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Biomedical subjects

A Lieberman

Publications and source records attributed to A Lieberman.

At least 19 recordsLinked to original sources
PubMed1992

An integrated approach to patient management in Parkinson's disease.

New concepts about the pathogenesis and pathophysiology of Parkinson's disease have emerged. For these concepts to be useful, they must be understood, and for them to be applied, the psychology of the patient and the patient's family must be understood. The initial consultation is crucial in establishing a successful relationship between a patient, family, and physician. This consultation is analyzed and ways of avoiding errors and misconceptions delineated. Emphasis is placed on imaginitive questioning using the format of the ADL portion of the UPDRS in establishing the diagnosis and following treatment. The rational for starting treatment with selegiline at this time is discussed in the context of the role that increased MAO-B activity plays in the progression of Parkinson's disease. After making the diagnosis and starting treatment with selegiline, deciding when to start levodopa is the next crucial decision. Often as important as deciding when to start levodopa is overcoming the resistance of the patient to accept this treatment. The next crucial decision occurs after the patient develops response fluctuations on levodopa. A format for assessing the fluctuations is presented, and the merits of different treatments, including selegiline, dopamine agonists (bromocriptine and pergolide), and sustained-release or controlled-release levodopa preparations (Sinemet CR), discussed. The management of patients with depression, sleep problems, and advanced disease including postural instability and mental changes are reviewed.

Activities of Daily Living↗
PubMed1992

Dopamine agonists used as monotherapy in de novo PD patients: comparisons with selegiline.

Studies indicate that selegiline, a monoamine oxidase type B inhibitor, slows progression of Parkinson's disease (PD) and delays the need for levodopa. While dopamine agonists also delay the need for levodopa because of their symptomatic, antiparkinsonian effect, only recently has it been proposed that agonists may also have a protective effect. When dopamine agonists are used as monotherapy in newly diagnosed PD patients, fewer patients improve than on levodopa, but fewer patients develop response fluctuations. This might indicate that dopamine agonists have a protective, as well as a symptomatic, effect, as the lack of response fluctuations may indicate that dopamine agonists protect nigral neurons. Response fluctuations may result from destruction of nigral neurons.

Bromocriptine↗
PubMed1992

The role of the regulatory enzymes of catecholamine synthesis in Parkinson's disease.

The major neuropathology of Parkinson's disease (PD) is the degeneration of nigrostriatal dopamine (DA), resulting in a deficiency of DA, and of the enzyme tyrosine hydroxylase (TH), which catalyzes the synthesis of L-dopa. The symptomatic treatment of PD consists of replenishing DA by administering L-dopa, which is enzymatically converted to DA in the striatum. The increase of TH activity by modification of the enzyme leads to an increased synthesis of striatal L-dopa, and thereby replenishes the missing DA more efficiently. The activity of TH is increased by protein kinase-dependent phosphorylation of the enzyme or by inhibition of dephosphorylation with specific phosphatase inhibitors. Thus, modification of TH results in an activated form of the enzyme, which might provide a basis for developing new strategies in the treatment of PD. The extraneuronal enzyme, catechol-O-methyl transferase (COMT), inactivates catecholamines by O-methylation, and its inhibition leads to increased levels of striatal DA. The availability of selective and nontoxic COMT inhibitors makes it possible to assess their therapeutic role in treatment of PD. The intraneuronal enzymes, monoamine oxidase (MAO)-A and MAO-B, inactivate catecholamines and other biogenic amines, such as serotonin, by deamination. Inhibition of these enzyme activities leads to increased levels of striatal DA. The irreversible MAO-B inhibitor selegiline was shown to exert antiparkinsonian activity, especially in the early stages of parkinsonism. Selegiline also prevents the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in MPTP-treated mice and monkeys. Its role in the prevention of the disease is under investigation in several clinical centers.

Catechol O-Methyltransferase↗
PubMed1992

Long-term experience with selegiline and levodopa in Parkinson's disease.

Between 1982 and 1989, 197 patients with Parkinson's disease were treated with selegiline and levodopa for at least 0.3 years. Two groups of patients were included: a group of 65 patients (stage 2 or 3 on the Hoehn and Yahr Scale) who recently had been started on levodopa and were not experiencing response fluctuations, and a group of 132 patients on levodopa who were experiencing fluctuations. More nonfluctuating than fluctuating patients improved, although the differences were not significant; a higher percentage of fluctuating patients worsened, compared with nonfluctuating patients, and these differences were significant. The percentage of patients who were stable was similar between the two groups, and adverse effects were minor and reversible. Our study suggests that among patients on levodopa, fewer patients worsen when selegiline is added earlier than when it is added later.

Aged↗
PubMed1991

Experience with selegiline and levodopa in advanced Parkinson's disease.

We compared the results of treatment with selegiline (deprenyl, Eldepryl) in 17 patients with advanced Stage 4 Parkinson Disease (PD) who were on levodopa (as Sinemet) with 65 Stage 2 or 3 patients with early PD who were also on levodopa. The first group consisted of 17 patients with advanced Stage 4 PD without response fluctuations ("wearing off" or "on off" phenomena). Their mean age was 72.1 +/- 7.5 years, their mean duration of PD was 7.4 +/- 3.2 years. The second group consisted of 65 patients with Stage 2 or 3 PD who had recently been started on levodopa. Their mean age was 63 +/- 12.1 years, their mean duration of PD was 7.4 +/- 3.2 years. The mean dose of selegiline was 10.0 +/- 1.8 mg per day (range 5-20 mg). The mean duration of treatment was 1.5 +/- 0.8 years. During the four years of observation 55.3 +/- 8.0% of the Stage 2 or 3 patients improved while only 14.3 +/- 13.5% of the Stage 4 patients improved. This difference was significant (p less than 0.05). During this time 22.0 +/- 6.7% of the Stage 2 or 3 patients worsened and 60.7 +/- of the Stage 4 patients worsened. This degree of worsening was significant (p less than 0.05). Adverse effects were minor and reversible. Our observations suggest that selegiline is more effective (higher percent of patients improving, lower percent of patients worsening) when it is added earlier with patients on levodopa than when it is added later.

Aged↗
PubMed1979

Dementia in Parkinson Disease.

In 520 patients with parkinsonism seen over eight years, 168 (32%) had moderate to marked dementia. Although the demented patients were older than the nondemented patients (70.4 versus 65.5 years), the incidence of dementia in Parkinson's disease (PD) was tenfold higher than among controls (similarly aged spouses of PD patients), and dementia is held to be related more to the disease than to age. Demented patients, in addition to being older, developed PD later, were more severely involved in a shorter time, and responded less well to levodopa. It is suggested that PD with dementia may represent a different disorder from PD without dementia.

Aged↗
PubMed1979

Training sensory awareness and spatial organization in people with right brain damage.

Building on a methodology to improve scanning and academic skill performance behavior in persons with acquired right brain damage due to stroke, this study presents 2 additional treatment methods: training in sensory awareness and spatial organization. The 53 patients studied were divided into two groups, experimental (N = 30) and control (N = 23). The experimental group received a treatment program incorporating the 2 new methods as well as a condensed version of the original program. The controls received standard rehabilitation. Both groups were retested after 1 month. Analyses revealed that the performance of those in the experimental group exceeded that of the controls, that those patients in the experimental group with severe impairments improved more than those with mild impairments, and that combined multiple-treatment produces greater generalization than the original single treatment program.

Activities of Daily Living↗
PubMed1978

Bromocriptine, lergotrile: the antiparkinsonian efficacy and the interaction with monoaminergic receptors.

The antiparkinsonian activity of bromocriptine and of lergotrile was investigated in monkeys with surgically induced tremor and in parkinsonian patients. Both drugs effectively relieve tremor in experimental monkeys and induce less pronounced abnormal involuntary movements than L-dopa or piribedil. Both drugs were shown to be of therapeutic value in a group of patients with advanced Parkinson's disease who were no longer responsive to levodopa combined with carbidopa. Adverse effects were similar to those observed with levodopa and carbidopa, except that in individual patients abnormal involuntary movements and diurnal oscillations in performance ("on-off" effect) were decreased, while mental changes were increased. The interactions of bromocriptine and of lergotrile with dopamine and alpha-adrenergic receptors were investigated. Both drugs have mixed agonist-antagonist activities with respect to the dopamine receptors; lergotrile has a higher affinity for the agonist site while bromocriptine has a higher affinity for the antagonist site of the receptors. Both drugs effectively displace the binding of the alpha-adrenergic antagonist WB-4101 to cerebral cortex membranes. The mechanisms underlying the antiparkinsonian efficacies of these two drugs were discussed.

Animals↗
PubMed1978

Binding interactions of ergot alkaloids with monoaminergic receptors in the brain.

The interactions of ergot alkaloids and of other drugs with dopamine (DA) and alpha-adrenergic receptors were investigated. The tested ergot alkaloids inhibit synaptosomal tyrosine hydroxylase activity and reverse the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity. Thus, ergot alkaloids interact as both agonists and antagonists with the presynaptic DA receptors. Ergot alkaloids also compete effectively for the binding of 3H-DA and 3H-haloperidol to bovine striatal membranes. These results show that these drugs are mixed agonist-antagonists with respect to the postsynaptic DA receptors. To determine the effects of ergot alkaloids and of neuroleptics on the alpha-adrenergic receptors in the CNS, we have measured their effects on the binding of 3H-dihydroergocryptine and 3H-WB-4101 to cerebral cortical membranes. The displacing potencies of the tested ergot alkaloids and of the neuroleptics indicated that they have a high affinity for the alpha-adrenoreceptors in the CNS. The mechanisms underlying the therapeutic efficacy of mixed agonist-antigonists of DA and alpha-adrenergic receptors in Parkinson's disease and in geriatric disorders were considered.

Animals↗
PubMed1978

An extraordinary form of confabulation.

We describe five patients with spontaneous, persistent confabulation. While the basis of confabulation in general is not known, the evidence in this specific group of patients with spectacular, impulsive, and spontaneous confabulation suggests a marked deficit in frontal function, superimposed upon a basic defect in memory, as a possible mechanism.

Adult↗