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Biomedical subjects

C Brefel-Courbon

Publications and source records attributed to C Brefel-Courbon.

At least 19 recordsLinked to original sources
PubMed2006

Sleep disruption, daytime somnolence and 'sleep attacks' in Parkinson's disease: a clinical survey in PD patients and age-matched healthy volunteers.

Recent case reports of 'sleep attacks' (SA) in patients with Parkinson's disease (PD) generated concerns about drug-induced daytime somnolence in this population. However, there are nearly no comparative data on sleep and vigilance problems between PD patients and normal controls. We performed a cross-sectional survey in PD patients and age-matched controls using a structured questionnaire on PD history, treatments, co-morbidity, activities of daily living, habits, exercise, sleep pattern, driving, pre-existing nocturnal problems, daytime somnolence, episodes of SA and the circumstances in which such episodes occurred. Daytime somnolence was also measured with the Epworth Sleepiness Scale (ESS) and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). 176 PD patients and 174 controls were included. The same proportion of PD patients (27%) and controls (32%) reported episodes of SA, but these were more frequent in PD patients and occurred more frequently during situations requiring attention (10.8% vs. 1.7%, p<10(-3)). More PD patients had abnormal daytime somnolence (ESS) and poor sleeping quality (PSQI). The most consistent factor associated with SA was the duration of levodopa therapy and the predictive value of an abnormal ESS score was rather poor (40.7%). Abnormal daytime somnolence and poor sleep quality at night are more frequent in PD patients than in normals. However, SA are reported in both groups, although less frequently in the normals during activities that requires attention.

Activities of Daily Living↗
PubMed2004

Intracellular ferritin accumulation in neural and extraneural tissue characterizes a neurodegenerative disease associated with a mutation in the ferritin light polypeptide gene.

Abnormal accumulation of ferritin was found to be associated with an autosomal dominant slowly progressing neurodegenerative disease clinically characterized by tremor, cerebellar ataxia, parkinsonism and pyramidal signs, behavioral disturbances, and cognitive decline. These symptoms may appear sequentially over a period of 4 decades. Pathologically, intranuclear and intracytoplasmic bodies were found in glia and subsets of neurons in the central nervous system as well as in extraneural tissue. Biochemical analyses of these bodies isolated from the striatum and cerebellar cortex revealed that ferritin light polypeptide (FTL) and ferritin heavy polypeptide (FTH1) were the main constituents. Molecular genetic studies revealed a 2-bp insertion mutation in exon 4 of the FTL gene. The resulting mutant polypeptide is predicted to have a carboxy terminus that is altered in amino-acid sequence and length. In tissue sections, the bodies were immunolabeled by anti-ferritin and anti-ubiquitin antibodies and were stained by Perls' method for ferric iron. Synthetic peptides homologous to the altered and wild-type carboxy termini were used to raise polyclonal antibodies. These novel antibodies as well as an antibody recognizing FTH1 immunolabeled the bodies. This study of this disorder has provided additional knowledge and insights in the growing area of ferritin-related neurodegeneration.

Adult↗
PubMed2003

Deep brain stimulation for parkinson's disease: correlation between intraoperative subthalamic nucleus neurophysiology and most effective contacts.

Though intraoperative neurophysiology is essential to precisely define the definitive target, little is known regarding its predictive value in defining the most effective contact for chronic deep brain stimulation. In this retrospective study, we reviewed the correlation between intraoperative neurophysiology and contacts selected for chronic stimulation. Twenty consecutive patients implanted for subthalamic nucleus (STN) stimulation were reviewed. There was no significant correlation between the electrophysiologically defined STN and the most effective contact for chronic stimulation at 3 months or at 6 months. Furthermore, there was a discrepancy between the most effective contact for rigidity versus akinesia or tremor at 3 months. Interestingly, at 3 months, the same electrode contact was maximally efficient for rigidity, akinesia and tremor in only 13 of the 39 cases. This lack of correlation did not affect the global improvement.

Adult↗
PubMed2002

The management of patients with early Parkinson's disease.

A major problem in the management of early Parkinson's disease is to choose the first medication to prescribe. This decision should rely on the level of available clinical evidence, largely based, at least for efficacy, on the results of randomised clinical trials. Safety and costs are also crucial to consider. Other factors like for example pathophysiological concepts, individual experience, marketing pressure, socio-economical environment, patients needs and expectations have, however, also their own influence. Levodopa is efficacious and cheap, but induces long-term motor complications. The early use of dopamine agonists is more and more frequently promoted, because large prospective L-dopa-controlled trials demonstrated that this strategy reduces the risk of such long-term complications. Integrating individual clinical expertise to the best available external clinical evidence (evidence-based medicine) is the best strategy in making decisions about the care of individual patients.

Antiparkinson Agents↗
PubMed2001

Origin of the mutations in the parkin gene in Europe: exon rearrangements are independent recurrent events, whereas point mutations may result from Founder effects.

A wide variety of mutations in the parkin gene, including exon deletions and duplications, as well as point mutations, result in autosomal recessive early-onset parkinsonism. Interestingly, several of these anomalies were found repeatedly in unrelated patients and may therefore result from recurrent, de novo mutational events or from founder effects. In the present study, haplotype analysis, using 10 microsatellite markers covering a 4.7-cM region known to contain the parkin gene, was performed in 48 families, mostly from European countries, with early-onset autosomal recessive parkinsonism. The patients carried 14 distinct mutations in the parkin gene, and each mutation was detected in more than one family. Our results support the hypothesis that exon rearrangements occurred independently, whereas some point mutations, found in families from different geographic origins, may have been transmitted by a common founder.

Age of Onset↗
PubMed2001

Long-term mortality results of the randomized controlled study comparing bromocriptine to which levodopa was later added with levodopa alone in previously untreated patients with Parkinson's disease.

The present paper compares, in terms of mortality, two treatment regimens for Parkinson's disease (PD), i.e., bromocriptine later combined with levodopa versus levodopa only. Between 1982 and 1989, 60 PD patients (29 treated with levodopa alone [group D] and 31 receiving first bromocriptine followed by an association of bromocriptine + levodopa [group B/D]) were recruited. Data were updated in January 2000. Survival functions were estimated using Kaplan Meier product-limit method and comparison between the two groups with the log-rank test. Mortality was also compared with that of the general French population using standardized mortality ratios (SMRs). The mean duration of follow-up was 10.3 +/- 3.0 years. Seventeen patients died during the follow-up: nine in the group B/D and eight in the group D. The probability of survival at 10 years was 79.0% [95% confidence interval [CI]: 71.4-86.6] in group B/D and 72.9% [95% CI: 63.3-82.6] in group D. In comparison with the general French population, SMRs were not statistically different from 1, in the whole sample of PD patients (1.21, 95 % CI [0.71-1.95]), in group D (0.98 [0.42-1.93]), or in group B/D (1.53 [0.70-2.92]). In this population, we were unable to find any favourable effect of an early use of bromocriptine on mortality in PD in comparison with levodopa alone.

Aged↗
PubMed2001

Idazoxan, an alpha-2 antagonist, and L-DOPA-induced dyskinesias in patients with Parkinson's disease.

Dyskinesia is a frequent and disabling side effect in patients with Parkinson's disease treated with chronic dopa-therapy. Preclinical data in the 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) monkey suggest that alpha-2 antagonists may reduce dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. We assessed, in a pilot randomised placebo-controlled study, the effects of single oral doses (10 mg, 20 mg, and 40 mg) of idazoxan, an alpha-2 antagonist, on motor parkinsonian disability and L-DOPA-induced dyskinesia following an acute oral challenge of L-DOPA in 18 patients with Parkinson's disease. The severity of L-DOPA-induced dyskinesia improved after 20 mg idazoxan pretreatment, while there was no concommittant deterioration in the antiparkinsonian response to L-DOPA. These results suggest that blocking alpha-2 receptors in patients with Parkinson's disease might improve L-DOPA-induced dyskinesia without the cost of a return of parkinsonian symptomatology. Further studies are required to assess whether this property could have potential therapeutic applications in the long-term management of dyskinetic patients with Parkinson's disease.

Administration, Oral↗
PubMed2001

Amitriptyline treatment in chronic drug-induced headache: a double-blind comparative pilot study.

OBJECTIVE: To assess the effects of amitriptyline and sudden analgesic withdrawal on headache frequency and quality of life in patients suffering from chronic daily headache related to analgesics abuse. METHODS: Seventeen nondepressed patients with chronic drug-induced headache were included in a 9-week, parallel-group, randomized, double-blind, placebo-controlled study. After abrupt analgesic withdrawal, amitriptyline or an active placebo (trihexyphenidyl) was started. The primary efficacy variable was headache frequency recorded on a headache diary in the last 4 weeks of each treatment. The secondary efficacy variable was quality of life (Nottingham Health Profile). RESULTS: Headache frequency decreased by 45% in the amitriptyline group and by 28% in the trihexyphenidyl group. Amitriptyline enhanced all the dimensions of quality of life and significantly improved emotional reaction and social isolation. CONCLUSION: This pilot study suggests a beneficial effect of amitriptyline on headache frequency and quality of life for patients with chronic drug-induced headache.

Adult↗
PubMed2001

Orthostatic hypotension in patients with Parkinson's disease: pathophysiology and management.

Orthostatic hypotension is common in elderly patients, and is now considered to be an important prognostic factor for cognitive decline and mortality. In patients with Parkinson's disease, the prevalence of symptomatic orthostatic hypotension may be as high as 20%. Two factors could explain this high prevalence. First, dopaminergic drugs may induce or worsen orthostatic hypotension. Secondly, Parkinson's disease is a cause of primary autonomic failure with an involvement of the peripheral autonomic system as shown by the ubiquitous distribution of Lewy bodies and reduced iobenguane [metaiodobenzylguanidine (MIBG)] cardiac uptake. These pathological and pharmacological characteristics clearly differentiate autonomic failure of Parkinson's disease from multiple system atrophy. If autonomic abnormalities appear to be present from the first stage of the disease, early onset (within the first year) of symptomatic orthostatic hypotension in the course of parkinsonism can be considered as an exclusion criteria for idiopathic Parkinson's disease. No specific clinical trials have evaluated the effects of antihypotensive drugs in patients with Parkinson's disease and thus no specific therapeutic strategy can be recommended. The management of orthostatic hypotension in patients with Parkinson's disease should always start with patient education and nonpharmacological treatment. Drug therapy should be reserved for symptomatic patients who do not get benefit from nonpharmacological management. Among the available drugs, alpha1-adrenergic agonists (mainly midodrine) or plasma volume expanders (mainly fludrocortisone) are the most frequently used. There are also some drugs that are currently investigational such as yohimbine and droxidopa. Other drugs such as desmopressin or octreotide may be of interest in some situations. Domperidone is widely used in patients with parkinsonism with no proven effect on orthostatic hypotension.

Blood Volume↗
PubMed2000

Lack of autonomic nervous dysfunction in progressive supranuclear palsy, a study of blood pressure variability.

Blood pressure and heart rate variability were analyzed in eight patients with progressive supranuclear palsy in comparison with two control groups (10 healthy patients and 10 patients with multiple system atrophy). Blood pressure and heart rate were recorded using digital photoplethysmography with the patient in supine position and during a head-up-tilt test (70 degrees for 10 minutes). Spectral analysis was performed using fast Fourier transformation for 512 consecutive systolic blood pressure and heart rate values. The head-up-tilt test induced a significant increase in systolic blood pressure in patients with progressive supranuclear palsy and in healthy patients and a significant systolic blood pressure decrease in patients with multiple system atrophy. During the head-up-tilt test, low-frequency energy of systolic blood pressure (70-130 mHz) that reflected baroreflex-dependent sympathetic tone also increased in patients with progressive supranuclear palsy and in healthy patients. By contrast, in patients with multiple system atrophy, the low-frequency energy of systolic blood pressure decreased significantly. The changes observed in the low-frequency band and the high-frequency band of heart rate (reflecting parasympathetic drive to the heart) were not different among the three groups. These data show the lack of impairment in autonomic nervous system activity in patients with progressive supranuclear palsy.

Aged↗
PubMed1999

Lack of pharmacokinetic interaction between ropinirole and theophylline in patients with Parkinson's disease.

OBJECTIVE: Ropinirole and theophylline have the potential to interact, because they use the same hepatic cytochrome P450 (CYP1A2) as their major metabolic pathway. The present study investigated the effect of steady-state oral theophylline on the pharmacokinetics of ropinirole at steady state and the effect of steady-state ropinirole on the pharmacokinetics of a single intravenous (i.v.) dose of theophylline, both in patients with idiopathic Parkinson's disease (PD). METHODS: Pharmacokinetic parameters (AUC and Cmax) for i.v. theophylline were compared before and after a 4-week period of oral treatment with ropinirole (2 mg t.i.d.) in 12 patients with PD. Patients were then maintained at this dose of ropinirole, and oral theophylline was co-administered at doses of up to 300 mg b.i.d. The parameters AUC, Cmax and tmax for ropinirole were compared before, during and after oral theophylline co-treatment. RESULTS: Co-administration of ropinirole did not significantly change the pharmacokinetics of i.v. theophylline (mean AUC with and without ropinirole: 68.6 micog x h(-1) x ml(-1) and 70.0 microg x h(-1) x ml(-1), respectively: mean Cmax with and without ropinirole: 11.07 microg x ml(-1) and 11.83 microg x ml(-1), respectively). Similarly, there were no significant changes in ropinirole pharmacokinetics when the drug was co-administered with oral theophylline (mean AUC for ropinirole with and without theophylline: 21.91 ng x h(-1) x ml(-1) and 22.09 ng x h(-1) x ml(-1), respectively; mean Cmax for ropinirole with and without theophylline: 5.65 ng x ml(-1) and 5.54 ng x ml(-1), respectively; median tmax for ropinirole with and without theophylline: 2.0 h and 1.5 h, respectively). CONCLUSION: These results suggest a lack of significant pharmacokinetic interaction between the two drugs at current therapeutic doses.

Administration, Oral↗
PubMed1999

Spontaneously hypertensive rats cholinergic hyper-responsiveness: central and peripheral pharmacological mechanisms.

1. The mechanisms and the subtypes of muscarinic receptors implicated in the cardiovascular effects of physostigmine were investigated in conscious normotensive and spontaneously hypertensive rats. 2. Intravenous (i.v.) physostigmine (50 microg kg-1) induced in both strains a long pressor response, accompanied by a bradycardia. This pressor response was larger in spontaneously hypertensive (+41+/-6 mmHg) than in Wistar-Kyoto (+25+/-2 mmHg) rats (P<0.05). 3. Pretreatment with atropine sulphate (0.4 mg kg-1 i.v.), completely abolished the physostigmine-induced pressor response in both normotensive and hypertensive rats. In both strains, the physostigmine pressor response was significantly reduced by the systemic administration of either an alpha1-adrenoceptor antagonist (prazosin, 1 mg kg-1) or a V1A-vasopressin receptor antagonist (AVPX, 20 microg kg-1). This physostigmine pressor effect was completely abolished in both strains when both antagonists were administered concomitantly. 4. In WKY rats, the pressor response to physostigmine (50 microg kg-1 i.v.) was inhibited in a dose-dependent manner by i. c.v. administration of atropine (ID50=3.70 nmoles), the M1 receptor antagonist pirenzepine (ID50=10.71 nmoles), the M2 receptor antagonist methoctramine (ID50=4.31 nmoles), the M3 receptor antagonist p-F-HHSiD (ID50=60.52 nmoles) and the M4 receptor antagonist tropicamide (ID50=214.20 nmoles). In the hypertensive strain, the ID50 were found to be significantly higher for atropine (7.34 nmoles), pirenzepine (21.60 nmoles) and p-F-HHSiD (139.50 nmoles) (P<0.05). 5. The present results indicate that physostigmine acts in normotensive and spontaneously hypertensive rats, through stimulation of both central M2 and M1 cholinoceptors to induce a rise in blood pressure mediated by an increase in plasma vasopressin and sympathetic outflow. Moreover, our results suggest that some modifications of the M1 receptor subtypes in terms of expression or affinity could be responsible for the hyper-responsiveness of the hypertensive strain to cholinomimetic agents.

Animals↗
PubMed1999

A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease.

Autosomal recessive juvenile parkinsonism (AR-JP, PARK2; OMIM 602544), one of the monogenic forms of Parkinson's disease (PD), was initially described in Japan. It is characterized by early onset (before age 40), marked response to levodopa treatment and levodopa-induced dyskinesias. The gene responsible for AR-JP was recently identified and designated parkin. We have analysed the 12 coding exons of the parkin gene in 35 mostly European families with early onset autosomal recessive parkinsonism. In one family, a homozygous deletion of exon 4 could be demonstrated. By direct sequencing of the exons in the index patients of the remaining 34 families, eight previously undescribed point mutations (homozygous or heterozygous) were detected in eight families that included 20 patients. The mutations segregated with the disease in the families and were not detected on 110-166 control chromosomes. Four mutations caused truncation of the parkin protein. Three were frameshifts (202-203delAG, 255delA and 321-322insGT) and one a nonsense mutation (Trp453Stop). The other four were missense mutations (Lys161Asn, Arg256Cys, Arg275Trp and Thr415Asn) that probably affect amino acids that are important for the function of the parkin protein, since they result in the same phenotype as truncating mutations or homozygous exon deletions. Mean age at onset was 38 +/- 12 years, but onset up to age 58 was observed. Mutations in the parkin gene are therefore not invariably associated with early onset parkinsonism. In many patients, the phenotype is indistinguishable from that of idiopathic PD. This study has shown that a wide variety of different mutations in the parkin gene are a common cause of autosomal recessive parkinsonism in Europe and that different types of point mutations seem to be more frequently responsible for the disease phenotype than are deletions.

Binding Sites↗
PubMed1999

[Reduction of the pressor effect of fluoxetine after V1A-vasopressin receptor blockade in the conscious rats].

Pharmacovigilance data have reported some cases of arterial hypertension in patients treated with serotonin reuptake inhibitors. This side effect is now called serotonin syndrome. Moreover, some authors have shown that these drugs could reduce, at least in part, the fall in blood pressure (BP) observed in experimental models or in human forms of orthostatic hypotension, suggesting a modulation of the autonomic nervous system by these drugs. These data led us to study in freely moving Wistar rats the mechanisms involved and the putative involvement of autonomic nervous system. Intracerebroventricular (i.c.v.) administration of fluoxetine (5-50 micrograms) induced an increase in BP similar to which was obtained following central administration of serotonin (5-HT) (0.5-5 micrograms). After 5-HT, the pressor effect was immediate (1 min following injection) and involved the baroreflex pathway (bradycardia). The fluoxetine-induced pressor response reached its maximal 1 hour after injection without any significant change in heart rate (HR). At the dose of 10 micrograms i.c.v., fluoxetine significantly increased mean BP by 16 +/- 4 mmHg. This pressor response was partially but significantly reduced by a pretreatment by the alpha 1-adrenoreceptor antagonist, prazosin (500 micrograms.kg-1 i.v.) (+7 +/- 4 mmHg, p < 0.05) or by a V1A-vasopressin receptor antagonist (20 micrograms.kg-1 i.v.) (+5 +/- 3 mmHg, p < 0.05). However, pretreatment by the beta-adrenoreceptor antagonist, propranolol (1 mg.kg-1 i.v.) and the antagonist 5-HT2, ketanserine (5 mg.kg-1 i.v.) did not modify the fluoxetine-induced pressor response. In freely moving rats receiving fluoxetine (10 micrograms i.c.v.), vasopressin plasma levels were significantly higher (+39 +/- 5 pg.mL-1) than in rats receiving saline (100 microL i.c.v.) (+14 +/- 4 pg.mL-1), thus confirming the involvement of vasopressinergic mechanisms in the fluoxetine-induced pressor response. These data suggest that in freely moving Wistar rats, central acute administration of fluoxetine induces a pressor response mediated by both an increase in sympathetic tone and a vasopressin release. This observation could suggest the putative use of alpha 1-adrenoreceptors antagonists and/or V1A-vasopressin receptor antagonists in the treatment of the serotonin syndrome.

Analysis of Variance↗