Effortful and automatic memory: effects of dopamine.

With advancing age, there are changes in both cognitive functions and neurotransmitter metabolism. Dopamine plays a role in learning, memory, and related cognitive processes. We evaluated the effects of supplemental dopamine in precursor form (levodopa) on various aspects of memory in elderly normal volunteers in a controlled, double-blind study.

A new indirect method for measuring spinal conduction velocity in man.

A non-invasive, indirect method for measuring spinal cord mixed afferent-efferent conduction is described. The method is based upon eliciting late reflex responses labelled R1 and R2 from voluntarily contracting thenar and tibialis anterior muscles by preferentially stimulating median and common peroneal sensory nerve fibres. The mean onset latencies of R1 measured 27.

Diagnosis and management of Parkinson's disease.

Advances in the understanding of parkinsonism have done much to ensure correct diagnosis and more rational management. The authors offers an updated approach to the difficult-to-diagnose early stages, as well as management strategies for the duration of the disease.

Disposition of oral lisuride in Parkinson's disease.

The single and multiple oral dose plasma kinetics of lisuride were followed by a recently developed radioimmunoassay method in 11 patients with Parkinson's disease. A very wide range of plasma drug concentrations resulted from a single dose of 300 micrograms, as reflected in large interindividual differences in peak concentration (0.27 to 3.

Cerebral glucose metabolism in Parkinson's disease.

Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using 18F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus.

L-dopa decarboxylation in chronically treated patients.

We measured decarboxylation of oral L-dopa in patients chronically treated with L-dopa, and in untreated controls. Chronic L-dopa and carbidopa administration did not affect the extent of whole-body decarboxylation, and it is therefore unlikely that on-off fluctuations are related to chronic changes in the activity of L-aromatic amino acid decarboxylase. The observed duration of action and dose-response properties of carbidopa suggested that current empirically based dose schedules are optimal and supported the concept that decarboxylase inhibitors enhance the clinical effect of L-dopa largely by reducing the extent of first-pass metabolism rather than through an action on the decarboxylase enzyme in cerebral capillaries.

Dopamine agonists in Parkinson's disease.

Dopamine agonists have yielded two important advances to our understanding of the basal ganglia--they have facilitated the subdivision of different classes of dopamine receptors, and they have established the fact that important dopaminergic effects can be achieved by activation of dopamine receptors in a manner that is unrelated to anoxal impulse traffic in dopaminergic neurons--a phenomenon similar in its diffuse, slow, characteristics to an endocrine effect. The tangible clinical benefit of dopamine agonists has been evident in patients with prominent dyskinesia or wearing off reactions. It is possible that earlier use of agonists, in low doses combined with similarly low doses of levodopa, may improve the long term treatment of Parkinson's disease, but as yet there is no firm evidence.

Assessment of Parkinson's disease.

The quantitative assessment of clinical deficits in Parkinson's disease has become more difficult due to such factors as the introduction of therapy that induces involuntary movements, the recognition of marked fluctuations in response to treatment, and an increasing of memory disturbance in patients. An attempt to take these problems into account using a brief and simple scale of evaluation is presented.

Dopamine agonists and Parkinson's disease.

The therapeutic use of dopamine agonists for Parkinson's disease, clinical guidelines for their introduction into antiparkinson regimens, and their range of adverse effects are reviewed. The role played by the dopaminomimetic ergots in elucidating dopamine receptor function, and laboratory methods that identify dopamine agonists, are also examined.

Aetiology of Parkinson's disease.

It is suggested here that in most cases of Parkinson's disease the cause may be an environmental factor, possibly toxic, superimposed on a background of slow, sustained neuronal loss due to advancing age.

Episodic hyperhidrosis, hypothermia, and agenesis of corpus callosum.

Episodic hyperhidrosis and hypothermia are the primary symptoms of a rare central nervous system disorder of thermoregulation which is often associated with agenesis of the corpus callosum and can present in childhood or adult years. During attacks, patients may exhibit confused, withdrawn, and lethargic behavior and ataxia or other neurologic symptoms. A 21-year-old man with temperature chronically between 30 and 32 degrees C transiently responded to phenobarbital and to cyproheptadine therapy.

Comparison of pergolide and bromocriptine therapy in parkinsonism.

Twenty-four parkinsonian patients compared pergolide and bromocriptine therapy in a randomized double-blind, two-period crossover study. Both drugs were adjusted to an optimal balance between benefits and side effects. The mean daily dose and dose range for pergolide and bromocriptine were 3.

Olfactory impairment in Parkinson's disease.

In comparison with closely matched controls, patients with Parkinson's disease had reduced scores in tests of odor detection and qualitative discrimination. Olfactory impairment was not related to age, duration of symptoms, treatment, intellectual function, or genetic factors and seemed to be a nonmotor manifestation of the disease.

Parkinson's disease in 65 pairs of twins and in a set of quadruplets.

Among 43 monozygotic (MZ) and 19 dizygotic (DZ) pairs in which an index case had definite Parkinson's disease (PD), only one MZ pair was definitely concordant for PD. When pairs with questionable clinical features were included, 4 of 48 MZ and 1 of 19 DZ pairs were concordant. The frequency of PD in MZ cotwins of index cases with PD was similar to that expected in an unrelated control group matched for age and sex.

Current views on Parkinson's disease.

Since the introduction of levodopa therapy, there have been major advances in the understanding and treatment of Parkinson's disease. However, the problems and limitations associated with this form of treatment are now becoming increasingly apparent. This article reviews some of the current knowledge concerning the etiology and pathophysiology of Parkinson's disease and discusses some practical approaches to drug therapy.

Methods for evaluating treatment in Parkinson's disease.

Objective measurements of movement time, reaction time, and gait were compared with a clinical rating performed at the same times on several occasions in 10 patients with Parkinson's disease (PD). Positive correlations between objective measures and clinical evaluation were demonstrated. Movement time was the single most useful index of motor deficit, but no objective tests were more sensitive than clinical evaluations in the detection of motor disorder.

Lisuride treatment in Parkinson's disease: clinical and pharmacokinetic studies.

Our study of 28 patients has shown lisuride to share a comparable profile of antiparkinsonian effects and adverse reactions to that found with bromocriptine. The similarity in clinical response to lisuride and bromocriptine in the same group of patients contrasts with the pharmacological differences that have been established between them in animal studies. There were considerable individual differences in the patients' preference of bromocriptine or lisuride.

Atenolol vs. propranolol in essential tremor. A controlled, quantitative study.

The beta-1 selective, hydrophilic adrenoceptor blocking drug atenolol (100 mg daily) was compared to the non-selective, lipid-soluble beta-blocker propranolol (240 mg daily), and to placebo, in a double-blind cross-over study in 24 patients with essential tremor. Atenolol and propranolol caused a similar decrease in heart rate. Both beta-blockers also suppressed the tremor intensity; there was no significant difference between them, but both were significantly better than placebo.

Metabolism of (-) deprenyl to amphetamine and methamphetamine may be responsible for deprenyl's therapeutic benefit: a biochemical assessment.

The urinary excretion of some important phenylethylamines, catecholamines, their metabolites, amphetamine, and methamphetamine were measured in parkinsonian patients on Sinemet (L-dopa plus carbidopa, a peripheral dopadecarboxylase inhibitor) and depressed patients after chronic (-) deprenyl treatment. Deprenyl was efficiently metabolized to amphetamine and methamphetamine. It increased the excretion of phenylethylamine and of m- and p-tyramine, and reduced the output of norepinephrine metabolites, but failed to alter the excretion of dopamine-deaminated metabolites.