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Biomedical subjects

O Rascol

Publications and source records attributed to O Rascol.

At least 91 records · Page 5Linked to original sources
PubMed1997

Prevalence of orthostatic hypotension in Parkinson's disease.

OBJECTIVES: To investigate the prevalence of orthostatic hypotension and the nature of the postural events related to a fall in blood pressure in patients with Parkinson's disease. METHODS: Blood pressure was measured first in a supine position after a rest of at least 15 minutes and every minute during 10 minutes of an active standing up procedure. Orthostatic hypotension was considered as present when a fall of at least 20 mm Hg of systolic blood pressure was recorded. Postural events which occurred during the standing test were identified from a questionnaire and self reporting. Statistical analysis was performed to determine the relation between orthostatic hypotension and disease characteristics (duration, severity) and the use of antiparkinsonian drugs. Ninety one consecutive patients with Parkinson's disease (48 women, 43 men, mean age 66 (SD 9) years) participated to the study. RESULTS: A fall of at least 20 mm Hg of systolic blood pressure was found in 58.2% of the patients. Orthostatic hypotension was asymptomatic in 38.5% and associated with postural events in 19.8% of the patients. Symptomatic (but not asymptomatic) orthostatic hypotension was related to duration and severity of the disease and with the use of higher daily levodopa and bromocriptine doses. The analysis of the relation between the postural symptoms (and the need for standing test abortion) with the fall in systolic blood pressure allowed the identification of six clinical criteria specific of orthostatic hypotension. A direct relation between the postural changes in systolic blood pressure and the number of clinical events in this clinical scale was found. CONCLUSION: The frequency of orthostatic hypotension in Parkinson's disease is high and it is possible to establish a clinical rating scale which could be used to assess the effects of drugs employed in the management of orthostatic hypotension.

Aged↗
PubMed1996

The discovery of vasomotor nerves.

The relative contribution of Claude Bernard and Charles Edouard Brown-Séquard to the discovery of vasomotor nerves is described and discussed. The controversy surrounding these two founding fathers of autonomic physiology and pharmacology is also summarized. In 1851, Bernard showed that section of the cervical sympathetic nerve unexpectedly elicited a marked and rapid increase in skin temperature. In 1852, Brown-Séquard extended these observations and established the relationship between blood vessels and the sympathetic nervous system. Thus, Brown-Séquard was the first to demonstrate the existence of sympathetic vasoconstrictor fibres. In contrast, Bernard discovered vasodilator nerves and is the founder of the modern concept of vasomotricity.

Anatomy↗
PubMed1996

Ropinirole in the treatment of levodopa-induced motor fluctuations in patients with Parkinson's disease.

Forty-six patients with Parkinson's disease experiencing motor fluctuations and not optimally controlled on levodopa received as adjunct therapy a new nonergoline dopamine agonist, ropinirole, in a 3-month randomized placebo-controlled trial. Ropinirole significantly reduced the duration of off periods as assessed by self-scoring diary cards. There were more nonserious dopaminergic adverse events in the ropinirole group. More patients withdrew because of adverse events or insufficient therapeutic effect in the placebo group. Ropinirole has beneficial adjuvant effects in parkinsonian patients with moderate motor disability and motor fluctuations.

Adult↗
PubMed1996

A study of dopaminergic sensitivity in Parkinson's disease: comparison in "de novo" and levodopa-treated patients.

The present study investigates dopaminergic sensitivity in Parkinson's disease (PD) through the measurement of neuroendocrine (growth hormone: GH, prolactin: PRL) and cardiovascular (blood pressure: BP, heart rate: HR) responses to low doses of apomorphine (5 micrograms/kg s.c.) in three groups of subjects: 13 normal volunteers (controls), 19 "de novo" never-treated PD patients, and 14 levodopa-treated PD patients. Apomorphine did not change BP and HR but significantly decreased PRL plasma levels in controls as well as in the two groups of PD patients. GH plasma levels significantly increased after apomorphine. There was no significant difference in the changes in neuroendocrine (GH, PRL) parameters in the two groups of PD patients in comparison with controls. However, "de novo" patients exhibited a significantly higher number of apomorphine-induced orthostatic symptoms (7 of 19) than did controls (0 of 13) or treated PD patients (2 of 14). These results show that hypothalamic dopaminergic sensitivity (studied through GH and PRL responses to apomorphine) is normal in PD. In contrast, because apomorphine-induced orthostatic hypotension is mainly due to the stimulation of peripheral dopaminergic receptors, our study suggests a peripheral dopaminergic hypersensitivity in some "de novo" never treated (but not in treated) PD patients.

Adult↗
PubMed1996

A study of tolerance to apomorphine.

1. The present study was designed to investigate tolerance to several pharmacological effects of apomorphine. 2. Changes in blood pressure, heart rate, plasma noradrenaline levels, rectal temperature, respiratory rate and retching plus vomiting were compared after administration of apomorphine (200 micrograms kg-1, i.v. as a bolus) or saline at different time intervals (30, 120 and 720 min) in four groups of chloralose-anaesthetized dogs. 3. The first administration of apomorphine induced a significant decrease in blood pressure and rectal temperature, a marked rise in heart rate with no change in noradrenaline plasma levels or respiratory rate. Emesis occurred in 71% of the animals. 4. A second administration of apomorphine 30 min later failed to modify blood pressure or heart rate. In contrast, the magnitude of apomorphine-induced changes in blood pressure and heart rate was similar to that observed after the first administration when apomorphine was given 120 or 720 min later. 5. The apomorphine-induced decrease in rectal temperature evoked by a second dose of apomorphine was less marked when given 30 and 120 min after the first dose and unchanged when given 720 min later. 6. The number of animals exhibiting retching and vomiting was lower when apomorphine was reinjected after 30 min than when the time between two successive injections of apomorphine was 120 or 720 min. 7. These results show that tolerance to apomorphine involves its cardiovascular, hypothermic and emetic effects. The time course of tolerance to repeated injections of apomorphine is longer for its hypothermic than for its hypotensive or emetic effects. This suggests a tissue-specific regulation of D2 dopamine receptors to repeated injections of apomorphine.

Animals↗
PubMed1996

New directions in the drug treatment of Parkinson's disease.

Parkinson's disease, a clinical syndrome with 4 cardinal features (bradykinesia, resting tremor, increased muscular rigidity and impaired postural balance), is mainly caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. Although levodopa remains the 'gold standard' in the treatment of the disease, several emerging strategies are currently being developed. The first concerns new symptomatic drugs that either potentiate the effects of levodopa (e.g. slow-release preparations of levodopa, catechol-O-methyltransferase inhibitors and new dopamine agonists) or target clinical symptoms resistant to dopaminergic drugs (e.g. glutamate antagonists). The second strategy is to find drugs that are able to prevent or delay the neuronal death observed in Parkinson's disease. Several neuroprotective drugs are now in development in experimental research, but clinical trials in this area are still lacking. The development of these new drugs also depends on the validation of new clinical methodologies.

Antiparkinson Agents↗
PubMed1995

Abnormal vestibuloocular reflex cancellation in multiple system atrophy and progressive supranuclear palsy but not in Parkinson's disease.

We have measured the gain of the vestibuloocular reflex (VOR) in darkness and its cancellation by fixation in 37 patients with Parkinson's disease (PD), 26 patients with multiple system atrophy (MSA), 11 patients with progressive supranuclear palsy (PSP), and 19 normal volunteers. The capacity to cancel the VOR by fixation (VOR cancellation) was significantly reduced in the MSA and PSP patients compared with the PD and normal subjects (p < 10(-4)). A VOR cancellation < 90% (i.e., the mean VOR cancellation of the normals--2 SD) was present in four PD patients, 23 MSA patients, and 11 PSP patients. This criteria distinguished PD and MSA with a 89% sensitivity and a 89% specificity. Our results demonstrate that the VOR cancellation is impaired in most patients with MSA and PSP but not with PD. In MSA patients, the abnormal VOR cancellation is probably not related to the nigrostriatal dopaminergic deficit and more likely reflects a cerebellar dysfunction. Impaired VOR cancellation is a clinical criteria to differentiate MSA and PSP from PD.

Age Factors↗
PubMed1995

Central cardiovascular effects of acetylcholine in the conscious dog.

1. The effects of central cholinomimetic drugs on cardiovascular and vasoactive hormonal responses (blood pressure, heart rate, catecholamines, vasopressin, atrial natriuretic factor, neuropeptide Y plasma levels and plasma renin activity) were investigated in conscious Beagle dogs. For this purpose a catheter was chronically implanted into each dog's cisterna magna to allow repeated central injections in the awake animals. 2. Intracisternal acetylcholine (20 micrograms kg-1) significantly increased systolic and diastolic blood pressure. These changes were accompanied by an initial short term tachycardia followed by a long lasting bradycardia. Intracisternal acetylcholine also increased noradrenaline, adrenaline and vasopressin plasma levels, decreased plasma renin activity but did not modify plasma levels of neuropeptide Y and atrial natriuretic factor. 3. The effects of acetylcholine were completely abolished by pretreatment with intracisternal injection of the muscarinic antagonist, atropine (5 micrograms kg-1) but not by the intracisternal injection of the nicotinic antagonist, mecamylamine (25 micrograms kg-1). 4. The present results demonstrate that there are qualitative and quantitative differences between the central cardiovascular effects of acetylcholine in conscious dogs compared to what we previously reported, using a comparable protocol, in anaesthetized dogs. Under both conditions, we observed a central cholinergically mediated increase in blood pressure secondary to an increase in sympathetic tone and vasopressin release but these responses were shorter (less than 10 min) in the conscious dogs than in anaesthetized dogs (more than 10 min). Moreover, we detected in the response to the central cholinergic stimulation in the conscious dogs a significant increase in plasma adrenaline levels and biphasic changes in heart rate which were not described previously in the anaesthetized dog.

Acetylcholine↗
PubMed1995

Treatment of hemifacial spasm with botulinum toxin. Value of preinjection electromyography abnormalities for predicting postinjection lower facial paresis.

Thirty-two patients with hemifacial spasm were treated with 61 botulinum toxin (BT) injections. Some patients had post-BT lower facial paresis (LFP+group) while others did not suffer this side effect (LFP-group). Abnormal electromyography (EMG) recordings were more frequent in the LFP+ group (6/11) than in the LFP- group (3/21; p < 0.05). This result suggests that an EMG performed before any BT injection could detect the patients with a higher risk for this side effect. The first dose of BT might be lowered in such cases.

Aged↗
PubMed1995

Effects of acute levodopa administration on blood pressure and heart variability in never treated parkinsonians.

The effects of levodopa on autonomic nervous system (ANS) were investigated through the measurement of blood pressure (BP) and heart rate (HR) variability in 15 de novo parkinsonian who never received dopaminergic drugs. BP and HR were obtained using digital photoplethysmography in supine and standing positions. Measurements were achieved 90 min after administration, in a double blind cross-over way, of placebo or levodopa (200 mg)+benserazide (50 mg). Spectral analysis was performed using fast Fourier transformation (FFT) on 512 consecutive SBP and HR values. Spectral modulus was integrated for calculation of total spectra and of low frequency (LF: 66-129 mHz) or high frequency band (HF: respiratory frequency +/- 50 mHz). After placebo, orthostatism was followed by a significant increase in BP and HR whereas relative variabilities in LF and HF remained unchanged. After levodopa, BP was significantly lower in supine position without changes in HR and LF. During orthostatism, changes observed in BP and in FFT were similar to those observed during placebo period. These data indicate that levodopa reduces supine and standing BP but does not impair orthostatic adaptation. This effect is not due to modification of BP or HR variability and appears to independent of any direct effect on ANS.

Blood Pressure↗
PubMed1995

Antivertigo medications and drug-induced vertigo. A pharmacological review.

The approach to drug treatment of vertigo is almost exclusively symptomatic. There are 3 major goals for drug treatment of vertigo. The first one is to eliminate the hallucination of motion. Drugs with vestibular 'suppressant' properties are used for this purpose. The major vestibular suppressants are anticholinergic and antihistamine drugs. The second goal is to reduce the accompanying neurovegetative and psychoaffective signs (nausea, vomiting, anxiety). Antidopaminergics are used for this purpose. The third goal is to enhance the process of 'vestibular compensation' to allow the brain to find a new sensory equilibrium in spite of the vestibular lesion. Until now, the pharmacological manipulation of vestibular compensation has been assessed in animals but not in humans with vestibular lesions. Vestibular suppressant drugs delay rather than enhance compensation. A variety of other drugs is also used in the treatment of vertigo, including benzodiazepines, histaminergic agents, sympathomimetics and calcium antagonists. Their mechanism of action is poorly understood. The data base derived from clinical trials evaluating antivertigo medications is often questionable because of methodological limitations. This explains why habits of prescription are mainly empirical, and why striking differences can be noticed from one country to another. We can hope that new treatments may emerge from the present interest in receptor subclasses and neuromodulators of the vestibular system, and we must be ready to evaluate these potential new pharmacological agents with reliable clinical methods in humans.

Animals↗
PubMed1995

Sublingual apomorphine: a new pharmacological approach in Parkinson's disease?

Apomorphine, a potent dopamine agonist with mixed D1 and D2 properties, has long been recognized to have antiparkinsonian effect. Its oral administration is limited by both its hepatic first pass metabolism and adverse side effects (nausea, vomiting, azotemia). It is now widely used by subcutaneous route for the treatment of severe "off" periods seen with levodopa treatment. However, the use of penjects can be difficult in some patients with severe tremor or akineto-rigid symptoms during "off" periods. Our group has recently investigated the effect of sublingual administration of apomorphine in patients suffering from Parkinson's disease. Sublingual apomorphine was shown to reduce extrapyramidal symptoms. The main characteristics of the pharmacodynamic effects of sublingual apomorphine in parkinsonians and the relationship between pharmacodynamic and pharmacokinetic effects are discussed. Sublingual apomorphine has the advantage of being easier to administer than subcutaneous injection. For the moment, the long-term use of sublingual apomorphine is limited by two major problems: first, time for dissolution and switch "on" (which is longer than after subcutaneous route) and secondly, the occurrence of local side effects (stomatitis). Further clinical studies using either more efficient (tablets with faster dissolution) and better tolerated sublingual formulations or other dopamine agonists should be carried on before recommending this approach in the treatment of Parkinson's disease.

Administration, Sublingual↗