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Biomedical subjects

M D Yahr

Publications and source records attributed to M D Yahr.

At least 19 recordsLinked to original sources
PubMed1992

Changes in body temperature markedly affect striatal dopamine release and metabolism: an in vivo study.

Dopamine release and metabolism in the corpus striatum increased markedly when the core body temperature of anesthetized rats was increased from 35 degrees to 41 degrees C while temperatures below 34 degrees were associated with a marked attenuation of dopamine release. These observations may have clinical relevance in cases where alterations in body temperature are associated with extrapyramidal dysfunction.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Hypotension-induced vasopressin release distinguishes between pure autonomic failure and multiple system atrophy with autonomic failure.

To investigate whether activation of afferent and central baroreceptor pathways could differentiate between pure autonomic failure (PAF) and multiple system atrophy with autonomic failure (MSA), we determined the effect of upright tilt on circulating levels of vasopressin in patients with PAF and patients with MSA. We also studied 14 normal subjects, nine of whom developed acute hypotension due to vasovagal syncope. In patients with PAF and in normal subjects with vasovagal syncope, upright tilt induced marked hypotension and a pronounced increase in the plasma concentration of vasopressin (1.1 +/- 0.3 to 38.0 +/- 8.0 pmol/l in PAF and 1.0 +/- 0.2 to 27.4 +/- 7.2 pmol/l in vasovagal syncope, p less than 0.005 for both). In patients with MSA, upright tilt also elicited profound hypotension but circulating levels of vasopressin increased little (0.5 +/- 0.1 to 1.5 +/- 0.3 pmol/l, p less than 0.05). During upright tilt, the plasma concentration of norepinephrine significantly increased in normal subjects but did not increase in patients with autonomic failure. Our results indicate that afferent and central baroreceptor pathways involved in vasopressin release are normal in patients with PAF but are impaired in patients with MSA. Thus, measurement of baroreceptor-mediated vasopressin release appears to provide a clear marker to differentiate between patients with PAF and patients with MSA.

Adult↗
PubMed1992

Catechol-O-methyltransferase inhibition increases striatal L-dopa and dopamine: an in vivo study in rats.

We administered Ro 40-7592, an inhibitor of the enzyme catechol-O-methyltransferase (COMT) that crosses the blood-brain barrier, to rats and monitored extracellular catecholamine levels in the corpus striatum before and after the intraperitoneal administration of a bolus of l-dopa. Acute administration of Ro 40-7592 increased basal levels of l-dopa and dihydroxyphenylacetic acid (DOPAC) and decreased basal homovanillic acid (HVA) levels, but did not affect basal dopamine levels. In rats treated with Ro 40-7592, l-dopa administration produced a greater increase in striatal levels of l-dopa, dopamine, and DOPAC than it did in controls, while HVA formation was attenuated. We conclude that inhibition of COMT activity promotes central dopamine synthesis and release following administration of pharmacologic doses of l-dopa.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Early combination of selegiline and low-dose levodopa as initial symptomatic therapy in Parkinson's disease. Experience in 26 patients receiving combined therapy for 26 months.

Thirty-eight patients newly diagnosed as having Parkinson's disease (mean age, 57.3 years; mean Parkinson's disease duration, 2.7 years) in the earlier phase of the disease (mean Hoehn/Yahr stage, 2; mean motor scores, 11.4) were given selegiline (Deprenyl), 10 mg daily, and maintained on this drug alone until significant clinical worsening warranted the addition of low-dose levodopa (Sinemet, 25/100 three to four doses per day). Five of these patients were not yet receiving additional levodopa despite some worsening of motor scores. Of the 33 patients now taking combined therapy, seven have been followed up for 6 months or less. Twenty-four (92%) of the 26 patients taking combined therapy for a mean of 26 months (8.5 to 99 months) who have had Parkinson's disease for 6 years showed a dramatic improvement in their parkinsonism shortly after the addition of levodopa, with significant decreases in their rated motor scores, such improvement being maintained at their latest neurologic evaluation. Eighteen (75%) of these 24 patients responded to the combined selegiline/levodopa therapy with degrees of improvement equal to or greater than 50%, compared with their motor status at the start of combined therapy just before the addition of levodopa. This degree of "reversal" of parkinsonism on addition of levodopa (mean carbidopa/levodopa dose, 98/389 mg) was not observed in any of these same patients receiving selegiline alone for an average of 13.8 months. Four patients taking combined therapy developed mild, transient, abnormal involuntary movements, and end-of-dose pattern of response after more than 2 years of combined therapy (24.75 and 33.5 months, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Therapy, Combination↗
PubMed1991

Lewy bodies in parkinsonism share components with intraneuronal protein bodies of normal brains.

Histochemical characteristics of the Lewy bodies, in catecholamine neurons of 10 Parkinsonian patients, were compared to those of the spherical protein bodies, the basic protein-rich markers of catecholamine neurons in man. Special methods for proteins and lipids showed that the core of the Lewy bodies, in the neurons of the locus coeruleus and the substantia nigra, contains basic proteins and lipids normally found in the protein bodies. Acid fuchsin and the lipid-soluble fluorescent dye rhodamine B stained the entire core of the Lewy body in the parkinsonian brains and the entire sphere of the protein body in the control brains. Bromsulfophthalein, another acidic dye, which selectively binds to the enzyme gluthathione-S-transferase, had affinity only for a ring-like lamina at the outer layer of the core of the Lewy body and for the outer rim of the protein body. These results demonstrate that Lewy bodies and protein bodies contain similar macromolecular components, that is lipids and two different types of proteins, which also show similar stratification in the two structures. On the other hand, the presence in several neurons of the Parkinsonian patients, of aggregates representing transitional forms between protein bodies and Lewy bodies, indicates that abnormalities of protein bodies precede, and are somehow linked to Lewy body production.

Brain Stem↗
PubMed1991

Effect of yohimbine on brain monoamines: an in vivo study.

Following the administration of yohimbine, an alpha 2-adrenoreceptor antagonist, the levels of norepinephrine (NE), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5HIAA) increased significantly in the lateral ventricular fluid of rats. These increases were abolished when animals were pretreated with alpha-methyl-para-tyrosine or reserpine. Dopamine (DA) was not detected in ventricular fluid either before or after yohimbine administration. Yohimbine administration did, however, increase intracellular DA levels in the corpus striatum. These findings indicate that yohimbine promotes NE and DA release in the brain and suggest that it also modifies the activity of the serotonin system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Differential effect of L-threo-3,4-dihydroxyphenylserine in pure autonomic failure and multiple system atrophy with autonomic failure.

Treatment with L-threo-3,4-dihydroxyphenylserine (L-threo-dops), a synthetic precursor of norepinephrine, significantly increased upright blood pressure in patients with multiple system atrophy but had no effect on the upright blood pressure of patients with pure autonomic failure. These results suggest that the site of action of L-threo-dops is central and that its pressor effect requires intact peripheral sympathetic neurons.

Adult↗
PubMed1991

Effect of dietary protein on striatal dopamine formation following L-dopa administration: an in vivo study.

We varied the diet of rats and monitored extracellular levels of dopamine in the striatum. Following L-dopa administration, the increase in striatal dopamine levels was attenuated by 78% in rats that had consumed a high protein diet as opposed to a low protein diet. Similarly, the increase in striatal dopamine levels was attenuated by 61% in rats that had just eaten a protein-containing meal as compared to fasting animals. These findings demonstrate that dietary protein strongly affects brain dopamine formation from exogenous L-dopa.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Effect of long-term L-dopa administration on striatal extracellular dopamine release.

When L-dopa was administered acutely to rats, the increase in the extracellular level of dopamine in the corpus striatum was attenuated by 43% in animals that had received L-dopa daily for 60 days as compared with animals receiving placebo. These findings indicate that chronic treatment with L-dopa impairs striatal dopamine formation or release.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Different laws govern motor activity in sleep than in wakefulness.

A wide range of elementary and complex motor activities are known to occur during sleep, but very little is known about the basic physiologic condition of the skeletal muscle during sleep. The present study provides evidence that a minute electric random activity constitutes the basic physiologic condition of the skeletal muscles during sleep. During the NonREM stages of each sleep cycle a regression of the continuous random minute activity occurs, followed by a sudden increase of the isolated motor unit action potentials during REM sleep. Particular structural features of the anterior tibial (AT) muscle make it the most active skeletal muscle during sleep. During wakefulness, at rest, the random muscle activity disappears.

Adult↗
PubMed1990

The auditory P 300 correlates with specific cognitive deficits in Parkinson's disease.

An abnormally prolonged latency of the P 300 event-related potential has been reported in several types of dementing illnesses, including Parkinson's disease (PD). While some PD patients have dementia, a significant number of PD patients have less severe cognitive impairments. We examined the relationship between the auditory P 300 and a neuropsychological battery of 11 tasks in 43 PD patients. The quantitative relationship between the individual neuropsychological measures and the P 300 was examined using partial correlation and analysis of covariance techniques which controlled for age, education, and illness duration. The strongest correlations were between P 300 and both short-term memory and visual perception. Global cognitive deficits do not appear to relate to the abnormal P 300 responses in PD: instead, specific aspects of cognitive decline accounted for the electrophysiological abnormalities. An abnormally long or absent P 300 correlated with deficits on select cognitive tasks: those involving memory, visual perception, and abstract reasoning. The interactions between anatomical and neurochemical abnormalities in PD are discussed in light of the pattern of deficits seen in this study.

Adult↗
PubMed1990

Atrial natriuretic factor in human autonomic failure.

To investigate whether excessive circulating levels of atrial natriuretic factor (ANF) are responsible for orthostatic hypotension and nocturnal polyuria in patients with autonomic failure, we determined the circadian variation in the plasma concentration of ANF as well as the response of this peptide to changes in posture and extracellular fluid volume in patients with autonomic failure. We found that the plasma concentration of ANF was significantly lower in patients with autonomic failure than in controls. Patients with autonomic failure had a significantly higher urinary sodium excretion during the night (8 PM to 8 AM) than during the day (8 AM to 8 PM), and the plasma concentration of ANF significantly decreased during the night in these patients, indicating that high circulating levels of ANF were not the cause of the nocturnal natriuresis. Furthermore, circulating levels of ANF responded appropriately to reductions in right atrial pressure induced by head-up tilt and extracellular fluid volume changes induced by mineralocorticoid administration. These results indicate that exaggerated circulating levels of ANF are not responsible for the orthostatic hypotension or nocturnal natriuresis in patients with autonomic failure, and that appropriate regulation of ANF occurs in patients with autonomic failure.

Adult↗
PubMed1990

Visuospatial orientation in Parkinson's disease.

Visuospatial functioning in patients with Parkinson's disease was investigated using neuropsychological measures of basic visual perception, complex perceptual discrimination, and spatial orientation. Three subgroups of patients were described: (a) those with broadly impaired visuospatial abilities, (b) those with generally intact abilities, and (c) those whose performance on a task of spatial orientation was lower than their performance on a task of complex perceptual discrimination. These subgroup differences were also concordant with three other variables: age, duration of disease, and degree of dementia. It is suggested that decreases in spatial orientation functioning in Parkinson's disease may reflect the speed of progression of this disease.

Adult↗
PubMed1989

Selegiline use to prevent progression of Parkinson's disease. Experience in 22 de novo patients.

To test the hypothesis that selegiline (L-deprenyl), a selective inhibitor of B-type monoamine oxidase, can halt the natural progression of Parkinson's disease, its use in 22 naive patients (mean age, 58 years; mean Parkinson's disease duration, 2.3 years) in the early stages (1 to 2) of the disease was studied. Patients were started and maintained on a daily dose of 10 mg of selegiline, and they underwent neurologic examinations at 3-month intervals using our center's disease staging and total rated disability scores. The criterion set for disease progression was defined as either the appearance of a new objective sign and/or a definite, persistent worsening (greater than 25%) of existing signs after the initiation of the selegiline trial. Patients remained on a regimen of selegiline [corrected] for periods ranging from 7 to 84 months. At the time of their latest neurologic examination, 17 (77%) of the 22 patients had conditions that demonstrably worsened with selegiline alone at an average of 10.8 months from the start of the drug therapy. Six of these 17 patients with worsening conditions (or 27% of the original 22) eventually required the addition of levodopa with carbidopa (Sinemet) on average at 13 months from the start of selegiline therapy; they have continued, to date, taking this combination for an additional mean follow-up period of 20.7 months. Four of the original 22 patients had relatively unchanged, stable neurologic status at the time of their latest examination (average follow-up period, 11.6 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Selegiline as an adjunct to conventional levodopa therapy in Parkinson's disease. Experience with this type B monoamine oxidase inhibitor in 200 patients.

Two hundred patients at a median age of 63 years, receiving conventional levodopa therapy for 8 years, who had had Parkinson's disease for 10 years, tried a regimen of selegiline (L-deprenyl), a type B monoamine oxidase inhibitor, at a daily dose of 10 mg, for varying periods from less than 6 months to more than 24 months (28% over 24 months). Selegiline does improve parkinsonism during the initial 6 months to 12 to 24 months of combined therapy in one third to almost half of patients with an end-of-dose type of response to long-term levodopa therapy. However, even this particular class of patients is unable to maintain such an improvement by 36 months, much less by 48 months, from the start of the selegiline trial. About one quarter of poor responders to levodopa and those with random deterioration show improvement in their parkinsonian status in the first 6 months of the selegiline trial, but their conditions quickly deteriorate by 1 year. The predominant pattern of response to previous levodopa therapy and the severity of the total disability score at the initiation of the selegiline trial were the two variables that were predictive of risk of failure with the drug. No evidence suggested that selegiline decreases the excess mortality rate of Parkinson's disease above that achieved with the use of levodopa alone. Selegiline as an adjunctive agent to conventional levodopa therapy was not unduly impressive with regard to preventing progression of Parkinson's disease.

Clinical Trials as Topic↗