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Biomedical subjects

L I Wolfson

Publications and source records attributed to L I Wolfson.

At least 19 recordsLinked to original sources

Antemortem diagnosis of diffuse Lewy body disease.

Using the presence of widespread cortical Lewy bodies (LB) as the pathologic criteria of diffuse Lewy body disease (DLBD), we describe serial neurologic and mental status examinations in 6 patients with DLBD, 3 patients with Alzheimer's disease (AD), and 1 patient with Parkinson's disease (PD). The 6 patients with DLBD included 3 with neocortical neurofibrillary tangles (NFT) consistent with coincident AD. Most patients with DLBD had gait impairment concurrent with mild to moderate dementia. Abnormalities of tone or resting tremor were also prominent early symptoms in the subjects with DLBD, but not AD. Patients with DLBD frequently had abnormal EEGs with background posterior slowing and a frontally dominant burst pattern at the time of mild to moderate dementia. Agitation, hallucinations, and delusions were frequent early symptoms in DLBD patients. Patients with DLBD without concomitant AD had numerous Alz-50 negative cortical plaques. Patients with DLBD have a distinct clinical syndrome that can be differentiated from AD. Pathologic features, including the absence of Alz-50 immunoreactivity, also differentiate DLBD from AD.

Aged

Functional neuroanatomic mapping of the rat striatum: regional differences in glucose utilization in normal controls and after treatment with apomorphine.

Glucose utilization was measured in 5 regions of rat striatum within four anterior-posterior levels. Areas of minimal and maximal glucose utilization were identified. Density-window image analysis was used to quantify areas of minimal and maximal glucose utilization, which were also apparent upon close visual inspection. In a normal control group, there were substantial regional variations in striatal glucose utilization (e.g. dorsal vs ventral; dorsomedial vs dorsolateral), revealing a detailed pattern, previously unavailable, which served as a baseline to study the effect of systemic apomorphine. The highest levels of glucose utilization were in small islands 0.01-0.25 mm2, and in what appeared to be dense clusters of islands that formed larger zones. Apomorphine treatment decreased glucose utilization in dorsomedial regions, increased it in a ventromedial region, and did not change it in others. The findings emphasize the importance of regional analysis of striatum in functional and physiological studies, and provide a new baseline for analyses of striatal glucose utilization in studies of development and aging, drug effects, external stimuli, and rat models of movement disorders.

Animals

The relationship of knee and ankle weakness to falls in nursing home residents: an isokinetic study.

The strength of the knees and ankles of a group of nursing home residents with a history of falls was compared to age-matched controls. Peak torque (PT) and power (POW) were recorded at two limb velocities (60 degrees/s and 120 degrees/s) on a Cybex II Isokinetic dynamometer for four muscle groups: knee extensors, knee flexors, ankle plantar flexors and ankle dorsiflexors. The PT and POW of fallers were significantly decreased for all four muscle groups in comparison to controls, with the ankles showing the greatest decrements. Although POW in fallers was significantly lower at the higher velocity in both joints, the decrease was most prominent in the ankles. Dorsiflexion POW production in fallers was the most affected of all the motions (7.5 times less than the control value). At the higher, more functional limb velocities, ankle weakness particularly involving the dorsiflexors appears to be an important factor underlying poor balance.

Accidental Falls

Stressing the postural response. A quantitative method for testing balance.

Using a series of graded destabilizing forces, we have developed a simple quantitative test of the postural response: the Postural Stress Test (PST). Suitable for widespread testing of elderly subjects, the test evaluates the subject's ability to avoid a fall as well as the appropriateness of the response. We have determined that by comparison with young subjects, the elderly controls have compromised although functionally effective balance. On the other hand, the balance response was severely compromised in half of the individuals with a history of falls. Experience with the Postural Stress Test suggests it will predict those elderly individuals with a tendency to fall as well as provide a simple mechanism for studying the balance response in the elderly.

Accidental Falls

Serotonin models of myoclonus in the guinea pig and rat.

Myoclonus could not be induced in rats with either L-5-HTP alone or hypoxia. Following amine depletion or destruction of the serotonin neurons with 5,7-DHT, myoclonus appeared as part of a complex serotonergic behavioral syndrome induced by serotonin agonists. On the other hand, in the guinea pig, L-5-HTP induces a pure myoclonic syndrome in a dose-dependent fashion. Myoclonus also was induced by injection of serotonin into the dorsal pons of the guinea pig. This is additional evidence confirming the importance of the brainstem structures in the L-5-HTP guinea pig model of myoclonus. Deoxyglucose (DG) autoradiography in guinea pigs following systemic L-5-HTP administration demonstrated increased glucose metabolism within thalamic and third nerve nuclei, with decreased metabolism in the cortex, and the molecular layer of the hippocampus. Since serotonin is an inhibitory transmitter, we hypothesize that the decreases observed in cortex may be the result of direct serotonergic inhibition, whereas the increases observed in the thalamus probably represent indirect effects via polysynaptic pathways.

5-Hydroxytryptophan

Alterations of regional cerebral blood flow and oxygen metabolism in Parkinson's disease.

Regional cerebral blood flow (rCBF) and oxygen metabolism (rCMRO2) were determined in six normals, six unilateral Parkinson's disease (PD) patients, and eight bilateral PD patients. In the unilateral patients, rCBF and rCMRO2 in the basal ganglia contralateral to the symptomatic limbs was 13% higher than on the other side (p less than 0.01); in the frontal cortex it was 8% lower than the other side, suggesting abnormal neuronal function in both regions. The bilateral PD patients had a widespread decrease (20%) in rCBF unaccompanied by comparable changes in rCMRO2, suggesting vasoconstriction due to loss of dopaminergic innervation of blood vessels in more advanced PD patients.

Cerebrovascular Circulation

Gait and balance in the elderly. Two functional capacities that link sensory and motor ability to falls.

Neuromuscular function, which underlies efficient gait and balance, deteriorates with age and disease. A review of the literature and of data from the current study suggests the presence of poor gait and balance in elderly individuals who have a history of multiple falls. The tests of gait and balance are simple to perform and therefore may be widely applicable in evaluating individuals at risk of falls. Quantitative studies of motor and sensory function, vibratory sensation, and electrophysiologic studies of nerve integrity are discussed. Deteriorating motor and sensory control mechanisms appear to play an important role in falling.

Accidents

A direct role of dopamine in the rat subthalamic nucleus and an adjacent intrapeduncular area.

The subthalamic nucleus, a clinically important component of the extrapyramidal motor system, and a lateral area extending into the peduncle contain catecholamine terminals and dopamine receptors coupled to adenylate cyclase. In addition, dopamine agonists administered in vivo enhance glucose utilization in the region. Thus, neuronal function in this region is directly affected by dopamine and dopaminergic drugs.

Adenylyl Cyclases

Juvenile parkinsonism: a patient with possible primary striatal dysfunction.

A 15-year-old boy who initially manifested dystonic features and later developed classic parkinsonism is described. Cerebrospinal fluid homovanillic acid levels were normal or slightly elevated both before and after administration of probenecid. The patient responded favorably to treatment with levodopa and carbidopa. The normal or slightly elevated cerebrospinal fluid homovanillic acid levels contrast with the low levels usually seen in adult parkinsonian patients. The data on this patient suggest direct neostriatal involvement rather than depletion of neurons of the substantia nigra. Juvenile parkinsonism may have at least two distinct pathological forms, but they have similar clinical features and a similar response to treatment.

Adolescent

Ventricular fluid homovanillic acid and 5-hydroxyindoleacetic acid concentrations in patients with movement disorders.

Ventricular fluid concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), the respective metabolites of dopamine and serotonin, were measured in 57 patients undergoing thalamotomy for relief of movement disorders. The diseases included were Parkinson disease, dystonia, cerebral palsy, multiple sclerosis, and posttraumatic or posthypoxic encephalopathy. Untreated parkinsonian patients had the lowest mean HVA level (119 ng per milliliter). Patients with multiple sclerosis or with posttraumatic or posthypoxic encephalopathy with both intellectual impairment and bilateral motor involvement had lower mean HVA levels (197 and 177 ng per milliliter, respectively) than cerebral palsy patients with bilateral motor disease (233 ng per milliliter), dystonia patients (246 ng per milliliter), or multiple sclerosis patients with normal intellect (376 ng per milliliter). The data suggest that diffuse cerebral disease may lead to diminished dopaminergic activity. Ventricular fluid 5-HIAA levels were similar in all groups of patients. Chronic cerebellar stimulation markedly increased ventricular fluid HVA and 5-HIAA levels, indicating that cerebellar stimulation affected cerebral dopaminergic and serotonergic systems.

Adult

Diminished ventricular fluid dopamine metabolites in adult-onset dystonia.

Homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), the respective metabolites of dopamine and serotonin, were measured in ventricular fluid obtained from 20 patients with torsion dystonia at the time of ventriculography prior to thalamic surgery. The patients could be divided into two distinct types of dystonia--childhood-onset and adult-onset--which were identifiable on clinical and biochemical grounds. In the 14 patients with childhood-onset dystonia, the first symptom appeared in one limb in early childhood and the disease usually progressed rapidly. In the six patients with adult-onset dystonia, the first symptom usually appeared in axial muscles after adolescence and the disease progressed slowly. Ventricular fluid HVA levels were significantly lower in the patients with adult-onset dystonia than in those with childhood-onset dystonia. The differences suggest diminished dopaminergic activity, possibly secondary to nigrostriatal dysfunction, in adult-onset dystonia.

Adolescent

Clearance of 3-methoxy-4-hydroxyphenylglycol from the cerebrospinal fluid.

The clearance of 3-methoxy-4-hydroxyphenylglycol (MHPG) from the cerebrospinal fluid of cats was studied. Both ventriculocisternal and cerebral subarachnoid perfusions demonstrated relatively high clearances that could not be blocked by probenecid. MHPG removal increased proportionally at all concentrations studied, suggesting diffusional clearance from cerebrospinal fluid. Bulk clearance accounted for only one-third of MHPG clearance from brain, and the likely mechanism of MHPG removal from the central nervous system is by diffusion to capillary blood. Differences between amine metabolites removed by mediated transport and diffusion are summarized, and it is suggested that a rapid unblockable diffusional clearance mechanism tends to make lumbar levels of MHPG a poor index of brain norepinephrine metabolism.

Animals