergic antagonist, L-659,066, indicating that blockade by the other compounds occurred centrally. The centrally-acting, alpha 1-adrenergic agonists St 587, cirazoline, and SKF 89748 were very effective in blocking the response to clozapine, but ineffective in antagonizing clonidine-induced hypothermia. The ED50 values for the blockade of this response to clozapine, however, did not correlate with their reported potencies in stimulating either peripheral or central alpha 1-adrenergic receptors. This indicates that clozapine-induced hypothermia in mice is not a suitable model for evaluating the properties of central alpha 1-adrenergic compounds. Moreover, since the clonidine-induced hypothermia is not influenced by alpha 1-adrenergic agonists, this paradigm is preferable to clozapine-induced hypothermia in the assessment of alpha 2-adrenergic antagonism The ability of alpha 2-adrenergic antagonists to block clozapine-induced hypothermia may result from the central overflow of norepinephrine, which is known to be brought about by this group of compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1990

Effect of BMY 21502 on acquisition of shape discrimination and memory retention in monkey.

BMY 21502 is a novel pyrrolidinone nootropic with demonstrated ability to reverse electroconvulsively induced amnesia in rodents. We administered BMY 21502 intramuscularly to four monkeys (Macaca radiata) during testing using two separate paradigms. The first test involved the acquisition of a visual shape discrimination task where each monkey learned to select the correct lighted panel. In the second task, memory retention was tested by having the monkeys select and press the correct lighted panel using a delayed matching-to-sample procedure. A dose-response relationship was established for the acquisition of shape discrimination for each monkey. Two performance-enhancing doses in the visual discrimination task were then employed to test for effects on memory retention at different delay intervals in the delayed-matching-to-sample task. Results indicate that BMY 21502, when administered over a wide dose range, enhanced acquisition of shape discrimination in three of four monkeys when combined drug scores were compared to vehicle-only scores (p less than 0.02). However, BMY 21502 produced no significant improvement in memory retention at any of seven different delay intervals when low-dose and high-dose scores for the three responding monkeys were compared to vehicle-only scores.

Animals↗
PubMed1990

Assessing treatment decision-making capacity in elderly nursing home residents.

Clinicians usually employ indirect measures of cognitive and physical function in order to assess medical decision-making capacity. We tested a reference group of well elderly (Mini-Mental State Exam [MMSE] score = 29.1 +/- 0.8, mean +/- SD), for their understanding of three increasingly complex, hypothetical treatment situations or "vignettes"--use of a hypnotic, need for thoracocentesis, and desire for CPR. From this, we have developed a more direct, Guttman-like assessment of decision-making capacity. Of 51 Veterans Affairs nursing home residents (MMSE score = 22.4 +/- 6.9), only 33.3% demonstrated intact decision-making capacity by this method, whereas 77% were felt by their primary physicians to be capable of giving consent for oral surgery; 37.3% had very impaired decision-making capacity; and 29.4% were intermediate in this ability. Judged against our more direct assessment of decision-making capacity, primary physicians' judgment of capacity for consent was 31% to 39% sensitive in identifying impaired decision-making and the MMSE was 53% to 63% sensitive. These measures were 100% and 82% to 83% specific in identifying intact decision-making capacity, respectively. We conclude that (1) more directly assessed decision-making capacity varies noticeably among elderly nursing home residents and correlates in only limited fashion with frequently used cognitive screening methods; and (2) cognitive screening tests underestimate the prevalence of impaired decision-making capacity in this population. For informed consent and advance directives, our study suggests that decision-making capacity should be directly, rather than indirectly, assessed.

Activities of Daily Living↗
PubMed1990

Impact of medical hospitalization on treatment decision-making capacity in the elderly.

A growing population of hospitalized elderly will need to make an increasing number of treatment decisions. No generally accepted criteria currently exist to assess the decision-making capacity of these elders. In this study, three hypothetical clinical vignettes were developed to assess treatment decision-making capacity in 25 presumably competent, medically ill, nondistressed, hospitalized elders and 25 healthy, age- and education-matched controls. The patients' understanding of the vignettes was evaluated and compared with their understanding of a standard consent form; with their performance on a mini-mental state examination; and with physician judgements about their decisional capacity. Vignette results indicate a significant difference between study and control groups in understanding of key treatment issues. Healthy controls demonstrated a better understanding of these issues. Twenty-eight percent of the patients had significant decisional impairments by vignette assessment but were not identified by mental status scores or physician judgments. Results suggest that presumably competent, medically ill elders may be at risk for developing decisional impairments during hospitalization for acute illness. Obtaining informed consent directly from many of these patients may not be feasible.

Aged↗
PubMed1989

Depression.

Explore the source record for details and available documents.

Aged↗
PubMed1989

Quantitative iodine-123 IMP imaging of brain perfusion in schizophrenia.

Decreased perfusion in the frontal lobes of patients with chronic schizophrenia has been reported by multiple observes using a variety of techniques. Other observers have been unable to confirm this finding using similar techniques. In this study quantitative single photon emission computed tomography brain imaging was performed using p,5n [123I]IMP in five normal subjects and ten chronically medicated patients with schizophrenia. The acquisition data were preprocessed with an image dependent Metz filter and reconstructed using a ramp filtered back projection technique. The uptake in each of 50 regions of interest in each subject was normalized to the uptake in the cerebellum. There were no significant confirmed differences in the comparable ratios of normal subjects and patients with schizophrenia even at the p = 0.15 level. "Hypofrontality" was not observed.

Adult↗
PubMed1987

Long-term oral administration of memory-enhancing doses of tacrine in mice: a study of potential toxicity and side effects.

Recently, tacrine (1, 2, 3, 4-tetrahydro-9-aminoacridine; THA; TAC) has received international attention as an oral agent capable of relieving some of the cognitive symptoms accompanying Alzheimer's disease (AD). When given acutely and parenterally (by injection), tacrine has also enhanced memory retention in animals and man. This study evaluates the clinical potential of this agent by assessing toxicity and major side effects of a memory-enhancing dose of tacrine in mice. Groups of mice received either tacrine or vehicle (placebo) orally for 4 to 6 months. A lack of toxicity after this prolonged treatment with TAC was indicated by: (a) no significant impairment on a battery of behavioral toxicity tests; (b) improved memory retention; (c) a significant but only slight elevation of ornithine transcarbamylase activity in blood serum; (d) no abnormality as revealed with light microscopy of liver tissue; and (e) no gross organ pathology in visceral organs.

Administration, Oral↗
PubMed1985

L-tryptophan as a hypnotic in special patients.

The authors briefly review prevalence and current treatment trends of sleep disorders in the elderly, underlining the need for the development of a more suitable hypnotic for this population. The use of L-tryptophan (LT) as a physiologic hypnotic in aged responders is considered and the hypnotic effect of 1- to 4-g bedtime doses on ten male inpatients and outpatients aged 30 to 72 years is evaluated. Results suggest a dramatic and sustained relief of insomnia for 3 weeks in 30 per cent of the patients and the absence of side effects in 90 per cent of those who took the agent. The authors conclude that despite its long therapeutic history, L-tryptophan has not been more successful because only a minority of humans appear to be responsive to its hypnotic actions. They point to the need to replicate their current preliminary observations in a larger controlled geriatric population and to delineate biochemical characteristics of LT responders in order to increase LT sensitivity in some patients and convert nonresponders to responders.

Adult↗
PubMedDate not supplied

Oral tacrine administration in middle-aged monkeys: effects on discrimination learning.

We studied the effect of chronic, oral administration of 1,2,3,4 tetrahydro-9-aminoacridine (THA), an anticholinesterase, on the acquisition of a color discrimination task in five monkeys (Macaca radiata), aged 13-19 years. A two-phase experiment was performed: initially, one animal was used and served as his own control in a multiple dose, crossover, placebo controlled trial, designed to establish a dose-response curve and an optimal dose range based on THA serum concentrations. Thereafter, four monkeys were given the optimal dose of THA (5.0 mg/day) determined previously while learning up to four color pair discriminations. They also learned up to four other color pair discriminations while on placebo. Two monkeys received THA first, then placebo; the others received placebo first, then THA. No order effects were noted. When combined scores for THA tests were compared to their placebo scores, the difference was significant at p less than 0.01 with all four THA treated monkeys requiring fewer trials to reach learning criterion. These results indicate that THA has a significantly positive effect on the acquisition of a color discrimination task.

Administration, Oral↗
PubMedDate not supplied

Quantitative EEG during a double-blind trial of THA and lecithin in patients with Alzheimer's disease.

Quantitative electroencephalography (EEG) was performed on eight of ten Alzheimer patients in a double-blind, inpatient-outpatient tetrahydroaminoacridine (THA) and lecithin trial. Neuropsychological measures were related to EEG activity. Patient baseline dominant parietal rhythms (DPRs) and power spectral distributions differed significantly from controls. Severity of cognitive impairment was related to the degree of parietal slowing. Inpatient THA treatment resulted in increased DPR frequency in six of eight patients. Four of eight inpatients demonstrated reduced power in the delta and theta bands. During the outpatient long-term treatment phase, six of the patients were able to continue. Three of these improved significantly on tests of cognition. Two of these improved patients demonstrated DPRs with increased frequency. One of these patients also showed a decrease in slow-wave activity. Thus, THA may accelerate DPRs while reducing power in the slower EEG bands. However, there appears to be only a tentative coupling between individual quantitative EEG measures and cognitive performance associated with THA administration.

Aged↗