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Biomedical subjects

S Fahn

Publications and source records attributed to S Fahn.

At least 307 records · Page 17Linked to original sources
PubMed1984

Chronic levodopa or pergolide administration induces down-regulation of dopamine receptors in denervated striatum.

Refractory response to dopamine (DA) agonists is a common problem in the treatment of Parkinson's disease. In rats with unilateral lesions of the substantia nigra, denervation induced significant increases in striatal 3(H)-spiperone binding sites ipsilateral to the lesion. Chronic treatment with levodopa or with pergolide mesylate significantly decreased the number of 3(H)-spiperone striatal binding sites. Agonist-induced decreases were approximately equivalent in intact and denervated striata and did not appear to be affected by lesions. These results suggest that the poor response to DA agonist in certain parkinsonian patients with chronic drug exposure may be mediated by drug-induced DA receptor down-regulation.

Animals↗
PubMed1984

The varied clinical expressions of dystonia.

This article describes the myriad clinical appearances of dystonic movements. The phenomenology of the movements varies according to the region of the body affected, but even within the same region there is a wide variation. Arguments were presented that dystonic movements consists of both slow, sustained contractions, and rapid, repetitive, twisting movements, especially in the earlier stages of the disease called "dystonia musculorum deformans," also known as primary torsion dystonia.

Adolescent↗
PubMed1984

Practical management of dystonia.

The diagnosis of dystonic movements is based on the phenomenologic characteristics of the movements themselves. Therefore to evaluate and manage the patient, it is important to be cognizant of the varied clinical appearances; to classify the type of dystonia according to age at onset and distribution of the movements; to determine its etiology; to treat with specific therapy if available; and to reduce the symptoms, if therapy is not available. These steps are the focus of this article.

Age Factors↗
PubMed1984

Catechol-O-methyltransferase and Parkinson's disease.

OMD inhibits L-DOPA utilization in rat corpus striatum. This effect is probably mediated through competition with L-DOPA for brain uptake mechanism. Such competition may explain the inhibition exerted by OMD on L-DOPA-induced rotation in rats with unilateral destruction of the nigrostriatal pathway. U-0521, a potent COMT inhibitor, was shown, after i.p. injection, to effectively block the accumulation of OMD in the plasma and to enhance L-DOPA metabolism in rat brain. This drug, however, was not active when given orally to rats and to a single patient with Parkinson's disease. It is suggested that the combined use of L-DOPA plus an orally active COMT inhibitor may be useful in future treatment of Parkinson's disease.

Animals↗
PubMed1983

Chlorpromazine methiodide acts at the vestibular nuclear complex to induce barrel rotation in the rat.

Barrel rotation is a unique motor response observed in rats in which, following an intracerebral injection, the animal develops a twist about the long axis and rolls laterally repeatedly. The response was first described following injection of somatostatin. We have previously shown that 'experimental dystonia' in rats induced by intraventricular chlorpromazine methiodide (CPZMI) is identical to barrel rotation, and that it is due to an antimuscarinic effect. The purpose of the present study was to investigate the neuroanatomical basis of CPZMI-induced rotation. We injected CPZMI in 3 microliters into right lateral and IVth ventricle and found that IVth ventricle injections were significantly more likely to induce rotation. Nuclear groups adjacent to the IVth ventricle, which are rich in muscarinic cholinergic receptors, include locus coeruleus and vestibular nuclear complex (VNC). We found that only VNC injections induced rotation. Only certain control compounds injected into VNC elicited the response. We conclude that barrel rotation has a specific neuroanatomical basis, involving central vestibular mechanisms, and that it has a specific pharmacologic basis.

Animals↗
PubMed1983

Lithium attenuates dopamine depleting effects of reserpine and tetrabenazine but not that of alpha methyl-p-tyrosine.

Concurrent administration of lithium (Li) significantly attenuates the dopamine (DA) depleting effects of reserpine and tetrabenazine, but does not change alpha-methyl-p-tyrosine (AMPT) induced DA depletion in rat brain. This effect of Li is probably mediated, in part, by inhibiting the magnesium-dependent binding of both reserpine and tetrabenazine to their specific receptor sites. Such interaction between these drugs may attenuate the beneficial effects of tetrabenazine and reserpine on patients with tardive dyskinesia or tardive dystonia who are treated concurrently with lithium for their psychiatric disorder.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Lithium interferes with reserpine-induced dopamine depletion.

Long-term lithium treatment attenuated the hypokinetic effect of reserpine in a patient with tardive dyskinesia. In rats, prophylactic lithium administration inhibits reserpine-induced dopamine depletion in the brain. These data indicate that lithium may limit the therapeutic efficacy of reserpine in tardive dyskinesia.

Adult↗
PubMed1983

Electroencephalographic studies of chlorpromazine methiodide and somatostatin-induced barrel rotation in rats.

It has been reported that intraventricular injection of chlorpromazine methiodide (CPZMI), a quaternary ammonium derivative of chlorpromazine, in rats induces abnormal, twisting postures which may serve as an experimental model of the human movement disorder dystonia. We have shown elsewhere that the behavior induced by intraventricular CPMZI is identical to what has been called "barrel rotation," first observed to follow intraventricular injection of somatostatin (SRIF), which consists of twisting about the long axis, with repetitive lateral rolling. The suitability of barrel rotation, induced by CPZMI or SRIF, as an experimental model for dystonia depends on its physiologic basis. Human dystonia is clinically not a convulsive phenomenon. SRIF-induced barrel rotation has been reported to be associated with epileptiform activity recorded by the electroencephalogram (EEG). The purpose of this study was to investigate EEG activity during CPZMI- and SRIF-induced rotation. We found that CPZMI barrel rotation was not associated with epileptiform activity in cortex, amygdala, or hippocampus, and contrary to prior reports, neither was SRIF rotation. Both CPZMI and SRIF injected in high doses could induce epileptiform activity, but this was associated with clonic motor phenomena and not barrel rotation. We conclude that electroencephalographic criteria do not exclude either CPZMI- or SRIF-induced rotation as models for movement disorders, but their validity as such requires further study.

Animals↗
PubMed1983

Studies of somatostatin-induced barrel rotation in rats.

Somatostatin (SRIF) has been reported to induce abnormalities of motor behavior in rats when injected intraventricularly. Following an injection, non-lesioned rats develop unilateral extension of the limbs, a twist about the long axis, and repeated lateral rolling, called "barrel rotation". It has not been clear whether this behavior is due to a pharmacologic action of SRIF, such as an effect of SRIF on systems of motor control. Prior reports observed the response only at high doses of SRIF, and found no dose-response relationship for it. We have investigated whether this response is due to a pharmacologic effect of SRIF. We have also studied where SRIF acts, when injected intraventricularly, to induce this response. We have found that SRIF-induced rotation increases linearly with doses up to 10 micrograms and thereafter declines. Biologically inactive analogues of SRIF did not induce barrel rotation. Dose-response studies of intraventricular and intracerebral microinjections indicated that SRIF acts at the vestibular nuclear complex (VNC) to induce rotation. At VNC, 0.25 micrograms SRIF produced postural abnormalities. We conclude that barrel rotation is due to a pharmacologic action of SRIF, and that SRIF does act upon a system of motor control, the VNC, to induce this response.

Animals↗
PubMed1983

Treatment of tardive dyskinesia: use of dopamine-depleting agents.

Four different clinical syndromes encompassing the TD spectrum are described: (a) classical TD, which is choreatic in speed of movement and stereotypic in pattern; (b) tardive akathisia; (c) withdrawal emergent syndrome, which presents as true chorea; and (d) tardive dystonia, which presents with dystonic movements and postures. All are made worse or are unmasked by withdrawal of the antipsychotic drugs, and all tend to be reduced in severity by increasing the dosage of the antipsychotic drugs (dopamine-receptor blockers) or utilizing presynaptically acting dopamine-depleting drugs. Treatment depends on discontinuing the causative agent, i.e., the antipsychotic drugs. The withdrawal emergent syndrome is self-limiting. Classical TD and tardive akathisia are persistent. The dopamine-depleting agents can be utilized if the symptoms are severe. Reserpine alone or with AMT is effective in most cases. Tetrabenazine can be substituted for reserpine. With time, the disorder can eventually disappear in many patients as long as the antipsychotic drugs have been eliminated. Carbidopa/levodopa (Sinemet) can be added to counteract parkinsonian symptoms that occur as an adverse effect of these medications. The addition of Sinemet may be useful in hastening a remission of TD. Tardive dystonia is less successfully treated. Some patients will respond to the approach used to treat classical TD, others may respond to anticholinergic agents, and some remain resistant to these methods. They may require reinstitution of the antipsychotic drugs.

Adult↗
PubMed1983

High dosage anticholinergic therapy in dystonia.

Twenty-three children and 52 adults with torsion dystonia of various etiologies and distribution patterns of the involuntary movements were treated in an open-label study with anticholinergic medication. The dosage was increased gradually until there was either benefit or intolerable adverse effects. Trihexyphenidyl was used initially, but later ethopropazine was given to adult subjects. Significant benefit occurred in 61% of children and in 38% of adults. The average daily dosages were 41 mg trihexyphenidyl for children, 24 mg trihexyphenidyl for adults, and 350 mg ethopropazine for adults. Adverse effects were the major limiting factor to high dosage in adults, but not in children.

Adolescent↗
PubMed1983

Normal erythrocyte uptake of L-DOPA in Parkinson's, Huntington's, and related diseases.

We measured the kinetic constants for the unidirectional influx of L-DOPA into red blood cells of patients with Parkinson's disease (seven patients), Huntington's disease (seven patients), and other extrapyramidal diseases (11 patients), and in five controls. Influx consisted of two components with low affinity and high exchange capacity. In individual subjects, the L-DOPA concentration giving half-maximal influx (Km) varied between 0.04 and 2.19 mM, and the maximum velocity (Vmax) of the saturable transport component was between 20 and 578 mumol/l cell water/h, which is compatible with the neutral amino acids of low affinity for the transport system. The range of Kd (the first-order rate constant for the unsaturable component) was between 0.11 and 0.36 hour-1. There was no gross deficit of the L-DOPA uptake process in patients with Parkinson's disease, Huntington's disease, dystonia, or other extrapyramidal diseases.

Biological Transport↗
PubMed1983

High-dosage anticholinergic therapy in dystonia.

Twenty-three children and 52 adults with torsion dystonia of various etiologies and distribution patterns of the involuntary movements were treated in an open-label study with anticholinergic medication. The dosage was build up gradually until there was either benefit or tolerable adverse effect. Trihexyphenidyl was used initially, but beginning in 1979, ethopropazine was utilized in the adult subjects. Significant benefit occurred in 61% of children and in 38% of adults.

Adult↗
PubMed1983

Normal pressure hydrocephalus and Parkinson's disease.

Three patients with normal pressure hydrocephalus and Parkinson's disease are reported. The recognition of this association is important because these two entities require specific therapeutic approaches. The presence of Parkinson's disease does not preclude an excellent response of the hydrocephalus to a shunting procedure. Although several reports of cases with the characteristic clinical manifestations of normal pressure hydrocephalus--progressive dementia, gait difficulty and urinary incontinence--have been published earlier, it was Adams and Hakim who emphasized the clinical triad and the effect of shunting the cerebrospinal fluid as a means of treatment. Messert and Baker stressed that the gait disturbance had a close resemblance to the freezing gait of parkinsonism. We are reporting three patients who had both conditions. Recognition of the existence of both disorders in the same patients is important since appropriate treatment of each of them led to marked improvement of their symptoms.

Aged↗