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Biomedical subjects

I Shoulson

Publications and source records attributed to I Shoulson.

102 records · Page 6Linked to original sources
PubMed1975

Fenfluramine in man: hypophagia associated with diminished serotonin turnover.

A double-blind trial of orally administered fenfluramine was conducted in 7 non-obese adults with various neurological disorders. Caloric intake and body weight fell significantly after 8 days of treatment although there was no definite change in appetite ratings. Average central turnover of serotonin, as estimated by the cerebrospinal fluid (CSF) accumulation of 5-hydroxyindoleacetic acid (5-HIAA) during probenecid loading, decreased by 66%. No significant change in homovanillic acid, the major dopamine product, was apparent. The results support the contention that the effect of fenfluramine on human dietary intake may be mediated by alterations in serotonergic rather than dopaminergic mechanisms.

Adult↗
PubMed1975

On-off response. Clinical and biochemical correlations during oral and intravenous levodopa administration in parkinsonian patients.

Seven parkinsonian patients who had severe on-off effects during chronic treatment with levodopa were studied. Marked swings in plasma dopa levels as well as in motor function followed each oral dose of levodopa. A constant intravenous infusion of levodopa resulted in stable plasma dopa concentrations and virtual disappearance of motor fluctuations. Notwithstanding steady plasma dopa levels, an abrupt decline in the antiparkinsonian response to levodopa attended postural tilting or cold pressore stimulation. Although these maneuvers were accompanied by a significant rise in plasma norepinephrine, the intravenous infusion of this catecholamine failed to influence the effect of levodopa on parkinsonian signs. The results suggest that central noradrenergic mechanisms as well as alterations in circulating dopa may contribute to the on-off response to levodopa.

Administration, Oral↗
PubMed1975

Caffeine and the antiparkinsonian response to levodopa or piribedil.

The ability of orally administered caffeine to modify the antiparkinsonian efficacy of levodopa of piribedil, a putative dopamine receptor against, was studied in six patients. At doses that induced unequivocal central nervous system stimulation, caffeine produced no change in the therapeutic response to either antiparkinsonian agent. On the other hand, patients with levodopa dyskinesias reported an increase in the duration of their involuntary movements with caffeine coadministration. Since caffeine is known to stimulate both dopaminergic mechanisms and motor activity in the experimental animal, the results of this study cast doubt on the value of these factors as predictors of therapeutic efficacy in parkinsonian patients.

Adult↗
PubMedDate not supplied

Homozygotes for Huntington's disease.

Careful comparison of symptomatic individuals with normal controls has revealed the primary biochemical abnormality in many human genetic diseases, particularly recessive disorders. This strategy has proved less successful for most human disorders which are not recessive, and where a single copy of the aberrant gene has clinically significant effects even though the normal gene product is present. An alternative approach that eliminates the impediment of a normal protein in affected individuals is to study homozygotes for the mutant allele. For virtually all dominant human disorders in which homozygotes have been described, symptoms have been significantly more severe in the homozygote than in the heterozygote. Thus, these disorders do not conform to the classical definition of dominance which states that homozygotes and heterozygotes for a defect are phenotypically indistinguishable. Instead, they display incomplete dominance, indicating that the normal allele may play a role in ameliorating the disease process. The D4S10 locus, defined by the probe G8 and linked to the gene for Huntington's disease (HD), has permitted us to identify individuals with a high probability of being homozygous for this autosomal dominant neurodegenerative disorder. These homozygotes do not differ in clinical expression or course from typical HD heterozygotes. HD appears to be the first human disease of genetically documented homozygosity that displays complete phenotypic dominance.

Genes, Dominant↗