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Biomedical subjects

F Barbé

Publications and source records attributed to F Barbé.

At least 19 recordsLinked to original sources

Antioxidant status in patients with sleep apnoea and impact of continuous positive airway pressure treatment.

The episodes of hypoxia/re-oxygenation associated with the respiratory disturbances observed in patients with obstructive sleep apnoea syndrome (OSAS) may induce the generation of oxygen free radicals. Indeed, several studies suggest that OSAS is associated with oxidative stress. The present study tested the hypothesis that patients with OSAS have an alteration in antioxidant defences. The plasma levels of total antioxidant status (TAS), glutathione peroxidase (GPX), gamma-glutamyltransferase (GGT), vitamins A, E, B12 and folate, and homocysteine were determined in 47 patients with OSAS and 37 healthy subjects. Of these, 27 patients who used continuous positive airway pressure (CPAP) for >4 h.night-1 were re-examined 12 months later. Patients with OSAS had lower TAS (1.4+/-0.16 versus 1.50+/-0.10 mmol.L-1), vitamin A (64+/-19 versus 74+/-17 microg.dL-1) and vitamin E levels (1,525+/-499 versus 1,774+/-503 microg.dL-1), and increased values of GGT (42+/-22 versus 32+/-16 U.L-1) than controls. There was no difference between groups in GPX, homocysteine, vitamin B12 and folate plasma levels. CPAP treatment normalised the levels of TAS (1.50+/-0.13 mmol.L-1) and the activity of GGT (30+/-14 U.L-1) without any influence on vitamins levels. In conclusion, the results indicate that patients with obstructive sleep apnoea syndrome have a decreased antioxidant capacity that is partially reversed by continuous positive airway pressure treatment.

Adult↗

Homocysteine and methylmalonic acid concentrations in cerebrospinal fluid: relation with age and Alzheimer's disease.

BACKGROUND: Homocysteine may be involved in the pathogenesis of late onset Alzheimer's disease. It is implicated in the metabolism of several important pathways in the brain. Methylmalonic acid (MMA) is related to the metabolism of branched chained amino acids and fatty acids. OBJECTIVES: To compare cerebrospinal fluid (CSF) total homocysteine and MMA in elderly subjects, patients with Alzheimer's disease, and younger healthy controls. SUBJECTS: CSF samples were obtained from 33 patients under 20 years of age; 28 patients aged 21 to 60 years; 22 normal elderly subjects aged over 60; and 38 Alzheimer patients aged over 60. RESULTS: CSF total homocysteine increased with age (mean (SD): 57 (35) nmol/l in the youngest group v 123 (89) nmol/l in the elderly group (p<0.001)). There was no difference between the elderly group and Alzheimer patients (115 (62) nmol/l). CSF MMA did not differ in the elderly group and the Alzheimer group (38 (13) v 35 (14) ng/ml). In the youngest group, it was significantly higher (60 (15) ng/ml). CONCLUSIONS: CSF total homocysteine is not increased in Alzheimer's disease compared with age matched controls. CSF total homocysteine was correlated with age. The decrease in CSF MMA levels with age eliminates a lack of vitamin B-12 at neuronal level.

Adult↗

Effects of obesity upon genioglossus structure and function in obstructive sleep apnoea.

Obesity is a common feature of the obstructive sleep apnoea syndrome. It can influence the structure and function of skeletal muscles. However, its effects upon the upper airway muscles have not been explored directly. This study assessed the structure and function of the genioglossus in patients with obstructive sleep apnoea syndrome and in healthy subjects (with and without obesity, defined by a body mass index > 30 kg x m(-2)). Further, to investigate the effects of continuous positive airway pressure (CPAP) treatment, patients with obstructive sleep apnoea syndrome after at least 1 yr under CPAP were also studied. The study found that obese and nonobese patients showed different in vitro geniglossus endurance properties. In obese patients, geniglossus endurance was indistinguishable from normal while, nonobese patients, at diagnosis, showed increased genioglossus fatigability; this was not observed in patients treated with CPAP. By contrast, patients with obstructive sleep apnoea syndrome showed at diagnosis a higher percentage of type II fibres than controls and patients under CPAP treatment independently of obesity. This difference is mainly due to a predominance of subtype IIb fibre. This difference was not observed in the group of patients treated with CPAP. Genioglossus twitch force was normal in all patients. These results suggest that different pathogenic mechanisms may underlie the development of obstructive sleep apnoea syndrome in obese and nonobese patients. This observation may have potential clinical implications.

Adult↗

[Steady car engine noise does not affect the cognitive abilities of sleep apnea syndrome patients].

Traffic accidents are more frequent for sleep apnea syndrome (SAS) patients than in the population at large. The mechanisms that underlie this observation are poorly defined. Our working hypothesis was that in SAS patients the steady noise of a car engine might alter cognitive capacities that may be involved in driving, thus increasing the risk of traffic accidents. To test this hypothesis we designed a prospective randomized controlled trial. Eighteen SAS patients (apnea-hypopnea index [SEM] 62 [6] h1) and 18 healthy controls were studied. All the participants were evaluated in random order both in basal conditions and after exposure to the steady noise of a car engine recorded on a compact disc. Their level of vigilance was evaluated (Steer-Clear) as well as their reaction time (PVT 192). Attention, coordination, and memory were measured using the following tests: Wechsler Memory Scale (digit span), the Wechsler Intelligence Scale (digit symbol), and Lezack's Trail Making tests A and B. The SAS patients were slightly younger than the control group (mean 50 [7] vs 57 [11] years, respectively; P=.05). The patients showed a lower level of vigilance than the controls both in basal and engine noise conditions (P<.05). No differences between groups were found for the other variables studied. Exposure to steady car engine noise had no effect on the tests of either group. In conclusion, the results of our study do not support the hypothesis that steady car engine noise significantly alters the cognitive ability of SAS patients.

Accidents, Traffic↗

Plasminogen activator inhibitor-I (PAI-I) polymorphisms in patients with obstructive sleep apnoea.

Cardiovascular diseases are frequent among patients with the obstructive sleep apnoea syndrome (OSAS), The aetiopathogenesis of this association is unclear. Type 1 plasminogen activator inhibitor (PAI-1) is one of the primary regulators of the fibrinolytic system. A reported association between PAI-1 activity and an insertion/deletion polymorphism (4G/5G) in the promoter region of the PAI-1 gene suggests a critical role for this genomic region in the pathogenesis of several cardiovascular diseases. In this study, we determined the prevalence of this polymorphism in patients with OSAS and in healthy control subjects. The 4G/5G polymorphism in the promoter region of the PAI-1 gene was determined in 78 male patients with severe OSAS (56 +/- 2 apnoeas per hour) and in 70 healthy male, non-smoker volunteers of similar age, without personal or familial history of cardiovascular disease. The frequency ofthe 4G/4G, 4G/5G and 5G/5G genotypes in patients with OSAS (18%, 62%, 19%, respectively) was not significantly different from that seen in healthy subjects (16%, 60%, 24% P=NS). These results show that the distribution of the 4G/5G polymorphism in the promoter region ofthe PAI-1 gene in patients with OSAS is similar to that observed in healthy subjects. This observation suggests that the PAI-1 polymorphism has no relationship with the increased risk of cardiovascular diseases seen in patients with OSAS.

Case-Control Studies↗

Effectiveness of continuous positive airway pressure in mild sleep apnea-hypopnea syndrome.

The aim of this trial was to evaluate the effectiveness of continuous positive airway pressure (CPAP) in patients with mild sleep apnea- hypopnea syndrome (SAHS). One hundred forty-two consecutive patients with mild SAHS (apnea-hypopnea index 10-30, without severe sleepiness) were randomly assigned to receive conservative treatment (CT)-sleep hygiene and weight loss-(65 patients) or CT plus CPAP (77 patients), and 125 patients (86% males, age: 54 +/- 9 yr, BMI: 29 +/- 4 kg/m(2), AHI: 20 +/- 6, ESS: 12 +/- 4) completed the follow-up. The following outcomes were assessed at inclusion and after 3 and 6 mo of treatment: sleepiness (Epworth scale, multiple sleep latency test [MSLT]), other symptoms related to SAHS, cognitive function, and perceived health status (Functional Outcomes of Sleep Questionnaire [FOSQ], Nottingham Health profile). The relief of SAHS-related clinical symptoms was significantly greater in the CPAP group than in the CT group; the Epworth scale and FOSQ also showed more improvement in the CPAP group but did not reach significance. There were no significant differences in the other tests performed probably because the baseline values were normal. CPAP compliance was 4.8 +/- 2.2 h and treatment continuation was accepted by 62% of the patients at the end of the study. These results suggest that CPAP can be considered in treating patients with mild SAHS on the basis of an improvement in symptoms.

Chi-Square Distribution↗

Treatment with continuous positive airway pressure is not effective in patients with sleep apnea but no daytime sleepiness. a randomized, controlled trial.

BACKGROUND: The sleep apnea-hypopnea syndrome is defined by a pathologic number of respiratory events during sleep (the apnea-hypopnea index, defined as the number of apnea and hypopnea episodes per hour) and daytime symptoms (mostly, excessive sleepiness). In patients with the sleep apnea syndrome, treatment with continuous positive airway pressure (CPAP) normalizes both the apnea-hypopnea index and diurnal symptoms. However, the effect of CPAP in persons with a pathologic apnea-hypopnea index without daytime sleepiness is unclear. OBJECTIVE: To investigate the short-term effects of CPAP on quality of life, objective sleepiness, cognitive function, and arterial blood pressure in nonsleepy patients with a pathologic apnea-hypopnea index. DESIGN: Multicenter randomized, placebo-controlled, parallel-group study. SETTING: Six teaching hospitals in Spain. PATIENTS: 55 patients with an apnea-hypopnea index of 30 or greater who did not have daytime sleepiness (Epworth Sleepiness Scale score </= 10). INTERVENTION: Patients were randomly assigned to receive optimal (n = 29) or sham (n = 25) CPAP and were observed for 6 weeks. MEASUREMENTS: Quality of life, objective sleepiness (Multiple Sleep Latency Test score), cognitive function, and arterial blood pressure. RESULTS: The intervention and control groups were similar in terms of mean (+/-SE) age (54 +/- 2 vs. 52 +/- 2 years), apnea-hypopnea index (54 +/- 3 vs. 57 +/- 4), Epworth Sleepiness Scale score (7.0 +/- 0.4 vs. 7.0 +/- 0.4) and adherence to CPAP treatment (5.0 +/- 0.4 vs. 4.0 +/- 0.5 hours/d). Other variables, such as quality of life, cognitive function, and arterial blood pressure, were also similar in both groups before treatment. After 6 weeks of CPAP or sham CPAP, none of these variables changed significantly. CONCLUSION: In patients with an apnea-hypopnea index of 30 or greater and no subjective daytime sleepiness, CPAP does not modify quality of life, objective sleepiness, vigilance, attention, memory, information processing, visuomotor coordination, or arterial blood pressure. Treatment with CPAP is therefore not indicated in nonsleepy patients with a pathologic apnea-hypopnea index.

Blood Pressure↗

Detection of moderate hyperhomocysteinemia: comparison of the Abbott fluorescence polarization immunoassay with the Bio-Rad and SBD-F high-performance liquid chromatographic assays.

The importance of accurate methods for homocysteine measurement has been emphasized. We compared the results obtained with the most commonly used high-performance liquid chromatography (HPLC) assay, and two recently commercially available methods: another HPLC and a fluorescence polarization immunoassay, in plasmas from normo- or hyperhomocysteinemic patients. A significant agreement between the different methods in classifying the results as hyper or normal-homocysteinemia was observed. However, a significant difference between the results was found. Standardization is urgently necessary to improve the concordance of homocysteine determination.

Chemistry, Clinical↗

QT interval lengthening in premature infants treated with doxapram.

OBJECTIVE: Doxapram, routinely used in premature infants treated for apnea of prematurity unresponsive to methylxanthines, has been related to cardiac conduction disorders. This study was designed to evaluate doxapram cardiac and general tolerance and its relationship to drug plasma concentrations in very premature infants. METHODS: Forty infants (mean +/- SEM, 28.9 +/- 0.3 weeks of gestation) who were given intravenous doxapram, 0.5 to 1 mg/kg per hour, at 15.9 +/- 2.4 days of life were evaluated prospectively. Electrocardiograms were monitored before and during the first 3 days of treatment. QT interval corrected for heart rate (QTc) longer than 440 ms was regarded as clinically pertinent, given that it is considered a significant risk of conduction disorder leading to torsades de pointes and sudden death. Other side effects were recorded. Toxic plasma concentration of doxapram and ketodoxapram was set at >4 mg/L. RESULTS: A statistically significant but moderate lengthening of QTc interval has been observed from 394 +/- 4 ms before doxapram to 409 +/- 4 ms at 48 and 72 hours of treatment (P =.0065). For 6 patients, QTc interval became longer than 440 ms without any other rhythm or conduction disorder. Digestive disorders were observed in 20 infants but 9 presented with concomitant septicemia. No relationship was found between presence or absence of adverse effects and drug plasma concentrations. CONCLUSION: Our study enlightened the lengthening effect of doxapram on QTc interval in premature infants with a risk of exceeding the 440 ms threshold that is considered life-threatening. This finding emphasizes the need for electrocardiogram follow-up when using doxapram in neonates.

Caffeine↗

Angiotensin converting enzyme in patients with sleep apnoea syndrome: plasma activity and gene polymorphisms.

The prevalence of several cardiovascular diseases is increased with obstructive sleep apnoea syndrome (OSAS), due to, as yet, unclear reasons. Angiotensin converting enzyme (ACE) abnormalities have been implicated in the pathogenesis of various cardiovascular diseases. In this study, plasma ACE activity and the distribution of an insertion (I)/deletion (D) polymorphism of the ACE gene were determined in OSAS patients and in healthy controls. A total of 63 patients with OSAS (mean+/-SEM 54.5+/-2.5 apnoea/hypopnoeas.h(-1)) and 32 healthy subjects were studied. To avoid potential confounding factors, patients treated with ACE inhibitors or continuous positive airway pressure were excluded, as well as controls in whom a blood sample was not obtained early in the morning. ACE activity was determined spectrophotometrically in 46 OSAS patients and 25 controls. The I/D ACE polymorphism was determined by polymerase chain reaction in 44 patients and 32 controls. ACE activity was higher in OSAS patients (53.9+/-2.5 IU.L(-1)) than in healthy controls (42.4+/-3.1 IU.L(-1), p<0.01). This was independent of the presence of arterial hypertension. The frequency distribution of the DD, II and ID genotypes in OSAS patients (30%, 16%, 54%, respectively) was not significantly different from that seen in healthy subjects (31%, 28%, 41%, respectively, p=0.356). These results indicate that ACE plasma activity is increased in untreated OSAS patients. This increased activity may contribute to the pathogenesis of the cardiovascular disease in these patients.

Cardiovascular Diseases↗

The effect of 677C-->T and 1298A-->C mutations on plasma homocysteine and 5,10-methylenetetrahydrofolate reductase activity in healthy subjects.

We have studied the effect of common mutations (677C-->T and 1298A-->C) of the methylenetetrahydrofolate reductase (MTHFR) gene in sixty-six healthy French subjects, aged 27-47 years. Serum folate, vitamin B12, and plasma total homocysteine were measured as well as the specific activity of MTHFR in lymphocytes. The frequency of subjects homozygous for the 677TT genotype was 18%, and that of those homozygous for the 1298CC genotype was 12.5%. The frequency of individuals heterozygous for both mutations was 23.5%. The 1298A-->C mutation was associated with decreased MTHFR specific activity in subjects with both 677CC and 677CT genotypes. This activity was 60% for the 677CC/1298AC genotype and 52% for the 677CC/1298CC genotype when compared with the MTHFR specific activity of the 677CC/1298AA genotype. Heterozygotes for both mutations (677CT/1298AC genotype) had 36% of the reference specific activity. Although homocysteine levels in 677TT and 1298CC genotype subjects were higher than for other genotypes, no significant differences were observed among different genotypes. This may be due to high serum folate level in our samples, and suggests that folate therapy may be useful to prevent hyperhomocysteinaemia in homozygous mutant subjects.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗

Long-term effects of CPAP on daytime functioning in patients with sleep apnoea syndrome.

Daytime sleepiness, impaired cognitive performance and dysphoric mood are often present in patients with obstructive sleep apnoea syndrome (SAS). This prospective controlled study evaluates the effects of treatment with continuous positive airway pressure (CPAP) during 1 yr on daytime functioning in a large group of patients with SAS. The authors studied 80 patients (mean+/-sem 49+/-1 yrs) with SAS with a mean apnoea-hypopnoea index of 60+/-2 h-1, and 80 healthy control subjects matched for sex and age (46+/-1 yrs.). Measurements were obtained at the beginning of the study and 12+/-1 months later, and included: daytime sleepiness (Epworth scale), depression and anxiety (Beck tests), vigilance (Steer-Clear) and reaction time (Psychometer Vigilance Test 192). Drug, coffee and alcohol intake, as well as the sleep schedule, were also recorded. Results showed that, before treatment, patients were more somnolent (p<0.001), anxious (p<0.01) and depressed (p<0.001) than control subjects. Also, they had a longer reaction time (p<0.05) and poorer vigilance (p<0.01). The use of CPAP improved significantly the levels of somnolence (p<0.0001) and vigilance (p<0.01), but failed to modify anxiety and depression. Reaction time changes were minor. Variables with a potential confounding effect did not change during the study. These results provide firm evidence to substantiate the use of continuous positive airway pressure in patients with sleep apnoea syndrome.

Analysis of Variance↗

Abnormal lipid peroxidation in patients with sleep apnoea.

The prevalence of cardiovascular diseases is increased in patients with the obstructive sleep apnoea syndrome (OSAS). The fall and rise of arterial oxygenation that follows each apnoea may increase lipid peroxidation and contributes to explaining this association. In the present study, the authors determined lipid peroxidation in patients with OSAS and the effect of treatment with continuous positive airway pressure (CPAP). Fourteen male patients with severe OSAS (59+/-5 apnoea x h(-1)) (+/-SEM) and 13 healthy nonsmoking, male volunteers of similar age were studied. Patients were studied at diagnosis and after treatment with CPAP for more than 1 yr (>4 h x night(-1)). A venous blood sample was obtained early in the morning after fasting all night. In patients with OSAS, a sample before and during sleep was also obtained. Low density lipoprotein (LDL) particles were isolated by sequential ultracentrifugation. Their level of oxidation was determined by the thiobarbituric acid assay (TBARs), and their susceptibility to oxidation by the lag phase measurement. Patients with OSAS showed higher TBARs (28.1+/-2.8 versus 20.0+/-1.8 nmol x malondialdehyde x mgLDL protein(-1), p=0.02) and shorter lag phase values (83.8+/-3.4 versus 99.7+/-3.4 min, p=0.005) than controls. These differences were not due to the smoking status of the patient. Likewise, these values did not change significantly throughout the night yet, the lag phase value was significantly improved by treatment with CPAP (124.9+/-8.5 min; p<0.001). These results indicate that obstructive sleep apnoea syndrome is associated with abnormal lipid peroxidation and that this is improved by chronic use of Continuous positive airway pressure. These results can contribute towards explaining the high prevalence of cardiovascular diseases seen in Obstructive sleep apnoea syndrome.

Adult↗