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Biomedical subjects

J H Pincus

Publications and source records attributed to J H Pincus.

At least 37 records · Page 2Linked to original sources
PubMed1988

Protein redistribution diet restores motor function in patients with dopa-resistant "off" periods.

Sixteen parkinsonians with acquired drug-resistant "off" periods without dyskinesia were placed on a diet in which virtually all protein was concentrated in the evening meal. Restoration of sensitivity to levodopa resulted in 88%. Ten patients (62%) have continued to comply with the diet for 7 months (mean). Two patients were studied in detail. Immobility correlated with elevated plasma levels of large neutral amino acids (LNAA), normality with low LNAA.

Amino Acids↗
PubMed1987

Influence of dietary protein on motor fluctuations in Parkinson's disease.

On a nearly zero protein diet, 11 patients with Parkinson's disease with the "on-off" effect demonstrated great sensitivity to levodopa (L-dopa)-carbidopa and reduced fluctuations. Eight patients required a 41% reduction in total L-dopa dosage and discontinuation of all adjuvant therapy to reduce the preponderance of chorea. On a high-protein diet, all patients were immobilized by bradykinesia for most of the day. A low-protein dietary regimen during the daytime offers an important technique for the control of fluctuations in patients with Parkinson's disease who are receiving L-dopa-carbidopa.

Aged↗
PubMed1987

Plasma levels of amino acids correlate with motor fluctuations in parkinsonism.

Seven patients with Parkinson's disease who experienced severe motor fluctuations in response to levodopa were studied in detail with relation to the effect of dietary protein on their motor function. The levodopa dose for each patient was not changed during the period of study, and no other antiparkinsonian drugs were used. Regular and high-protein diets resulted in a marked elevation in the plasma concentrations of large neutral amino acids (LNAAs) that are known to compete with levodopa for transport across the blood-brain barrier. Despite elevated plasma levodopa levels, all patients with elevated LNAA levels experienced parkinsonian symptoms. When the amino acid level dropped while plasma levodopa levels were elevated, patients experienced relief of these symptoms. On a low-protein diet, LNAA levels remained low and all patients were consistently dyskinetic throughout the day, even though the mean plasma levodopa levels were somewhat lower than when the patients consumed a high-protein diet. A redistribution diet that is virtually protein free until supper and then unrestricted until bedtime is tolerated by patients because this simple manipulation permits near-normal daytime motor function.

Amino Acids↗
PubMed1986

Phenytoin reduces early acetylcholine release after depolarization.

Phenytoin 10 microM inhibits the K-evoked release of acetylcholine (ACh) from synaptosomes, a process which is biphasic. Phenytoin acts only on the early phase of release. Replacement of external Na with Li does not modify phenytoin's effect. Phenytoin augments the spontaneous release of ACh from resting synaptosomes but this effect is eliminated in Li media. It is likely that phenytoin reduces K-evoked Ca uptake and the Na/Ca exchange by separate mechanisms.

Acetylcholine↗
PubMed1986

Phenytoin: mechanisms of its anticonvulsant action.

Phenytoin is a major anticonvulsant drug that is very effective in controlling a wide variety of seizure disorders while impairing neurological function little, if at all. Early work suggested the hypothesis that the drug's effects were due to a selective block of high-frequency neuronal activity. This theory is reevaluated in the light of accumulated observations on the effects of phenytoin in many neuronal and synaptic preparations. Most of these observations can be explained by a use- and frequency-dependent suppression of the sodium action potential by phenytoin, with a consequent filtering out of sustained high-frequency neuronal discharges and synaptic activity. The molecular mechanism for this is a voltage-dependent blockade of membrane sodium channels responsible for the action potential. Through this action, phenytoin obstructs the positive feedback that underlies the development of maximal seizure activity, while normal brain activity, proceeding at lower neuronal firing rates, is spared its depressant action. Other mechanisms of action that may contribute to the drug's efficacy and selectivity are also discussed.

Action Potentials↗
PubMed1986

Phenytoin, tetrodotoxin, and acetylcholine release.

To determine if phenytoin reduces depolarization-linked acetylcholine release from synaptosomes solely by interacting with Na+, the effect of phenytoin (100 to 200 microM) and/or tetrodotoxin (1 microM) on ACh release was assayed in synaptosomes depolarized with either KCl 56 mM or veratridine 10 microM. Phenytoin reduced release in both depolarizing solutions. In KCl the effect of phenytoin was greater at 200 microM than 100 microM but with veratridine, phenytoin 200 microM was not more effective than 100 microM. Tetrodotoxin failed to affect release induced by KCl but the effect of tetrodotoxin and phenytoin on veratridine-stimulated release was much greater than that with phenytoin alone 100 microM. In conclusion, the inhibition of acetylcholine release by phenytoin must be independent of any effect of the drug on Na conductance.

Acetylcholine↗
PubMed1986

Psychiatric, neurological, and psychoeducational characteristics of 15 death row inmates in the United States.

The authors present the results of clinical evaluations of 15 death row inmates, chosen for examination because of the imminence of their executions and not for evidence of neuropsychopathology. All had histories of severe head injury, five had major neurological impairment, and seven others had other, less serious neurological problems (e.g., blackouts, soft signs). Psychoeducational testing provided further evidence of CNS dysfunction. Six subjects had schizophreniform psychoses antedating incarceration and two others were manic-depressive. The authors conclude that many condemned individuals probably suffer unrecognized severe psychiatric, neurological, and cognitive disorders relevant to considerations of mitigation.

Adult↗
PubMed1985

Effect of phenytoin on [3H]norepinephrine release from synaptosomes.

Phenytoin reduces depolarization-linked [3H]norepinephrine release from rat brain synaptosomes. When choline chloride was substituted for NaCl the phenytoin effect was attenuated but still significant. This is consistent with the theory that phenytoin reduces both Na and Ca influx during depolarization.

Animals↗
PubMed1984

Acetylcholine release from synaptosomes and phenytoin action.

The release of labeled acetylcholine from synaptosomes loaded with methyl-[3H]choline has been measured in Krebs-Ringer-Bicarbonate (KRB) media containing either 5.6 or 56 mM KCl. Experiments have been performed in media containing either 1.0 mM Ca or 0 Ca with 1 mM EGTA. Phenytoin, 2 X 10(-4) M, reduced the depolarization-dependent release of acetylcholine in media containing 1.0 mM Ca and 56 mM KCl. It also significantly increased the release of acetylcholine from undepolarized samples in 5.6 mM KCl irrespective of the Ca concentration. The drug did not affect release from synaptosomes depolarized in Ca-free media. These results confirm the hypothesis that phenytoin has a dual effect on transmitter release.

Acetylcholine↗
PubMed1982

The medical assessment of seriously delinquent boys: a comparison of pediatric, psychiatric, neurologic, and hospital record data.

This study documents a high prevalence of medical disorders, especially head and face injury, seizures, and other neurological problems in violent incarcerated adolescent delinquents. It documents the failure of three different medical specialities--pediatrics, psychiatry, and neurology--to consistently elicit significant potentially treatable disorders during routine evaluations. It explores possible causes for overlooking significant medical factors in these youngsters and proposes ways to improve the health evaluations of delinquent adolescents.

Adolescent↗
PubMed1982

Psychomotor epilepsy and violence in a group of incarcerated adolescent boys.

The authors report the finding of psychomotor epilepsy in 18 of 97 incarcerated delinquent boys. Number of psychomotor symptoms was correlated with degree of violence in the members of this group. In addition, psychomotor symptoms were correlated more strongly with certain psychotic symptoms than with soft neurological signs or intellectual deficits. The relationship of violence to ictal and interictal states is explored.

Adolescent↗
PubMed1981

Calcium uptake mechanisms affected by some convulsant and anticonvulsant drugs.

An anticonvulsant (phenytoin) and a convulsant barbiturate (5-(2-cyclohexylidene ethyl)-5-ethyl-barbituric acid) (CHEB) reduced depolarization-coupled 45Ca uptake by synaptosomes from rat brain. CHEB reduced uptake to the level of undepolarized control samples. Phenobarbital failed to affect synaptosomal 45Ca uptake. Phenobarbital inhibited mitochondrial 45Ca uptake by 38%. CHEB was even more effective, lowering mitochondrial 45Ca uptake nearly to the levels induced by the mitochondrial inhibitors KCN, ruthenium red and dinitrophenol. Phenytoin, phenobarbital and CHEB did not affect ATP-dependent 45Ca uptake by the endoplasmic reticulum in lysed synaptosomes. In view of the effect of CHEB, a known convulsant, in limiting Ca uptake by depolarized synaptosomes, an effect which was greater than either that of phenytoin or phenobarbital, an identification of such a mechanism with anticonvulsant or sedative properties may be oversimplified.

Adenosine Triphosphate↗