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Biomedical subjects

K A Frey

Publications and source records attributed to K A Frey.

At least 109 records · Page 6Linked to original sources

Demonstration of prosthetic activation of central auditory pathways using [14C]-2-deoxyglucose.

The cochlear prosthesis is not applicable to patients who lack an implantable cochlea or an intact vestibulocochlear nerve. Direct electrical stimulation of the cochlear nucleus (CN) of the brain stem might provide a method for auditory rehabilitation of these patients. A penetrating CN electrode has been developed and tissue tolerance to this device demonstrated. This study was undertaken to evaluate metabolic activation of central nervous system (CNS) auditory tracts produced by such implants. Regional cerebral glucose use resulting from CN stimulation was estimated in a series of chronically implanted guinea pigs with the use of [14C]-2-deoxyglucose (2-DG). Enhanced 2-DG uptake was observed in structures of the auditory tract. The activation of central auditory structures achieved with CN stimulation was similar to that produced by acoustic stimulation and by electrical stimulation of the modiolar portion of the auditory nerve in control groups. An interesting banding pattern was observed in the inferior colliculus following CN stimulation, as previously described with acoustic stimulation. This study demonstrates that functional metabolic activation of central auditory pathways can be achieved with a penetrating CNS auditory prosthesis.

Animals↗

Thalamic, brainstem, and cerebellar glucose metabolism in the hemiplegic monkey.

Unilateral ablation of cerebral cortical areas 4 and 6 of Brodmann in the macaque monkey results in a contralateral hemiplegia that resolves partially with time. During the phase of dense hemiplegia, local cerebral metabolic rate for glucose (1CMRG1c) is decreased significantly in most of the thalamic nuclei ipsilateral to the ablation, and there are slight contralateral decreases. The lCMRGlc is reduced bilaterally in most of the brainstem nuclei and bilaterally in the deep cerebellar nuclei, but only in the contralateral cerebellar cortex. During the phase of partial motor recovery, lCMRGlc is incompletely restored in many of the thalamic nuclei ipsilateral to the ablation and completely restored in the contralateral nuclei. In the brainstem and deep cerebellar nuclei, poor to moderate recovery occurs bilaterally. Moderate recovery occurs in the contralateral cerebellar cortex. The findings demonstrate that a unilateral cerebral cortical lesion strongly affects lCMRGlc in the thalamus ipsilaterally and in the cerebellar cortex contralaterally, but in the brainstem bilaterally. Partial recovery of lCMRGlc accompanies the progressive motor recovery. The structures affected include those with direct, and also those with indirect, connections to the areas ablated.

Animals↗

Experimental hemiplegia in the monkey: basal ganglia glucose activity during recovery.

Unilateral ablation of cerebral cortical areas 4 and 6 of Brodmann in the macaque monkey results in a dense contralateral hemiplegia that recovers partially with time. During the phase of dense hemiplegia, the local cerebral metabolic rate for glucose (lCMRGlc) is decreased significantly in the caudate nucleus, putamen, globus pallidus, subthalamic nucleus, substantia nigra, and red nucleus of the hemisphere ipsilateral to the lesion. In the present study, lCMRGlc in the basal ganglia was studied during the phase of partial recovery of motor activity. lCMRGlc was partially restored, and the greatest degree of restoration occurred in structures with direct connections to the cerebral cortex (caudate nucleus, putamen, subthalamic nucleus, substantia nigra, and red nucleus). Restoration was least in structures that do not receive direct connections from the cerebral cortex (the internal and external segments of the globus pallidus). The findings support the hypothesis that corticofugal activity accounts for a substantial degree of functional recovery.

Animals↗

Assessing gestational age.

Decision making in obstetrics is based on accurate knowledge of fetal gestational age. Menstrual dating based on the last menstrual period is an accurate method for estimating gestational age. Other reliable indicators are fundal height, quickening, the date that the fundus reaches the umbilicus and the date that fetal heart tones are first auscultated. Combinations of these data approach the reliability of menstrual dating. Biochemical assays are useful in early pregnancy. Ultrasound is indispensable when the clinical situation is questionable.

Chorionic Gonadotropin↗

A sequential double-label autoradiographic method that quantifies altered rates of regional glucose metabolism.

An autoradiographic sequential double-label variant of the deoxyglucose method for measurement of local glucose utilization has been developed. This technique takes advantage of the short half-life of the positron emitter, 18F (t 1/2 = 110 min) relative to that of 14C. Sequential injection of [18F]fluorodeoxyglucose (FDG) and 14C-labeled FDG allows the production of two separable autoradiograms, each of which represents the same 20-micron brain slice, but under potentially different cerebral metabolic states. We have used this technique to demonstrate that ibotenic acid-lesioned rat striatum is selectively refractory to the depressing effects of barbiturate anesthesia upon brain glucose utilization. The described method has applicability to the analysis of small changes in regional cerebral metabolism in localized brain regions and represents a solution to the problem of intersubject variability inherent in conventional approaches to the deoxyglucose method.

Animals↗

Basal ganglia glucose utilization after recent precentral ablation in the monkey.

In the macaque monkey, unilateral ablation of areas 4 and 6 of Brodmann results initially in a significant decrease of glucose metabolic activity in the ipsilateral caudate nucleus, putamen, globus pallidus, substantia nigra, and subthalamic nucleus. The contralateral hemisphere shows nonsignificant but consistently decreased activity in the caudate nucleus, putamen, and globus pallidus. Cerebral blood flow is decreased in the same pattern as the glucose metabolic activity. The change in glucose metabolic activity results from loss of neurons known to project directly from the cerebral cortex to the basal ganglia and also from indirect effects (diaschisis) in basal ganglia structures that do not receive connections from the cerebral cortex.

Animals↗

Quantitative in vivo receptor binding III: Tracer kinetic modeling of muscarinic cholinergic receptor binding.

A tracer kinetic method is developed for the in vivo estimation of high-affinity radioligand binding to central nervous system receptors. Ligand is considered to exist in three brain pools corresponding to free, nonspecifically bound, and specifically bound tracer. These environments, in addition to that of intravascular tracer, are interrelated by a compartmental model of in vivo ligand distribution. A mathematical description of the model is derived, which allows determination of regional blood-brain barrier permeability, nonspecific binding, the rate of receptor-ligand association, and the rate of dissociation of bound ligand, from the time courses of arterial blood and tissue tracer concentrations. The term "free receptor density" is introduced to describe the receptor population measured by this method. The technique is applied to the in vivo determination of regional muscarinic acetylcholine receptors in the rat, with the use of [3H]scopolamine. Kinetic estimates of free muscarinic receptor density are in general agreement with binding capacities obtained from previous in vivo and in vitro equilibrium binding studies. In the striatum, however, kinetic estimates of free receptor density are less than those in the neocortex--a reversal of the rank ordering of these regions derived from equilibrium determinations. A simplified model is presented that is applicable to tracers that do not readily dissociate from specific binding sites during the experimental period. In this instance, specific tracer binding may be accurately determined by measuring tissue ligand concentration at a single time point after bolus intravenous injection, providing that regional cerebral blood flow is known. This derivation has potential clinical application, because it will permit construction of quantitative pictorial maps of regional free receptor densities in the human brain by means of positron emission tomographic imaging.

Animals↗

Quantitative in vivo receptor binding. I. Theory and application to the muscarinic cholinergic receptor.

A novel approach to in vivo receptor binding experiments is presented which allows direct quantitation of binding site densities. The method is based on an equilibrium model of tracer uptake and is designed to produce a static distribution proportional to receptor density and to minimize possible confounding influences of regional blood flow, blood-brain barrier permeability, and nonspecific binding. This technique was applied to the measurement of regional muscarinic cholinergic receptor densities in rat brain using [3H]scopolamine. Specific in vivo binding of scopolamine demonstrated saturability, a pharmacologic profile, and regional densities which are consistent with interaction of the tracer with the muscarinic receptor. Estimates of receptor density obtained with the in vivo method and in vitro measurements in homogenates were highly correlated. Furthermore, reduction in striatal muscarinic receptors following ibotenic acid lesions resulted in a significant decrease in tracer uptake in vivo, indicating that the correlation between scopolamine distribution and receptor density may be used to demonstrate pathologic conditions. We propose that the general method presented here is directly applicable to investigation of high affinity binding sites for a variety of radioligands.

Animals↗

Quantitative in vivo receptor binding. II. Autoradiographic imaging of muscarinic cholinergic receptors.

The in vivo distribution of [3H]scopolamine in rat brain following establishment of constant, saturating arterial tracer concentrations was examined with the use of quantitative autoradiography. The equilibrium drug distribution, studied 240 min after initiation of tracer infusion, was highly correlated with the regional density of muscarinic receptor sites determined in vitro in the same animals by autoradiographic analysis of [3H]quinuclidinyl benzilate binding. Brain regions of highest receptor density were generally correlated with known terminal fields of cholinergic neurons, and they demonstrated a protracted time course of in vivo labeling. An exception was noted in the basal pons, where a receptor population of high density without documented cholinergic innervation was rapidly labeled. It is suggested that synaptic muscarinic receptors are labeled slowly, as a consequence of either restricted tracer accessibility or competition between tracer and endogenous acetylcholine for available binding sites, and that the pontine receptors may be functionally distinct from those in other brain regions. The in vivo equilibrium binding technique used in the present study results in regional tissue radioligand concentrations directly proportional to receptor density and may, thus, provide a basis for receptor imaging in the human brain by means of positron emission tomography.

Animals↗

A regional metabolic contrast method for the study of brain pathology.

The use of 2-deoxyglucose for the measurement of regional cerebral glucose utilization in both animals and humans has gained widespread application. An attractive aspect of regional brain glucose metabolism is its apparent correlation with functional activity in neurons. Animal experiments suggest that this relationship is altered in brain lesions and that barbiturate anesthesia may be employed in the detection of brain regions where uncoupling of metabolism and neuronal function has occurred. A functional metabolic contrast technique is described that will permit determination of regional metabolism that is specifically attributable to neuronal activity. Areas of potential clinical application are discussed.

Animals↗

Rubber band ligation of hemorrhoids.

Hemorrhoids are frequently seen by family physicians. Prolapse and painless bleeding are the symptoms most commonly experienced by patients with internal hemorrhoids. These areas of chronically enlarged rectal tissue arise above the dentate line and are amenable to treatment by rubber band ligation. The procedure is safe and effective, and can be performed in the physician's office. Contraindications include infection, chronic liver or bowel disease, clotting disorders and significant thrombosis.

Hemorrhoids↗

Barbiturate-enhanced detection of brain lesions by carbon-14-labeled 2-deoxyglucose autoradiography.

Cerebral glucose metabolism in rats was examined 1 week after the production by ibotenic acid of unilateral striatal lesions. The incorporation of carbon-14-labeled deoxyglucose decreased within the lesion but much less than that of carbon-14-labeled glucose. Barbiturate anesthesia caused a reversal of the asymmetric striatal deoxyglucose labeling, such that the lesioned striatum retained more tracer than the contralateral side. The combined use of barbiturates and radiolabeled deoxyglucose may enhance the identification of recent brain infarction in experimental animals and in man.

Animals↗

A densitometer for quantitative autoradiography.

A low cost spot densitometer system is described. This system is useful for quantitative autoradiography of local cerebral glucose utilization, blood flow, receptor binding and other applications requiring densitometry on films. The densitometer can be used alone or interfaced to a microcomputer. The densitometer consists of a photographic enlarger, a digital multimeter, and the densitometer electronics. We have described how to construct, test and use the densitometer and how to interface the densitometer to a microcomputer. The advantages of this system are: (1) the ability to enlarge the image for accurate measurements from 'small' areas; (2) a completely unobscured image during measurement; (3) low cost and (4) ease of use.

Animals↗

Changes in [3H]muscimol binding in substantia nigra, entopeduncular nucleus, globus pallidus, and thalamus after striatal lesions as demonstrated by quantitative receptor autoradiography.

A quantitative autoradiographic technique for measuring the binding of [3H]muscimol to central nervous system GABA receptors is described using tritium-sensitive film. [3H]Muscimol binding was studied in primary and secondary striatal projection areas of rat brain following kainic acid lesions of the striatum. Seven days after the lesion, binding affinities in the striatum and its projection areas were not altered significantly. There was a loss of [3H]muscimol receptors in the striatum. Receptors increased in numbers in the ipsilateral globus pallidus (19%), entopeduncular nucleus (22%), and substantia nigra pars reticulata (38%). [3H]Muscimol binding was decreased in the ipsilateral anteroventrolateral and ventromedial (8%) thalamic nuclei. [3H]Muscimol binding in other brain areas (layer IV of the cerebral cortex, central gray, superior colliculus, and stratum moleculare of hippocampus) was not affected. The findings suggest that a loss of striatal innervation resulted in increased numbers of GABA receptors in striatal projection sites. It is further suggested that loss of inhibitory striatal inputs to neurons in the entopeduncular nucleus and substantia nigra pars reticulata may activate GABAergic projections to thalamus and thus result in decreased numbers of thalamic GABA receptors.

Animals↗

Quantitative autoradiography of [3H]muscimol binding in rat brain.

A simple quantitative autoradiographic technique for the study of neurotransmitter receptors that includes the use of a tritium-sensitive film permits saturation, kinetic, and competition studies of brain samples as small as 0.01 cubic millimeter. This technique was used to study [3H]muscimol binding in rat brain. Unilateral gamma-aminobutyric acid receptor supersensitivity was observed in the substantia nigra pars reticulata after production of localized lesions of the ipsilateral corpus striatum.

Animals↗