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Biomedical subjects

J Paquereau

Publications and source records attributed to J Paquereau.

At least 19 recordsLinked to original sources

Pharmacokinetic-pharmacodynamic modelling of the electroencephalogram effect of imipenem in rats with experimental hypovolaemia or endotoxaemia.

OBJECTIVES: The epileptogenic activity of imipenem in rats with experimentally induced hypovolaemia or endotoxaemia was investigated by pharmacokinetic-pharmacodynamic modelling of the electroencephalogram effect. METHODS: Hypovolaemia was induced by removal of 30% of the blood volume and endotoxaemia by intravenous lipopolysaccharide injection. RESULTS: Imipenem clearance and volume of distribution values of 16.4+/-1.1 mL/min per kg and 357+/-49 mL/kg (mean+/-S.E.M.) in healthy rats (n=5), were significantly reduced in hypovolaemic (n=6) and endotoxaemic (n=6) animals. A dose reduction from 250 mg/kg to 120 mg/kg was necessary in endotoxaemic rats. The pharmacokinetic-pharmacodynamic model with an effect compartment previously developed in healthy rats described the data adequately and pharmacodynamic parameters in hypovolaemic and endotoxaemic rats were not significantly different from corresponding values estimated in the control group. CONCLUSION: Hypovolaemia and endotoxaemia only had an effect on imipenem pharmacokinetics.

Algorithms↗

Do robots need to sleep?

The present paper exposes algorithmic results providing a vision about sleep functions which complements biological theory and experiments. Derived from the algorithmic theory of information, the theory of adaptation aims at quantifying how an inherited or acquired piece of knowledge helps individuals to survive. It gives a scale of complexity for survival problems and proves that some of them can only be solved by a dynamical management of memory associating continuous learning and forgetting methods. In this paper we explain how a virtual robot "Picota" has been designed to simulate the behavior of a living hen. In order to survive in its synthetical environment, our robot must recognize good seeds from bad ones, and should take rest during night periods. Within this frame, and facing the rapid evolution of to-be-recognized forms, the best way to equilibrate the energetic needs of the robot and ensure survival is to use the nightly rest to reorganize the pieces of data acquired during the daily learning, and to trash the less useful ones. Thanks to this time sharing, the same circuits can be used for both daily learning and nightly forgetting and thus costs are lower; however, this also forces the system to "paralyse" the virtual robot, and therefore the night algorithm is reminiscent of paradoxical (REM) sleep. The algorithm of the robot takes advantage of the alternation between wakefulness or activity and the rest period. This diagram quite accurately recalls the REM period. In the future, the convergence between the neurophysiology of sleep and the theory of complexity may give us a new line of research in order to elucidate sleep functions.

Algorithms↗

[Sleep apnea syndrome in the elderly].

INTRODUCTION: Sleep apnoea/hypopnoea syndrome (SAHS) is distinct in the elderly as age-related co-morbidity may be aggravated by sleep-related breathing disorders or may mask typical clinical symptoms. STATE OF ART: The SAHS prevalence in the elderly varies from one study to another, with an average rate of 25% that might increase according to the importance of associated pathologies. Clinical symptoms tend to be the neurological manifestations of excessive daytime sleepiness and cognitive deterioration. PERSPECTIVES: Treatment of SAHS should include weight reduction strategies if obesity is present. There is no role for surgery in this age group. On the other hand, adjustable oral appliances can be used depending on the severity of the SAHS, but nasal continuous positive airway pressure (CPAP) remains the most effective therapy available. Acceptance of and compliance with CPAP treatment is as good in this age group as in younger patients, with remarkable effectiveness in terms of improvement in daytime sleepiness and cognitive function. However, the effectiveness of treatment for SAHS is related to the level of symptoms present and this should be taken into account when making a therapeutic decision. CONCLUSIONS: These results fully justify treatment of SAHS in the elderly, but the decision to treat should be governed by the level of clinical symptoms from SAHS.

Aged↗

[Sleep apnea syndrome in the elderly].

INTRODUCTION: Sleep apnoea/hypopnoea syndrome (SAHS) is distinct in the elderly as age-related co-morbidity may be aggravated by sleep-related breathing disorders or may mask typical clinical symptoms. STATE OF ART: The SAHS prevalence in the elderly varies from one study to another, with an average rate of 25% that might increase according to the importance of associated pathologies. Clinical symptoms tend to be the neurological manifestations of excessive daytime sleepiness and cognitive deterioration. PERSPECTIVES: Treatment of SAHS should include weight reduction strategies if obesity is present. There is no role for surgery in this age group. On the other hand, adjustable oral appliances can be used depending on the severity of the SAHS, but nasal continuous positive airway pressure (CPAP) remains the most effective therapy available. Acceptance of and compliance with CPAP treatment is as good in this age group as in younger patients, with remarkable effectiveness in terms of improvement in daytime sleepiness and cognitive function. However, the effectiveness of treatment for SAHS is related to the level of symptoms present and this should be taken into account when making a therapeutic decision. CONCLUSIONS: These results fully justify treatment of SAHS in the elderly, but the decision to treat should be governed by the level of clinical symptoms from SAHS.

Aged↗

[Respiratory disorders during sleep in the pregnant woman].

Sleep disordered breathing can occur during pregnancy due to the development of hormonal changes and respiratory function abnormalities that perturb patency of the upper airways. Habitual snoring has been described in 25 p. 100 of the women during the third trimester of pregnancy. The incidence of sleep apnea hypopnea syndrome is unknown due to the lack of longitudinal epidemiological data, and results of the main studies are in favor of upper airway resistance syndrome. However, these sleep-related breathing disorders are more frequently associated with maternal and fetal complications such as maternal hypertension, pre eclampsia and intrauterine growth restriction. This article points out the importance of such associations because of the efficacy of continuous positive airway pressure on the regression of these nocturnal respiratory and vascular complications.

Airway Resistance↗

Relationship between sleep apnoea syndrome, snoring and headaches.

There is still a controversy regarding the relationship between sleep apnoea syndrome and headaches, especially morning headaches. Our objectives were: (i) to compare the prevalence and the clinical data of headaches in sleep apnoea syndrome (SAS) and control (snorers) groups defined by polysomnographic recording; (ii) to analyse the clinical improvement of headaches with appropriate treatment; and (iii) to correlate headaches with mood disorders, and nocturnal respiratory and architectural sleep parameters in order to understand the underlying pathophysiological mechanisms. This is a prospective study of 324 consecutive patients referred to our sleep centre for snoring. Of these, 312 patients who underwent sleep polysomnography were finally included. Patients and controls were interviewed about their medical past, headache history and clinical characteristics, their daytime sleepiness (Epworth's sleepiness scale) and their mood disorders (Zerssen's scale). Follow-up of patients with headaches (SAS and control groups), treated or not, was also assessed. According to our definition of SAS, patients were dissociated in SAS (n=164) and snorers (n=148). Fifty-three SAS patients had headaches, of whom 58.5% (n=30) suffered from morning headaches. However, there was no statistical difference between the two groups concerning the prevalence and the clinical characteristics of headaches. In addition, headaches and morning headaches were not correlated with nocturnal respiratory and architectural sleep parameters, nor with excessive daytime sleepiness, but were strongly correlated with mood disorders. In 36 SAS patients, headaches improved under treatment, but this was not statistically different from what was found among untreated snorers. Headaches and morning headaches are common in patients with SAS but may be considered as a non-specific symptom. The underlying mechanisms are not fully elucidated but depression could play an important role. Despite this absence of specificity, the treatment of SAS, especially nasal continuous positive airway pressure, leads to an improvement in headaches in several cases.

Antidepressive Agents↗

[The sleep apnea syndrome: diagnosis and management in general practice. A descriptive survey of 579 French general practitioners].

General practitioners (GP's) should be the first to recognise the sleep apnoea/hypopnoea syndrome (SAHS) and could play a major role in the follow up of patients treated with continuous positive airways pressure (CPAP) at home. We have carried out a prospective study in order to evaluate the knowledge and diagnostic and therapeutic practice of GP's in relation to SAHS. 579 GP's agreed to participate in the study by means of a telephone questionnaire. Although daytime somnolence and the presence of apnoeas and snoring were the most frequently quoted clinical symptoms suggesting the diagnosis of SAHS, a combination of these symptoms was quoted in only one third of cases. On the other hand the complications of SAHS were not well known by GP's as only 25% of them mentioned the possibility of cardiovascular complications; cerebrovascular accidents and arterial hypertension being quoted by only 15% and 8.8% respectively. With regard to the follow up of patients treated with CPAP more than 50% of GP's did not know the minimum duration of ventilation required and 60% did not understand the method of function. These results, which emphasise the underestimation of SAHS and its complications, confirm the need to develop an educational strategy specifically for GP's in an attempt to improve the diagnosis of this disorder and to allow them to take part in the management and monitoring of treatment with CPAP.

Cardiovascular Diseases↗

Pharmacokinetic-pharmacodynamic modeling of electroencephalogram effect of imipenem in rats with acute renal failure.

The epileptogenic activity of imipenem was investigated in rats with experimental renal failure induced by uranyl nitrate injection by using electroencephalogram (EEG) recording and a pharmacokinetic-pharmacodynamic model including an effect compartment. Results previously obtained with healthy rats were used to estimate the dose of imipenem required to induce an observable but nonlethal EEG effect on the assumption that only the pharmacokinetic parameters of the model would be affected by renal failure. Good agreement was observed between the predicted and observed effects.

Acute Kidney Injury↗

Pharmacokinetic-pharmacodynamic modeling of the electroencephalogram effect of imipenem in healthy rats.

A pharmacokinetic-pharmacodynamic (PK-PD) modeling approach was developed to investigate the epileptogenic activity of imipenem in rats. Initially, animals received an intravenous infusion of imipenem at a rate of 2.65 mg min(-1) for 30 min. Blood samples were collected for drug assay, and an electroencephalogram (EEG) was recorded during infusion and postinfusion. A dramatic delay was observed between concentrations of imipenem in serum and the EEG effect; this effect was accompanied by tremors and partial seizures. Indirect-effect models failed to describe these data, which were successfully fitted using an effect compartment model. The relationship between effect and concentration at the effect site was best described by a spline function. The elimination rate constant from the effect compartment was severalfold lower than that from the central compartment. The robustness of the model was then confirmed after administering the imipenem dose over 60 and 90 min. In conclusion, the successful PK-PD modeling of the imipenem EEG effect in rats constitutes a major improvement for better prediction of the epileptogenic risk associated with this antibiotic.

Animals↗

[Titration of an effective positive pressure level in the treatment of obstructive sleep apnea syndromes using continuous positive pressure ventilation].

The efficacy of continuous airway positive pressure ventilation with a nasal mask mainly depends on the appropriateness of the effective positive pressure level. Conventionally, this level is determined from polysomnographic recordings using progressively increasing pressure levels to determine the point where episodes of apnea, hypopnea and snoring regress in all sleep phases and in all body positions. Since the first description of this method, many other titration methods have been proposed. Some use sophisticated signals such as the analysis of respiratory exertion level or limitation of inspiratory flow to provide a more precise titration which is particularly useful in cases where the classical titration method is insufficiently effective. Inversely, simplified methods have been examined from an economic point of view. These methods do not require the presence of a technician in a specialized laboratory where the waiting list for diagnostic tests is often long. Recordings during naps or short nights have been proposed for the more severe cases. Likewise titrations during simple polygraphy recordings or with an autoCPAP device have been shown to be effective in one-night laboratory recordings. Much work remains to be done to determine the effectiveness of these methods when used in the patient's home as well the long-term effects.

Humans↗

[Titration of the level of effective positive pressure in the treatment of obstructive sleep apnea syndromes with continuous positive pressure].

The efficacy of continuous airway positive pressure ventilation with a nasal mask mainly depends on the appropriateness of the effective positive pressure level. Conventionally, this level is determined from polysomnographic recordings using progressively increasing pressure levels to determine, the point where episodes of apnea, hypopnea and snoring regress in all sleep phases and in all body positions. Since the first description of this method, many other titration methods have been proposed. Some use sophisticated signals such as the analysis of respiratory exertion level or limitation of inspiratory flow to provide a more precise titration which is particularly useful in cases where the classical titration method is insufficiently effective. Inversely, simplified methods have been examined from an economic point of view. These methods do not require the presence of a technician in a specialized laboratory where the waiting list for diagnostic tests is often long. Recordings during naps or short nights have been proposed for the more severe cases. Likewise titrations during simple polygraphy recordings or with an autoCPAP device have been shown to be effective in one-night laboratory recordings. Much work remains to be done to determine the effectiveness of these methods when used in the patient's home as well the long-term effects.

Home Care Services↗

Footshock stress but not contextual fear conditioning induces long-term enhancement of auditory-evoked potentials in the basolateral amygdala of the freely behaving rat.

In this study, rats were bilaterally implanted with electrodes in the amygdala for chronic recording. Auditory click stimulation evoked in the basolateral nucleus a field potential characterized by three positive components: P1, P2 and P3 (peak latencies around: 10, 20 and 30 ms, respectively) which were each followed by three negative components: N1, N2 and N3 (peak latencies around: 13, 30 and 50 ms, respectively). Animals were divided into three groups (context-same, context-different and control). Following footshock administration, animals were either re-exposed to the same conditioning chamber (context-same group) or placed in a different context (context-different group) for electrophysiological and behavioural (evaluation of freezing response) recordings. The two early positive-negative complexes (P1-N1 and P2-N2) increased in amplitude from 2 min to 24 h following footshock in both context-same and context-different groups. No significant difference was observed between these two groups. The demonstration of significantly larger freezing responses in context-same subjects on exposure to the aversive conditioned environment indicated that this similarity of effects was not due to lack of conditioning of context under the experimental conditions chosen. We conclude that footshock stress produces general long-lasting changes in amygdala auditory field potentials that are not significantly affected by contextual fear conditioning.

Acoustic Stimulation↗

Influence of correction of flow limitation on continuous positive airway pressure efficiency in sleep apnoea/hypopnoea syndrome.

We evaluated the efficiency of two different treatment procedures with continuous positive airway pressure (CPAP) on sleep, nocturnal breathing characteristics and daytime vigilance in 18 newly diagnosed patients with untreated sleep apnoea/hypopnoea syndrome (SAHS) randomly allocated to two different groups. In group I, the positive pressure (PP) level was set to suppress flow limitation (PFL), while in group II the PP was set at a level that eliminated only apnoea/hypopnoea and snoring (PAHS). At the end of a 3 week period of home CPAP therapy, a follow-up sleep study, vigilance and cognitive tests were made. Overall, PFL was significantly higher than PAHS values (PFL: 10.42.6 cmH2O; PAHS: 8.9+/-2.6 cmH2O; p<0.01, mean+/-SD). We found no difference in sleep quality, nocturnal saturation and apnoea/hypopnoea index, or in daytime vigilance tests between the two groups at the end of the treatment period. However, there was a significantly greater scattering in the changes of sleep latency in group II than in group I. This was associated with a significant difference in the daily duration of nasal CPAP use between the two groups (group I: 7.29+/-0.95 h x day(-1); group II: 6.01+/-0.94 h x day(-1); p=0.01) and with a positive correlation between final maintenance of wakefulness test values and the duration of CPAP use (p<0.05; r=0.55). These results tend to show that correcting flow limitation is associated with a higher observance and a more important efficiency in normalizing daytime vigilance than with conventional nasal continuous positive airway pressure.

Aged↗

Long-term evolution of daytime somnolence in patients with sleep apnea/hypopnea syndrome treated by continuous positive airway pressure.

We demonstrated in a previous study that excessive daytime sleepiness (EDS) in patients who have sleep apnea/hypopnea syndrome (SAHS) and are undergoing continuous positive airway pressure (CPAP) treatment improved differently in two groups of patients: in group I, multiple sleep latency tests (MSLT) were normalized after 50 days of treatment (individual value > 10 minutes), whereas they remained low (individual value < 10 minutes) in group II, with a significant difference between groups. To evaluate the long-term evolution of daytime somnolence under nasal CPAP treatment, five patients from group I and seven patients from group II underwent a new polysomnography and MSLT 4 years after the previous study. Clinical, polysomnographic and MSLT results obtained at baseline before treatment (T1), after the initial 50-day period of CPAP treatment (T2), and after 4 years (T3) were compared. The significant difference in mean MSLT value between the two groups previously observed at T1 and T2 disappeared at T3 (group I: 12.4+/-5.9 minutes; group II: 9.7+/-5.9 minutes). We found that this long-term improvement in excessive daytime somnolence was independent of the initial MSLT value, the severity of SAHS, and the initial MSLT changes under nasal CPAP. Long-term MSLT evolution was significantly correlated to CPAP compliance. These results demonstrate that even in the absence of a significant increase in MSLT at the beginning of CPAP treatment, further improvement is still possible several years later, which may encourage the regular, long-term use of nasal CPAP by patients.

Aged↗

Habitual snoring as a risk factor for brain infarction.

The association of habitual snoring with cerebral ischaemia was studied, in a case control-study, in 133 patients aged 45-75 years (103 men and 30 women) and 133 controls matched for sex and age. Ischaemic stroke was confirmed by brain computed tomography or magnetic resonance imaging. History of risk factors, especially of snoring and sleeping habits was recorded with structured questionnaire during interview. Prevalence of habitual snoring significantly differs between patients with stroke and controls: 31/133 (23.3%) vs 11/133 (8.3%) (Odds ratio 3.4, 95% confidence interval 1.5 to 7.6, p < 0.001). Even after adjusting for matching variables and confounding risk factors (arterial hypertension, cardiac arrhythmia, and obesity), habitual snoring carries a significant risk factor for stroke (odds ratio: 2.9, 95% confidence interval 1.3 to 6.8 (p = 0.01)). The risk of ischaemic stroke was higher among older male patients with arterial hypertension who always snored. Habitual snoring was not significantly linked with sleep-related stroke nor with the pathophysiology of strokes. Inquiring about habitual snoring should become a routine practice, especially among older male patients with arterial hypertension, and specific preventive measures should be instituted at an earlier stage.

Adult↗