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Biomedical subjects

O Rascol

Publications and source records attributed to O Rascol.

At least 181 records · Page 10Linked to original sources
PubMed1984

Should dopamine agonists be given early or late in the treatment of Parkinson's disease?

The long term consequences of the use of a dopamine agonist, bromocriptine, in the treatment of Parkinson's disease are reported. In a first study in 82 patients showing late side effects of levodopa, bromocriptine permitted a significant decrease of the gastro-intestinal adverse effects. In contrast, no significant improvement of end of dose deterioration from levodopa was noted. In cases where levodopa had ceased to be active, bromocriptine produced an improvement in the clinical state. The drug was ineffective in the very advanced stages of the disease or in the cases of dyskinesias without "on-off" effects. Bromocriptine did not significantly improve freezing or "on-off" effects, but reduced other side effects of levodopa, in particular dystonia. In a second group of 29 patients who had never received levodopa treatment, bromocriptine was shown to be very effective as a first treatment of the disease. The most important finding was the absence of long term side effects similar to those usually observed under levodopa: in this group and in comparison with 38 patients taking levodopa, dyskinesia, dystonia, oscillations in performance and especially "on-off" effects were not noted. However, a partial loss of efficacy of bromocriptine was observed in 27% of cases. In a third group of 10 patients, bromocriptine introduced according to a low and slow protocol was found to be active in limited number of patients only.

Adult↗
PubMedDate not supplied

Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial.

BACKGROUND: Rasagiline mesylate is a novel drug for Parkinson's disease with selective, irreversible monoamine oxidase B (MAO-B) inhibitor activity, and is effective as monotherapy in early disease. This study investigated rasagiline efficacy and safety in levodopa-treated patients with Parkinson's disease and motor fluctuations. METHODS: In an 18-week, double-blind, multicentre (74 hospitals and academic centres in Israel, Argentina, and Europe) trial, 687 outpatients were randomly assigned to oral rasagiline (231 individuals; 1 mg once daily), entacapone (227; 200 mg with every levodopa dose), or placebo (229). Primary outcome was change in total daily off-time (intention-to-treat population). Other measures included the clinical global improvement (CGI) score and unified Parkinson's disease rating scale (UPDRS) scores. Analysis was by intention to treat. FINDINGS: 88 (13%) patients who were assigned treatment did not complete the study (23 rasagiline, 30 entacapone, 35 placebo), mainly because of withdrawal of consent (n=34) and adverse events (n=34). Both rasagiline and entacapone reduced mean daily off-time (-1.18 h rasagiline and -1.2 h entacapone vs placebo -0.4 h; p=0.0001, p<0.0001, respectively) and increased daily on-time without troublesome dyskinesia (0.85 h vs placebo 0.03 h; p=0.0005 for both). We recorded significant mean improvements in CGI scores (-0.86 rasagiline and -0.72 entacapone vs -0.37 placebo; p<0.0001, p=0.0002, respectively). Changes in UPDRS scores also significantly improved for activities of daily living during off-time (-1.71 and -1.38 vs placebo; p<0.0001, p=0.0006, respectively) and motor function during on-time (-2.94 and -2.73 vs placebo; both p<0.0001). Frequency of adverse events was similar for all treatments. INTERPRETATION: Once-daily rasagiline reduces mean daily off-time and improves symptoms of Parkinson's disease in levodopa-treated patients with motor fluctuations, an effect similar to that of entacapone.

Administration, Oral↗
PubMedDate not supplied

A pharmacoeconomic evaluation of botulinum toxin in the treatment of spasmodic torticollis.

We performed a prospective study in 21 patients to evaluate the cost of treatment of spasmodic torticollis (cervical dystonia) before and after botulinum toxin type A (BTA) treatment and to assess the impact of BTA treatment on quality of life. Data were recorded for the analysis over a period starting 8 months before and ending 7.2 +/- 0.2 months (mean +/- SEM) after the first injection of BTA. All patients received at least two BTA injections (2.9 +/- 0.2 injections per patient). We studied direct medical costs (drugs, outpatient and inpatient visits, diagnostic procedures, physiotherapy), clinical effects of BTA (clinical rating scale and patient's global assessment), quality of life (French version of the Nottingham Health Profile [NHP]), and adverse reactions. Costs associated with the treatment of spasmodic torticollis before the first BTA injection were 479 +/- 143 French Francs (FF)/patient/month (97 +/- 29 US $/pt/mo). During BTA treatment, costs were 1,126 +/- 147 FF/pt/mo (228 +/- 30 US $/pt/mo), including a mean cost of BTA of 771 +/- 131 FF/pt/mo (157 +/- 27 US $/pt/mo). Treatment with BTA significantly decreased clinical symptoms of spasmodic torticollis and improved the emotional, social, and pain-related domains of the quality of life assessment. Botulinum toxin type A treatment increases the cost of treating spasmodic torticollis but improves quality of life in terms of pain, social, and psychologic functioning in patients with spasmodic torticollis.

Adult↗
PubMedDate not supplied

Adverse drug reactions to selegiline: a review of the French pharmacovigilance database.

The present pharmacoepidemiologic study was performed to characterize the profile of adverse drug reactions (ADRs) reported with selegiline, a monoamine oxidase B (MAO-B) inhibitor used in the treatment of Parkinson's disease and previously reported to induce an excess of mortality. The analysis was performed with use of the French Pharmacovigilance Database between 1989 and 1997. This database includes all ADRs reported by French practitioners (and especially "serious" and "unexpected" ADRs). Three different analyses were performed: identification of ADRs reported with selegiline, comparison with the ADR profile observed with other antiparkinsonian drugs, and a case/non-case study investigating the occurrence of cardiovascular ADRs with selegiline in comparison with other drugs in general and other antiparkinsonian drugs (e.g., levodopa [L-Dopa], dopamine agonists) in particular. The most often reported ADRs with selegiline were psychiatric (delirium, hallucinations, agitations), cardiovascular (orthostatic hypotension, arterial hypertension, etc.) and neurologic (sedation, abnormal movements, etc.). Psychiatric and cardiovascular ADRs were more frequently reported with selegiline than with L-Dopa or dopamine agonists. The case/ non-case study found an increased risk of cardiovascular ADRs (OR = 1.72; 95% Cl = 1.16-2.55)when selegiline was associated with L-Dopa. These data show that the profile of selegiline-induced ADRs differs from that of other antiparkinsonian drugs (L-Dopa, dopamine agonists) with more psychiatric and cardiovascular ADRs. We suggest that the higher frequency of cardiovascular ADRs could explain, at least partially, the previously reported increase in mortality rate.

Adverse Drug Reaction Reporting Systems↗
PubMedDate not supplied

Sleep attacks and antiparkinsonian drugs: a pilot prospective pharmacoepidemiologic study.

A prospective survey was performed to characterize the prevalence of sleep attacks and to evaluate precipitating factors in a group of 236 patients with idiopathic Parkinson's disease. Sleep attacks were reported by 72 patients (30.5%). Multivariate analysis showed a marked association between the occurrence of sudden sleep episodes and first autonomic failure, followed by treatment with ropinirole and bromocriptine. The present work underlines the major contributing role of autonomic failure followed by dopamine agonists in the occurrence of such an event. Because a relationship between sleep attacks and not only ropinirole but also bromocriptine treatment was described, the present work suggests that sleep attacks are a common side effect of all dopamine agonists.

Aged↗
PubMedDate not supplied

Dyskinesia: L-dopa-induced and tardive dyskinesia.

Neuroleptic induced tardive dyskinesia and L-dopa-induced dyskinesia are the two most common types of drug-induced abnormal involuntary movements. These two drug-induced dyskinesias are clearly different with respect to the offending drugs and the underlying disease, but they both share a number of intriguing similarities in terms of clinical phenomenology, epidemiology, risk factors, pathophysiological mechanisms and therapeutic responses. In both instances, it is believed that some dysregulation occurring at the level of the striatal dopaminergic receptors, and related non-dopaminergic neurotransmitters systems are playing a crucial role in the development and persistence of the mechanisms causing dyskinesia. These long-lasting functional changes, known as the "priming" phenomenon, are responsible for an impaired balance within the relays of the cortico-subcortical motor loops that release an inadequate output from the basal ganglia leading to an abnormal motor behavior. From a therapeutic perspective, there are also many similarities in the strategies proposed to manage these two dyskinesias. In both cases, unprimed patients not previously exposed to the offending drugs, are offered alternative medications to reduce, at least partly, the risk of occurrence of future dyskinesia: "atypical" neuroleptics in the place of "typical" neuroleptics, and dopamine agonists in the place of L-dopa. In both cases, once dyskinesias are present, in already "primed" patients, both types of dyskinesia appear to be poorly and only partly reversible. Based on limited clinical evidence, it is a common proposal to switch the dyskinetic subject from "typical" to "atypical" neuroleptics for tardive dyskinesia, or to switch from (or more pragmatically to substitute as much as possible) L-dopa to a dopamine agonist for L-dopa-induced dyskinesia. In both cases, efficacious symptomatic antidyskinetic interventions, to reduce the severity of a ready present dyskinesia, are rare. There are some uncontrolled data suggesting that dopamine depleting agents, like tetrabenazine, are possibly useful for tardive dyskinesia; however, there is more clinical evidence to support the efficacy of amantadine and functional surgery in parkinsonian patients with L-dopa-induced dyskinesia.

Antiparkinson Agents↗
PubMedDate not supplied

L-Dopa-induced sedation: a double-blind cross-over controlled study versus triazolam and placebo in healthy volunteers.

Incidental case reports suggest that some parkinsonian patients treated with dopaminergic drugs complain of drowsiness but few controlled data are available. We compared the sedative effects of L-Dopa (200 mg + 50 mg benserazide, PO), triazolam (0.125 mg) and placebo in a randomized double-blind cross-over design in 22 healthy volunteers pretreated with domperidone (60 mg/day). Drowsiness was assessed using a visual analog scale (VAS), a computerized choice reaction time test (CRT) and an electro-oculogram (EOG). L-Dopa and triazolam induced significant drowsiness, compared to placebo, on VAS, CRT and some EOG parameters. After this first evaluation session, all subjects were chronically treated for 11 days with 600 mg/d of L-Dopa. Drowsiness induced by L-Dopa, triazolam or placebo was then tested again on three consecutive days to assess putative dopaminergic tolerance. After chronic L-Dopa treatment, triazolam-induced sedation remained unchanged while L-Dopa sedative effects were no longer significant except on the VAS, preventing the conclusion that tolerance occurred. These data suggest that an acute dose of L-Dopa induces sedation in L-Dopa-naive subjects. This sedative effect must be considered in clinical practice and when studying the effects of L-Dopa on motor or neuropsychological performance, especially in acute tests.

Adult↗
PubMedDate not supplied

A study of salivary secretion in Parkinson's disease.

Hypersialorrhea is frequently reported in patients with idiopathic Parkinson's Disease (PD). Excessive production of saliva, swallowing difficulties, or both could explain this complaint. Dopamine (DA) has been shown to modulate salivary secretion in a number of vertebrate and invertebrate species. The present study was performed to compare the unstimulated salivary flow in 83 patients with PD (8 untreated and 75 treated with levodopa + DA agonist) and in 65 age- and sex-matched control subjects. The Mann-Whitney U-test showed a significantly lower salivary flow in treated patients with PD (535 +/- 42 mg/2 min) (p < 0.002) and de novo patients (447 +/- 141) (p < 0.03) compared to controls (834 +/- 68 mg/2 min) with no relation with age or sex. Finally, the present study of reduced salivary flow in PD suggests that complaints of hypersialorrhea are not caused by a salivary defect, but could be explained by difficulties in swallowing. The decrease in salivary flow could be explained by autonomic dysfunction in PD.

Adult↗
PubMedDate not supplied

Disease modifying trials in Alzheimer disease: methodological and statistical issues.

In order to establish that a drug has an impact on disease progression, a clinical trial must study both the symptomatic and the disease modifying effect of the drug. Disease modifying trials raise some methodological issues with regard to the choice of the design (parallel arm versus two- period design), of the outcome (clinical versus surrogate) and of the statistical analysis (management of missing data).

Alzheimer Disease↗
PubMedDate not supplied

[Pharmacovigilance of antibiotics. Evaluation by the Midi-Pyrénées Pharmacovigilance Center between 1989 and 1992].

The present retrospective study investigates the antibiotic-induced side effects in a regional French Pharmacovigilance Center between 1989 and 1992. Five-hundred and seventy six side effects were reported, involving 611 drugs and accounting for 18% of the total activity of the pharmacovigilance center. Most of the side effects involved penicillins and systemic quinolones followed by sulfonamides, cephalosporines and glycopeptides. When expressed in number of adverse effects in Defined Daily Dose, the maximal frequency of side effects was observed with sulfonamides. In contrast, the frequency of penicillin-induced adverse events was low. The most frequently reported side effects were cutaneous and/or immunologic (54%) and digestive (24%) disturbances. Among serious side effects, 3 toxic epidermal necrolysis (2 with cotrimoxazole), 16 pseudomembranous colitis (11 with beta-lactam antibiotics, 4 with macrolides and lincomycines and 1 with vancomycin), 14 neuropsychiatric reactions (seizures, confusions and hallucinations with beta-lactam antibiotics and fluoroquinolones) were notified. Five antibiotic-induced side effects led to the death.

Adverse Drug Reaction Reporting Systems↗
PubMedDate not supplied

[Movement disorders induced by drugs: experience at a pharmaco-vigilance center over five years].

The present retrospective study investigates the characteristics of drug-induced movement disorders notified to a Regional Drug Surveillance Centre. Among 4000 general side effects spontaneously reported to the Centre between 1989 and 1993, 122 were drug-induced movement disorders. Drug-induced parkinsonism (40 per cent) was mainly due to antidopaminergic agents (neuroleptics but also antiemetics or calcium channel blockers). Acute dyskinesia and dystonia (25 per cent) as well as tardive dyskinesia (14 per cent) involved mainly neuroleptics or antiemetics. Non-parkinsonian tremors (11 per cent) were related mostly to tricyclic antidepressants. Involvement of other less often suspected drugs (non-imipramine antidepressants, cardiac or hypolipidaemic drugs, etc) is discussed.

Adult↗