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Biomedical subjects

F Stocchi

Publications and source records attributed to F Stocchi.

At least 55 records · Page 3Linked to original sources
PubMed1997

Low dose of clozapine in the treatment of dopaminergic psychosis in Parkinson's disease.

Dopaminergic psychosis frequently complicates the pharmacological treatment of Parkinson's disease. Dose reduction of dopaminomimetic therapy or treatment with conventional neuroleptics improves psychosis but worsens parkinsonism. In an open-label 12-month trial, the clinical antipsychotic efficacy of the atypical neuroleptic clozapine was investigated in 36 parkinsonian patients (age range 46-85 years) with symptoms of dopaminergic psychosis including delusions, vivid dreams, hallucinations, frank paranoid delirium, and hypersexuality. Clozapine, given orally at bedtime, was started at a dose of 6.25 mg and titrated upward to the minimal effective dose. In all patients, psychosis responded to very low clozapine doses (mean 10.59 +/- 6.48 mg/day). Clozapine doses correlated with the severity of psychosis. During clozapine treatment, parkinsonian disabilities and levodopa dosage remained statistically unchanged. During the 12-month study, no patient had clozapine-induced agranulocytosis or other severe side effects. These findings indicate that even at low doses, clozapine effectively controls dopaminergic psychosis in Parkinson's disease patients without compromising motor function.

Aged↗
PubMed1997

The long-duration action of levodopa may be due to a postsynaptic effect.

A single dose of levodopa (L-DOPA) reduces motor disability in Parkinson's disease (PD) for a few hours, a short-duration effect. However, there are suggestions that L-DOPA may also produce a long-duration benefit of some days. In the present study, we examined the long-duration action of L-DOPA by observing the time taken to achieve maximum stable benefit after starting a constant dose of sinemet-CR (sinemet-CR) (200 g L-DOPA/50 mg carbidopa) twice daily in nine newly diagnosed patients, and the time taken to deteriorate back to baseline after stopping treatment. A single dose of sinemet-CR (200 mg L-DOPA/50 mg carbidopa) had little obvious short-duration action on the Unified PD Rating Scale (UPDRS) motor scores in the majority of patients, either before starting chronic sinemet-CR therapy (200 mg L-DOPA/50 mg carbidopa, b.i.d.) or after chronic treatment. However, all patients gradually improved on chronic sinemet-CR therapy, taking 9.3 +/- 1.8 days to achieve maximum response. On stopping chronic sinemet-CR treatment, it took 6.8 +/- 3.0 days for the same patients to deteriorate back to baseline motor disability. In similar experiments, the time taken to deteriorate back to baseline after stopping treatment with the directly acting dopamine agonist ropinirole (9-21 mg daily) in eight other de novo patients with PD was found to be 6.2 +/- 1.7 days. The long-duration effect of L-DOPA and ropinirole may, therefore, be due to some slowly evolving postsynaptic pharmacodynamic change in the central nervous system (CNS). Loss of this long-duration action may be responsible for the emergence of motor fluctuations on chronic L-DOPA therapy.

Adult↗
PubMed1997

Urodynamic and neurophysiological evaluation in Parkinson's disease and multiple system atrophy.

AIMS: To determine whether Parkinson's disease and multiple system atrophy each has a distinct pattern of micturition abnormalities and whether a urodynamic evaluation could be useful in the differential diagnosis between the two diseases. METHODS: Sixty two patients (30 with Parkinson's disease and 32 with multiple system atrophy) underwent a complete urodynamic evaluation and neurophysiological testing. RESULTS: Of the parkinsonian patients 36.6% had normal micturition findings with normal bladder sensitivity; 26.7% had delayed or incomplete pelvic floor relaxation; 26.7% had hyperreflexia with vesicosphincteric synergy; and 10% had hyperreflexia with vesicosphincteric synergy associated with incomplete pelvic floor relaxation. Parkinsonian patients with a normal urodynamic pattern had significantly less severe disease and a shorter duration of disease in years than those who had abnormal patterns. Patients with hyperreflexia had significantly higher severity of disease. All the patients with multiple system atrophy had hyperreflexia with synergy. Two urodynamic patterns were identified: hyperreflexia with vesicosphincteric synergy (90.6% of patients), and hyperreflexia with vesicosphincteric synergy and incomplete pelvic floor relaxation (in 9.4%). Hyperreflexia with synergy correlated neither with the severity nor with the duration of disease. Sphincter EMG analysis showed that all the parkinsonian patients had normal sphincter EMG whereas 24 of the 32 patients with multiple system atrophy had neurogenic signs. CONCLUSIONS: Urodynamic evaluation and sphincter EMG are both useful tests in the differential diagnosis between Parkinson's disease and multiple system atrophy. Urodynamic findings may be abnormal before patients with multiple system atrophy reach an advanced stage of the disease. Recordings of EMGs from perineal muscles become abnormal as the disease progresses in multiple system atrophy but not in Parkinson's disease.

Aged↗
PubMed1996

Fluctuating parkinsonism: a pilot study of single afternoon dose of levodopa methyl ester.

Thirty-four patients with idiopathic fluctuating Parkinson's disease and early afternoon "delayed on" or severely resistant "off" periods, in spite of long-term antiparkinsonian therapy, were studied. The first afternoon levodopa administration was substituted with an equimolar dosage of the liquid formulation levodopa methyl ester (LDME). The major end-points for efficacy were latency to "on" and duration of "on" periods. The patients were divided into five subgroups according to their baseline treatment and they were evaluated monthly for 6 months using the Unified Parkinson's Disease Rating Scale. The patients completed weekly self-evaluation using an "on-off" chart. LDME was well tolerated by all the patients. A statistically significant reduction in latency to "on" was observed in all patients. The clinical effect of LDME remained stable during the treatment period (repeat measures ANOVA). The more rapid clinical effect of LDME and its stable and predictable antiparkinsonian activity represents a new and useful approach for treating patients with complicated Parkinson's disease.

Administration, Oral↗
PubMed1996

QT interval and QT dispersion in multiple system atrophy (Shy-Drager syndrome).

To evaluate the influence of autonomic function on the QT interval and QT dispersion, 18 patients (10 males and 8 females; mean age 61 +/- 9 years) with multiple system atrophy (MSA, Shy-Drager syndrome) were studied. Cardiovascular tests were performed to assess the degree of autonomic dysfunction. The QT interval, corrected QT (QTc), QT dispersion (QTd), corrected and adjusted QTd were calculated from a standard 12-lead electrocardiogram. Fifteen healthy subjects matched for sex and age were studied as controls. Nine MSA patients showed severe autonomic dysfunction with orthostatic hypotension. In the remaining patients definite autonomic impairment was found. No statistically significant difference was found in QTd and only a trend towards higher values of maximal QTc was found in patients compared with controls. QTc prolongation, defined as greater than the mean +/- 2 SD of the controls, was detected only in three out of the 18 MSA patients (17%). No correlation was found between the severity of autonomic impairment and repolarization parameters. Our data suggest that chronic autonomic impairment in patients with MSA does not significantly affect ventricular repolarization and ventricular dispersion.

Adult↗
PubMed1996

A pharmacological study of cocaine activity in planaria.

Planaria has been proposed as a suitable research model in neurobiology because of its relatively simple organization. Dopaminergic agonists induce in this flatworm typical hyperkinesias that can be antagonized by dopaminergic blocking agents. The neurochemical basis of the effects of cocaine in vertebrates has not been fully elucidated, but the inhibition of catecholamine reuptake at a presynaptic level seems to play an important role. In this study we analyzed the involvement of the dopaminergic system in the mechanism of action of cocaine in planaria. The dose-related effects of cocaine on planaria motility and the response to cocaine treatment associated with the administration of specific D1 or D2 dopamine agonists and antagonists were investigated. The effects of reuptake inhibitors on cocaine activity were also studied. Planaria specimens treated with low doses of cocaine become motionless, whereas high doses induce a typical behavioural response, identical to the response induced by specific D2 agonists. This response is inhibited by a D2 selective blocking agent. Nomifensine, a specific dopamine reuptake inhibitor, induces a mixed D1/D2 response. The results of these experiments are discussed, also in relation with the conservation of dopaminergic receptors during evolution.

Amidines↗
PubMed1996

Motor fluctuations in levodopa treatment: clinical pharmacology.

Fluctuations in motor performance and dyskinesias are a common problem in the long-term management of Parkinson's disease. The pharmacokinetics and the pharmacodynamics of levodopa, loss of presynaptic dopamine terminals, alterations in postsynaptic dopamine receptor sensitivity, or changes in the modulatory influences of nondopaminergic transmitter system could play a pathogenic role. The short half-life of levodopa and its absorption and transport are important factors. The pharmacodynamic response to levodopa changes during long-term therapy. An absolute threshold in plasma levodopa level, below which the patients are off, appears. The patients show a therapeutic window for levodopa which becomes narrower with time. This therapeutic window can be widened by giving continuous infusion of dopaminergic drugs. Motor fluctuations can be ameliorated by a more physiological continuous stimulation of the receptor site and by avoiding repeated shifting in levodopa levels. Long-term complications are attenuated by an early combination of levodopa with dopamine agonist.

Antiparkinson Agents↗
PubMed1995

The bereitschaftspotential preceding stepping in patients with isolated gait ignition failure.

The cerebral activity preceding voluntary, self-paced ankle dorsiflexion movements while seated was compared with that before a stepping movement of the same foot while standing in four patients with isolated gait ignition failure. Results within the patients group were variable, but all exhibited some increase in the Bereitschaftspotential (BP) amplitude when stepping as compared with sitting, similar to that seen in normal subjects. This differs from previous results in patients with Parkinson's disease in which stepping was not accompanied by a normal increase in BP amplitude. This difference suggests that the mechanisms responsible for the start hesitation that is common to both Parkinson's disease and gait ignition failure may differ in the two conditions.

Aged↗
PubMed1995

Ambulatory blood pressure monitoring and cardiovascular function tests in multiple system atrophy.

Cardiovascular tests (CT) of autonomic function and non-invasive ambulatory blood pressure (BP) and heart rate (HR) monitoring were performed in 17 patients with multiple system atrophy (MSA) (mean age 61 +/- 9 years) and in 12 healthy subjects matched for sex and age. CT showed severe autonomic dysfunction with orthostatic hypertension (OH) in eight patients with MSA (47%) (Group I). The remaining nine out of the 17 patients didn't show BP abnormalities during CT but an impaired HR reflex response was found (Group II). BP monitoring showed a reversed circadian BP rhythm in Group I with higher night-time than day-time values, a blunted circadian BP pattern in Group II and a normal day-night BP reduction in controls. Day-night HR reduction was poor in Group II and absent in Group I. Post-prandial hypotension was evaluated after a standard meal. In Group I systolic/diastolic BP fell within 30 minutes after meal (from 135 +/- 16/89 +/- 13 to 118 +/- 17/73 +/- 12 mmHg; p < 0.05) and after two hours had not returned to basal levels. In Group II a reduction of only systolic BP was found within 45 minutes after meal and persisted for one hour. OH clinically identifies a subgroup of MSA patients with a more severe BP dysregulation characterized by severe post-prandial hypotension and reversed circadian BP rhythm. CT and ambulatory BP monitoring are useful tools in identifying early stage of cardiovascular autonomic impairment.

Adult↗
PubMed1995

Differential diagnosis of parkinsonism.

The diagnosis of idiopathic Parkinson's disease (PD) is essentially clinical and is reached by exclusion. An akinetic rigid syndrome frequently means PD, although a number of other neurodegenerative diseases can share bradykinesia, rigidity, postural instability, and sometimes tremor. Parkinsonism can be classified as follows: degenerative, metabolic, vascular, iatrogenic, toxic, infectious, traumatic, and secondary to mass effect. The diagnostic approach are discussed.

Atrophy↗
PubMed1994

Analysis of repetitive and nonrepetitive sequential arm movements in patients with Parkinson's disease.

We examined the motor performance of Parkinson's disease patients and normal subjects during nonrepetitive and repetitive sequential tasks. Parkinson's disease patients took longer than normal subjects to complete the nonrepetitive task, the sequential drawing of a pentagon. In patients, movement times lengthened as the sequence neared completion. The amount of lengthening was similar in nonrepetitive and repetitive tasks (sequential alternating drawing of each side of the pentagon). In parkinsonian patients the slowing at the end of the sequential tasks does not appear to be influenced by whether the sequential task involves nonrepetitive or repetitive movements.

Adult↗
PubMed1994

Comparison between a fast and a slow release preparation of levodopa and a combination of the two: a clinical and pharmacokinetic study.

After overnight drug withdrawal and in the fasting state, 11 patients with Parkinson's disease (PD) and a fluctuating response to chronic levodopa treatment were given, in random sequence on consecutive days, equivalent levodopa doses (with peripheral decarboxylase inhibitor) (a) as levodopa methyl ester (ME), (b) as Sinemet CR, or (c) as half the dose of ME together with a halved tablet of Sinemet CR. All patients turned ON rapidly after treatments a and c, but only half did so after treatment b. On period duration was longest after treatment c, intermediate after treatment a, and shortest after treatment b. Pharmacokinetic analysis in a subset of 6 patients revealed no significant difference between treatments a and c, although there was a trend for t1/2 to be longer after treatment c. We conclude that giving ME with a halved tablet of Sinemet CR provided a useful clinical balance between rapid onset and extended duration of action of at least the first levodopa intake of the day. In view of differing release profiles between whole and halved tablets of Sinemet CR, similar single-dose pharmacokinetic studies, followed by sequential-dose clinical studies, are indicated when Sinemet CR 125 tablets soon become available.

Aged↗
PubMed1994

Clinical implications of sustained dopaminergic stimulation.

Fluctuations in motor performance are the major problems in chronic management of Parkinson's disease. Most of these fluctuations reflect the decline of levodopa availability. As a consequence, levodopa dosage might be increased and the interdose interval progressively shortened. The postsynaptic dopamine receptors at this point are exposed to a nonphysiologic shift in dopamine level, which may induce changes at the receptor site and contribute to the appearance of "on-off" phenomena and dyskinesias. We compared a group of 18 patients treated for 60 consecutive months with continuous subcutaneous lisuride infusion with a group of 20 patients treated with conventional oral levodopa treatment. The clinical evaluations performed during the study showed in the lisuride group only a worsening of dyskinesias, whereas the other symptoms remained unchanged. In the other group the evaluation scores showed a significant worsening of all long-term treatment complications. The slow-release preparations of levodopa may ensure a more continuous dopaminergic stimulation than standard formulations. However, the use of these compounds is difficult in severely fluctuating patients because the lack of a plasma peak level usually leads to a very long delay before patients turn "on." We studied the pharmacokinetic and clinical effects of the two slow-release preparations of levodopa [Madopar HBS and Sinemet controlled-release (CR)] and a combination of Sinemet CR plus standard Sinemet in 13 fluctuating parkinsonian patients. The results of this study show that the combination of standard Sinemet and Sinemet CR ensures a more prolonged clinical effect with a very short latency to the "on" phase.

Aged↗
PubMed1993

The Bereitschaftspotential preceding simple foot movement and initiation of gait in Parkinson's disease.

We compared the Bereitschaftspotential preceding a simple foot movement while sitting and a stepping movement while standing in a group of normal subjects and seven patients with mild to moderate Parkinson's disease (PD) while off medication. None had major difficulties stepping to initiate gait. Electromyographic signals from tibialis anterior triggered the averaging of electroencephalographic signals from the scalp. Bereitschaftspotential preceding a standing stepping movement were larger than those before a foot movement while sitting in normal subjects, but no difference was observed in patients with PD. The absence of an increase in the Bereitschaftspotential when stepping in PD may reflect an impairment of the preparation and assembly of the complex sequences of movement necessary to initiate walking, even in the early stages of the illness.

Adult↗