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Biomedical subjects

A Fisher

Publications and source records attributed to A Fisher.

At least 199 records · Page 11Linked to original sources
PubMed1987

Evaluating the visual-perceptual skills of children with cerebral palsy.

The Test of Visual-Perceptual Skills (TVPS) was used to determine if children with cerebral palsy demonstrated problems in visual perception on a motor-free visual perception test. Twenty-four children with cerebral palsy and 24 normal children, all of normal intelligence, were given the TVPS. Results showed that children with cerebral palsy attained significantly lower mean perceptual quotients than did the normal children. The TVPS appears to be a useful tool for the occupational therapist in evaluating visual perception in children with cerebral palsy.

Attention↗
PubMed1987

Body part identification in 1- to 4-year-old children.

The purpose of this study was to examine the sequence in which body parts are learned and can be identified by very young children. The 101 children tested were divided into four age groups: 1-year-olds, 2-year-olds, 3-year-olds, and 4-year-olds. The children were requested to point to 20 body parts on a doll. Analysis of the results indicated significant differences in the ability to identify body parts by age and sex. The greatest increase in scores occurred between the ages of 1 and 2 years, with girls achieving a slightly higher score in each age group. The percentage of subjects at each age who identified different body parts is presented, indicating the sequence in which body parts are learned.

Body Image↗
PubMed1987

Is alfentanil by infusion useful for sedation on the ITU?

Methods of sedation in the ITU have changed considerably over the last few years. Whereas the use of muscle relaxants to control ventilation was a frequent feature of those ITUs reviewed by Merriman, a more recent study by Gast and colleagues revealed a far greater use of narcotics and/or hypnotics, or combinations of the two. Alfentanil has many of those ideal properties needed of a sedative drug in the ITU--its use is associated with marked cardiovascular stability, it is a potent ventilatory depressant, has a high therapeutic ratio, minimal immunological or metabolic effects, and has an appropriate kinetic profile (low liposolubility, small volume of distribution, short half-life). The present paper describes the use of an infusion of alfentanil, in combination with increments of midazolam, to provide sedation and control of ventilation in patients admitted to a general ITU.

Adolescent↗
PubMed1986

Potential animal models for senile dementia of Alzheimer's type, with emphasis on AF64A-induced cholinotoxicity.

In this review we have described and critiqued several commonly used proposed animal models for SDAT. In particular, we have focussed on the AF64A-treated animal. Major pertinent neurochemical and behavioral data obtained so far with AF64A have been presented, and these effects have been compared with neurochemical and behavioral changes in the SDAT patient. We have commented on the possible mechanism(s) of action of AF64A in vivo, and have also presented some observations and speculations concerning the selectivity of action of AF64A as a specific presynaptic cholinotoxin. Much work has yet to be done with all the available animal models, including the AF64A-treated animal, before one could definitively state which one is the ideal model for SDAT. Data obtained to date with the AF64A-treated animal are nevertheless most encouraging. Despite some caveats, AF64A is a valuable neurochemical tool with which one can induce a persistent cholinergic deficiency of presynaptic origin. As with all new tools, however, one must always exercise due care to use it properly, and interpret the results obtained following its administration with caution.

Aged↗
PubMed1985

Antihistaminic properties of AF-14, an experimental quinuclidine derivative: discrimination between two histaminergic sites in both guinea-pig ileum and bladder.

AF-14 (1-aza-4-phenyltricyclo[6.2.2.0(2,7)]dodecan-5-one), a selective antimuscarinic agent, was shown to block the histamine-induced contractile response in Krebs solution in guinea-pig ileum and bladder. Careful linear regression analyses of the concentration-response relationship revealed that AF-14 antagonism consisted of two sequential and distinct phases, corresponding to an early phase and a late phase of the contractile response to histamine. In the late phase, the action of AF-14 was consistent with competitive antagonism, its pA2 (95% confidence limits) being 5.80-6.06 (ileum) and 5.66-5.80 (bladder). In the early phase, AF-14 almost completely blocked the contractile response at a concentration of 100-300 nM, which was much less than required to block the late phase or cholinergic contractions of the ileum or bladder. It is concluded that AF-14 discriminates between two histamine-sensitive sites that mediate muscle contraction in each of the two organs.

Animals↗
PubMed1985

Renal failure and the use of morphine in intensive care.

Intravenous morphine infusions were given to 20 patients in the intensive-care unit to provide sedation and analgesia. In 10 of the patients renal impairment was already present or developed during intensive care. Plasma morphine concentrations for a given dose of morphine and morphine clearance depended on renal function; dose-related plasma morphine concentrations rose as renal function deteriorated. Reduced morphine clearance leads to increased elimination half-life of the drug, and neurological impairment caused by unrecognised high concentrations of morphine could result in an incorrect diagnosis of cerebral damage in patients in intensive care.

Adult↗
PubMed1985

AF64A: an active site directed irreversible inhibitor of choline acetyltransferase.

Ethylcholine mustard aziridinium ion (AF64A, MEChMAz) has been proposed as a cholinergic neuron-specific neurotoxin. We report that in further studies on its mechanism of action incubation of the cholinergic neuroblastoma X glioma cell line, NG-108-15, with 100 microM AF64A resulted in a rapid decrease in cellular choline acetyltransferase (ChAT) activity which preceded cytotoxicity. Thus, a 60-85% decrease in ChAT activity was measured within 5 h of AF64A exposure, whereas cell lysis (measured as the release of the cytosolic enzyme lactate dehydrogenase into the medium) did not become apparent until 18 h of AF64A exposure. This led us to examine the effects of AF64A on partially purified ChAT. We report a concentration- and time-dependent inhibition of partially purified ChAT by AF64A that could not be reversed by dialysis but could be prevented by coincubation of the enzyme and AF64A with choline but not with acetyl-coenzyme A. We present kinetic evidence that choline and AF64A compete for the same site on the enzyme. In addition, thiosulfate, which inactivates the aziridinium ion, eliminated AF64A's capacity to inhibit the enzyme. AF64A also irreversibly inhibited partially purified choline kinase and acetylcholinesterase but not lactate dehydrogenase, alcohol dehydrogenase, carboxypeptidase A, or chymotrypsinogen, enzymes that do not use choline as a substrate or product. Thus, the data suggest that AF64A acts as an irreversible active site directed inhibitor of ChAT and possibly other enzymes recognizing choline.

Animals↗
PubMed1985

Ocular and ocular motor aspects of primary thalamic haemorrhage.

As part of a correlative study of the neuro-ophthalmological abnormalities in thalamic haemorrhage, we report preliminary findings in six patients with this condition diagnosed by clinical and CT brain examinations. Five patients were middle-aged and hypertensive. Two had Horner's syndrome, and three anisocoria. Three patients had prominent mesencephalic dysfunction. There was pathological confirmation of the lesion in one case. The pathogenesis of the signs of midbrain disturbance in these patients is uncertain, but may comprise pressure, traction or hypoxia, separately or in combination. There was no positive correlation between the estimated size of the demonstrated haemorrhage and the severity of the neuro-ophthalmological abnormality.

Adult↗
PubMed1984

AF64A, a cholinergic neurotoxin, selectively depletes acetylcholine in hippocampus and cortex, and produces long-term passive avoidance and radial-arm maze deficits in the rat.

The behavioral and biochemical effects of AF64A, a presynaptic cholinergic neurotoxin, were investigated. Bilateral administration of this compound into the lateral cerebral ventricles produced transient and dose-related effects on sensorimotor function and long-term impairments of cognitive behavior. Male Fischer-F344 rats dosed with either 15 or 30 nmol of AF64A reacted 29-62% faster than CSF-injected controls in a hot-plate test 14 (but not 1, 7, 21 or 28) days following dosing. The group administered 15 nmol of AF64A was also significantly more active (41%) than controls 28 days following dosing. The activity level of this group was comparable to that of controls at other times and hyperactivity was never observed in the 30 nmol group. Retention of a step-through passive avoidance task, assessed 35 days after dosing, was impaired in both the 15 and the 30 nmol groups. Their step-through latencies were significantly shorter than the control latencies, and they exhibited more partial entries during the 24-h retention test. Radial-arm maze performance, measured 60-80 days following treatment, was markedly impaired in the treated groups. Animals treated with AF64A made fewer correct responses in their first 8 choices, required more total selections to complete the task, and had an altered pattern of spatial responding in the maze. The neurochemical changes produced by AF64A, determined 120 days after dosing, were specific to the cholinergic system and consisted of decreases of ACh in both the hippocampus (15 and 30 nmol groups) and the frontal cortex (30 nmol group). The concentrations of catecholamines, indoleamines, their metabolites and choline in various brain regions were not affected by AF64A. Furthermore, histological analysis revealed that the doses of AF64A used in the present study did not damage the hippocampus, the fimbria-fornix, the septum or the caudate nucleus. These data support the contention that cholinergic processes in the hippocampus and/or frontal cortex play an important role in learning and memory processes. Furthermore, based upon the behavioral and biochemical data presented, it is suggested that AF64A could be a useful pharmacological tool for examining the neurobiological substrates of putative cholinergic disorders such as senile dementia of the Alzheimer's type.

Acetylcholine↗
PubMed1984

Possible mechanisms involved in the presynaptic cholinotoxicity due to ethylcholine aziridinium (AF64A) in vivo.

AF64A is a toxin which can diminish irreversibly cholinergic transmission in vivo (1, 2). Disruption of neurotransmitter function in vivo is specific to the cholinergic system when AF64A is administered in nanomolar quantities (3, 4). The mechanisms involved appear to be mediated presynaptically (g). The neurochemical and behavioral consequences of AF64A administration are reminiscent of similar measures in patients with Alzheimer's disease (5, 6). Consequently, we have suggested tentatively that the AF64A treated animal may be explored as a potential animal model of this debilitating disease state (7). In this report we provide a brief overview of our recent findings using this compound in vivo, attempt to correlate these findings with those of others with similar aziridinium agnts in vitro, and propose a possible mechanism of action of AF64A in vivo, based on recent observations made in our laboratories.

Acetylcholine↗
PubMed1984

Two pools of beta-endorphin-like immunoreactivity in blood: plasma and erythrocytes.

While attempting to delineate the reason for the reported extreme variability of beta-endorphin-like immunoreactivity (beta-ir) in human plasma (eg., nondetectable to 1 ng/ml) by standard radioimmunoassay, we noted that a substantial portion of circulating beta-ir was associated with erythrocytes. That erythrocyte associated beta-ir is authentic beta-endorphin (beta-EP) was confirmed by high performance liquid chromatography (HPLC). Analysis of blood samples from rabbits, rats and mice revealed the presence of beta-ir in erythrocytes from these species as well. These results suggest that there are two pools of beta-endorphin-like immunoreactivity in blood: plasma and erythrocytes.

Animals↗
PubMed1984

Selective cholinergic neurotoxin: AF64A's effects in rat striatum.

The selective neurotoxic effects of the aziridinium ion of ethylcholine (AF64A) have been examined after stereotaxic injection into the rat striatum. In a dose-response study (2-26 nmol), 8 nmol caused a 46% decrease in striatal choline acetyltransferase (CAT) activity with minimal effects on the activities of glutamate decarboxylase (GAD) and tyrosine hydroxylase (TH) at 7 days. Maximal CAT reductions of 78-82% occurred with doses of 16-26 nmol which also caused dose-related decreases in GAD and TH activities that paralleled the progressive decrements in CAT. A time course study with 8 nmol indicated a rapid 20% reduction of CAT activity by 12 h and an additional gradual fall of 20% over the next week; TH and GAD activities were not significantly reduced. The selective inhibition of CAT activity persisted for at least 3 months. Histological examination of Nissl stained sections revealed an area of nonspecific damage at the injection site with an abrupt border surrounded by apparently normal striatal neuropil; however; neuronal perikarya staining intensely for acetylcholinesterase were not reduced. These preliminary findings strongly suggest that AF64A has selective neurotoxic effects against striatal cholinergic neurons while relatively sparing striatal GABAergic intrinsic neurons or dopaminergic afferents.

Animals↗
PubMed1984

Neuroleptic malignant syndrome.

Three cases of the neuroleptic malignant syndrome, which complicated treatment with haloperidol, fluphenazine and, in one case, with several drugs, are described. All three patients recovered and, in two, levodopa appeared to modify the course of the condition. In one patient, myoclonus was present and has persisted. The pharmacological mechanisms involved in this syndrome are discussed.

Antipsychotic Agents↗