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Biomedical subjects

J P Frankel

Publications and source records attributed to J P Frankel.

At least 19 recordsLinked to original sources

Motor response to levodopa in patients with parkinsonian motor fluctuations: a follow-up study over three years.

To clarify the way in which the clinical response to levodopa changes with the progression of Parkinson's disease, a longitudinal study was performed to quantify motor response characteristics to single doses of levodopa by mouth over three years in 23 patients with fluctuating motor function. A significant increase in motor disability in "on" (time of peak motor improvement) and "off" (before levodopa dose) phases occurred and "on" phase dyskinesia increased by 24%, though the amplitude of motor response was conserved. There was no evidence of progressive loss of response of certain motor deficits affecting axial muscles and gait. The mean duration of motor response decreased by 17%. Both shortening of response duration and increase in "off" phase disability contribute to the development of motor fluctuations. A short response time to the levodopa test dose was not an invariable finding in patients with severe fluctuations, whereas all had large response amplitudes and high "off" phase disability scores. Patients who have developed motor fluctuations may continue to respond to dopaminergic treatment until late in the disease course, despite the unstable nature of their responses.

Adult

Comparison of motor response to apomorphine and levodopa in Parkinson's disease.

The magnitude and pattern of motor responses to single doses of subcutaneous apomorphine and oral levodopa were compared in 14 patients with Parkinson's disease. Although apomorphine produced much shorter motor responses than levodopa, the quality of response to the two drugs was virtually indistinguishable. These clinical observations support the notion that integrity of striatal post-synaptic dopamine receptors is a key determinant of responsiveness to dopaminergic treatment in Parkinson's disease.

Administration, Oral

Diurnal differences in response to oral levodopa.

Diurnal differences in duration and quality of motor response to levodopa are frequently described by patients. The quality and duration of motor responses were objectively assessed to morning and afternoon oral levodopa doses in five patients with Parkinsonian motor fluctuations who complained of diurnal variation in response to their normal levodopa medication. Results suggest that under controlled conditions which eliminated the effects of diet and overlapping levodopa effects the response to levodopa remained unchanged throughout the day, and that the duration of response could be predicted by plasma levodopa levels.

Administration, Oral

Subcutaneous apomorphine in the treatment of Parkinson's disease.

Apomorphine a dopamine receptor agonist was given subcutaneously to 57 levodopa treated parkinsonian patients with refractory off-period disabilities for a median period of 16 months. In 30 given intermittent suprathreshold injections the mean number of hours spent in a disabling off state fell from 6.9 to 2.9. Similar benefit was observed in 21 patients receiving continuous infusions with additional boluses on demand by mini-pump (mean reduction of hours off from 9.9 to 4.5). Twelve patients have been treated for over two years without tachyphylaxis or loss of response. The incidence of neuropsychiatric side-effects has been low (7%). Six patients failed to show a sustained worthwhile response; severe disabilities during "on" periods being the major problem. Subcutaneous apomorphine is proposed as an effective treatment for patients with incapacitating "off" period disabilities refractory to oral medication and should be considered before experimental implantation procedures.

Adult

Anal sphincter dysfunction in Parkinson's disease.

Striated anal sphincter function was studied electrophysiologically and radiologically in six patients with Parkinson's disease and chronic constipation. In five cases, there was paradoxic anal sphincter muscle contraction during simulated defecation straining resembling anismus-type pelvic outlet obstruction. Radiologic studies showed functional improvement of the defecatory mechanism following the administration of the dopamine receptor agonist apomorphine in four patients. Dysfunction of the striated anal sphincter musculature may be a significant cause of constipation in some parkinsonian patients, occurring as part of the generalized extrapyramidal motor disorder.

Anal Canal

Off-period belching due to a reversible disturbance of oesophageal motility in Parkinson's disease and its treatment with apomorphine.

Two L-dopa-treated patients with Parkinson's disease who developed distressing belching during "off" periods are reported. In each case, contrast cine radiography revealed disturbed oesophageal motility which disappeared after injection of the dopamine receptor agonist apomorphine. It is suggested that central dopaminergic abnormalities may be important in the aetiology of "off period belching."

Aged

A double-blind, controlled study of high-dose L-deprenyl in the treatment of Parkinson's disease.

The conventional dose of deprenyl used in Parkinson's disease is 10 mg/day, having been established by in vitro platelet studies and clinical evaluation. Twelve patients with Parkinson's disease on treatment with L-dopa who showed evidence of wearing-off effects or motor oscillation were studied in a double-blind, placebo-controlled, crossover trial to compare conventional doses of deprenyl with higher doses (up to 40 mg/day) and placebo. We did not find higher doses of deprenyl to be superior to conventional doses and in 17% of cases treatment had to be withdrawn because of side effects.

Adjuvants, Pharmaceutic

Levodopa peripheral pharmacokinetics and duration of motor response in Parkinson's disease.

To assess the relative influence of central pharmacodynamic and peripheral pharmacokinetic factors on the duration of motor response to levodopa, the relationship between motor function and plasma levodopa levels was studied in 31 Parkinsonian patients. Duration of benefit from single levodopa doses while fasting depended on the degree to which the plasma levodopa level had declined over four hours; wearing off occurred when the plasma levodopa level had fallen to approximately 50% of peak concentration, irrespective of the duration of the motor response. Whilst the amplitude of motor response to levodopa is likely to be modified by alternations in dopamine receptor stimulation and sensitivity as the disease progresses, it is proposed that the duration of response is primarily determined by levodopa peripheral pharmacokinetics rather than by central pharmacodynamic factors associated with dopamine storage capacity.

Administration, Oral

The effects of oral protein on the absorption of intraduodenal levodopa and motor performance.

Four patients with levodopa induced fluctuations in motor performance were studied during the constant intraduodenal infusion of levodopa. The results confirm that steady plasma levodopa levels with stable motor control can be achieved. However, when patients were given oral protein loads, motor performance declined despite maintenance of plasma levodopa levels. These findings suggest that competition for levodopa carrier mediated transport by amino acids, is more important at the blood-brain barrier than across the gut mucosa; thereby possibly limiting the efficacy of long-term direct intraduodenal administration of levodopa.

Aged

Pure RBC aplasia and myasthenia gravis. Coexistence of two diseases associated with thymoma.

Pure RBC aplasia (PRCA) and myasthenia gravis (MG) are occasionally associated with thymoma, although the occurrence of all three in a single patient is rare. We describe a patient in whom PRCA and MG occurred in conjunction with the presence of serum autoantibodies, evidence for a serum inhibitor of erythropoiesis, and elevation of circulating thymosin alpha 1. Although a thymoma could not be detected before death, postmortem examination of the mediastinum found scattered cells within a nodule, suggestive of a lymphoepithelial thymic neoplasm.

Aged

Criteria for fibular sesamoidectomy in hallux abducto valgus correction.

Fibular sesamoidectomy is necessary in certain instances to achieve permanent correction of hallux abducto valgus deformities. The decision to remove the fibular sesamoid is usually based on the position of the tibial sesamoid (which is determined by clinical and radiographic examination). If the fibular sesamoid is in positions 4 to 7, it is difficult, if not impossible, to maintain the correction of the hallux abducto valgus; if the position is 1 through 3, the sesamoids can be moved medially and maintained by the crista which is still intact.

Hallux