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Biomedical subjects

Stefano Ruggieri

Publications and source records attributed to Stefano Ruggieri.

22 records · Page 2Linked to original sources

Prospective randomized trial of lisuride infusion versus oral levodopa in patients with Parkinson's disease.

Motor complications are a major source of disability for patients with advanced Parkinson's disease. Surgical therapies provide benefit to some, but these treatments are expensive and associated with adverse effects. Current research indicates that motor complications are associated with abnormal, intermittent, pulsatile stimulation of denervated dopamine receptors using short acting dopaminergic agents such as levodopa. Retrospective studies suggest that the use of longer-acting more continuous dopaminergic therapies can improve both motor fluctuations and dyskinesia. We performed a prospective, long-term (4-year) trial comparing patients randomized to receive subcutaneous infusion of the dopamine agonist lisuride versus conventional therapy with oral levodopa and dopamine agonists. We demonstrate that patients receiving lisuride infusions experienced a significant reduction in both motor fluctuations and dyskinesia compared with patients receiving standard dopaminergic therapies. Benefits persisted for the 4-year duration of the study. Mean Unified Parkinson's Disease Rating Scale scores in "ON" and "OFF" states did not significantly change between baseline and 4 years for patients in the lisuride group, but deteriorated in patients in the levodopa group. This study indicates that continuous lisuride infusion can be beneficial for patients with advanced Parkinson's disease and reverse established motor fluctuations and dyskinesia.

Administration, Oral↗

Apomorphine infusion and the long-duration response to levodopa in advanced Parkinson's disease.

The authors investigated the long-duration response to levodopa in advanced Parkinson's disease. Eight patients with advanced Parkinson's disease disabled by severe ON/OFF fluctuations treated by chronic daytime subcutaneous apomorphine infusion with supplemental oral levodopa were studied. On day 1, oral levodopa was withdrawn at 4:00 pm and on the following morning subcutaneous apomorphine infusion was continued at the same rate without levodopa therapy. While receiving apomorphine alone, seven of the eight patients turned ON, and their usual dyskinesias returned. The ON phase persisted for 60 to 100 minutes (mean, 185.7 minutes) but then, despite continued, constant-rate apomorphine infusion to stabilize plasma levels, switched to an OFF phase. The authors conclude that the clinical effect of apomorphine is sustained by levodopa long-duration response. This effect is probably the result of postsynaptic mechanisms. In patients with advanced Parkinson's disease, the long-duration response to levodopa is present although slightly diminished.

Administration, Oral↗

Variation in the dopaminergic response during the day in Parkinson disease.

OBJECTIVE: In many parkinsonian patients with fluctuating disease the early morning levodopa dose is more effective than the following dose on the same day. In this study we investigated whether the poor responsiveness to the early afternoon dose of levodopa depends only on peripheral and central levodopa pharmacokinetics or also on pharmacodynamic factors. METHODS: Ten parkinsonian patients experiencing postprandial drug-resistant off periods received two boluses of apomorphine by subcutaneous injection at 8 am and 3 pm on two nonconsecutive days. On day 2, therapy was stopped at 11 am. For each bolus we determined time to on, duration of the on state, magnitude of benefit, and levodopa and apomorphine plasma levels at baseline and immediately after patients reached the on state. RESULTS: The mean duration of on phases was significantly shorter and the apomorphine plasma level needed to reach the on state was significantly higher in the afternoon than in the morning (P<0.01 by paired t test). CONCLUSIONS: This study suggest that there is a change in responsiveness to dopaminergic stimulation during the day. The less effective dopaminergic response in afternoon depends on pharmacodynamic factors and not only on peripheral and central levodopa pharmacokinetic.

Aged↗

Is there a role for uridine and pyrimidine nucleosides in the treatment of vascular dementia?

In the 70s, the discovery of a constant loss of acetylcholine (Ach) in the brains of people suffering from dementia led to the development, in order to improve cognitive functions, of drugs that increased Ach levels. The possibility that loss of a given neurotransmitter might be associated with the onset of a specific neurological syndrome led to suggestions that, as had already been found in Parkinson's disease, replacement therapy might drastically improve the course of the syndrome. We are now aware of the limits of this therapeutic approach. In this review, we analyse potential factors contributing to the partial failure of Ach replacement therapy, contrasting common beliefs regarding the Ach synapse with the difficulties in restoring its activity through replacement drugs. Considering the search for alternative strategies, in the second part of the review, we overview progress of research into pyrimidine compounds, now emerging as a new modulatory system acting through specific pyrimidino-receptors involved in various steps of cell signalling. Pyrimidine nucleosides might be useful in the chronic treatment of cognitive deficits resulting from vascular dementia.

Acetylcholine↗