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Biomedical subjects

P Lévy

Publications and source records attributed to P Lévy.

At least 19 recordsLinked to original sources
PubMed2006

Arterial phase enhancement and body mass index are predictors of response to chemoembolisation for liver metastases of endocrine tumours.

Transcatheter arterial chemoembolisation (TACE) has been reported to be an efficient treatment of liver metastases of endocrine tumours in short series of patients. However, several factors seem to affect its results. The aim of this work is to identify predictors of response to TACE for liver metastases of endocrine tumours. A total of 163 TACE procedures were performed in 67 patients between 1994 and 2004. Forty-four patients were treated with streptozotocin and 23 with doxorubicin. Primary tumour was located in the pancreas for 19 patients, and had been removed in 43. Thirty-eight tumours were functioning. Response rate was 37% (confidence interval [CI] 95%: 28-49%). Median time to progression (TTP) was 14.5 months (CI 95%: 9-41). In multivariate analysis (n=43), predictors of tumour response were body mass index (BMI) (odds ratio [OR]: 1.3; CI 95%: 1.04-1.63; P=0.022), functioning type of tumour (OR: 7.31; CI 95%: 1.26-42.5; P=0.027), arterial phase enhancement on abdominal computed tomography (CT) (OR: 8.11; CI 95%:1.06-62; P=0.044) and use of streptozotocin for cytotoxic agent (OR: 21.3; CI 95%: 1.48-306; P=0.025). Analysis of TTP predictors showed that BMI (hazard ratio [HR]: 0.85; CI 95%: 0.76-0.86; P=0.01) and arterial phase enhancement (HR: 0.3; CI 95%: 0.12-0.73; P=0.008) were associated with delayed progression. This large study confirms the previously reported results of TACE regarding its efficacy for the treatment of liver metastases of endocrine tumours. Arterial phase enhancement on abdominal CT and BMI are predictors of treatment's efficacy. Streptozotocin should be the preferred cytotoxic agent in order to save anthracycline for systemic chemotherapy.

Adult↗
PubMed2006

Deleterious myocardial consequences induced by intermittent hypoxia are reversed by erythropoietin.

The aim of this work was to investigate the effects of different recombinant human erythropoietin (rhEPO) doses on the infarction development and if rhEPO could protect against the deleterious consequences induced by a previous intermittent hypoxia (IH, FiO(2) 5%, 4h). First, isolated rat hearts were submitted to an ischemia-reperfusion. rhEPO was infused before or after ischemia, at different doses. Secondly, rats were exposed to of IH. Twenty-four hours later, hearts underwent the ischemia-reperfusion protocol. For some hearts, 5Uml(-1) rhEPO was infused as previously. We observed that rhEPO has a dose-dependant effect on infarct size since it was significantly reduced by rhEPO infusions before or after ischemia. We also showed that 4h of IH induced a higher sensitivity to the infarction which was prevented by rhEPO. In conclusion, rhEPO administration before or after ischemia can protect isolated rat myocardium in a dose dependent manner and efficiently prevents the higher sensitivity to the infarction induced by previous intermittent hypoxia.

Animals↗
PubMed2006

Driving ability in sleep apnoea patients before and after CPAP treatment: evaluation on a road safety platform.

Sleepiness is considered to be the major cause of increased traffic accidents in patients with obstructive sleep apnoea syndrome (OSAS). Until now, OSAS patients' driving ability has been assessed using driving simulators, but no assessment in a more natural driving environment has been carried out to date. The aim of the present study was to evaluate driving parameters in OSAS and in controls on a road safety platform, and to compare them with attentional in-laboratory measures before and after continuous positive airway pressure treatment. The parameters measured were: reaction time; distance to stop and number of collisions on the platform; maintenance of wakefulness; and sustained, selective and divided attention in laboratory. Patients exhibited much longer reaction times than controls, leading to a lengthening of the vehicle's stopping distance of 8.8 m at 40 km.h(-1) and to twice the number of collisions. Patients did not demonstrate objective sleepiness or selective and sustained attention deficits. Divided attention deficits were found. However, they did not allow the prediction of real driving impairment. After CPAP treatment, there was no longer any difference between patients and controls regarding driving and attention performances. Driving abilities are significantly impaired in obstructive sleep apnoea syndrome. After continuous positive airway pressure treatment, deficits were normalised. This stresses the importance of evaluating attentional parameters in apnoeic patients and of offering continuous positive airway pressure treatment even to non-sleepy subjects.

Attention↗
PubMed2006

Clinical significance of P46L and R92Q substitutions in the tumour necrosis factor superfamily 1A gene.

OBJECTIVE: Tumour necrosis factor receptor-associated periodic syndrome (TRAPS) has been associated with several mutations in the TNF receptor super family 1A (TNFRSF1A), including most cysteine substitutions. However, the nature of two substitutions, P46L and R92Q, remains a topic of discussion. The aim of this study was to assess the actual role of these two sequence variations in a series of patients with TRAPS. METHODS: The main clinical data of 89 patients with TRAPS have been prospectively registered on a standard form. 84 patients or members of families with recurrent episodes of inflammatory symptoms spanning a period of more than 6 months and harbouring a TNFRSF1A mutation were studied. Clinical data have been analysed according to the nature of the mutation-P46L, R92Q or others. RESULTS: P46L is often seen in patients from Maghreb and is associated with a mild phenotype. P46L appears as a polymorphism with a non-specific role in inflammation. R92Q is associated with a variable phenotype and presents as a low-penetrance mutation. Interpreting these results will require a comparison with clinical signs and genetic background.

Adolescent↗
PubMed2006

Exhaled nitric oxide in single and repetitive prolonged exercise.

This study was performed to determine the influence of single and repetitive exercise on nitric oxide (NO) concentration in the lung. Exhaled NO concentration (FE(NO)) was measured during a constant-flow exhalation manoeuvre (170 ml x s(-1), against a 10 cmH2O resistance) in healthy individuals (a) during and after a 100-min square-wave exercise of between 25 and 60% of maximal power output (n = 18) and (b) before and after five successive prolonged exercises (90-120 min, 75-85% of maximal heart rate) separated by 48 or 24 h (n = 8). The FE(NO0.170) was decreased during and after the 100-min exercise test (mean +/- s(x): 58.5 +/- 3.7% and 76.7 +/- 5.2% of resting value at 90 min of exercise and 15 min post-exercise, respectively; P < 0.05). The five successive exercise sessions induced a similar post-exercise FE(NO0.170) decrement (73.1 +/- 2.9% of resting value 15 min post-exercise), while basal FE(NO0.170) values were not different between the five sessions (P > 0.05). These results suggest that prolonged exercise induces a reduction in NO concentration within the lung that lasts for several minutes after the end of exercise. However, repetitive exercises (at least every 24 h) allow complete NO recovery from one session to another. The implication of such a decrease in NO availability within the lung remains to be clarified.

Adult↗
PubMed2005

[Obstructive sleep apnea syndrome].

Obstructive sleep apnea syndrome is characterized by recurrent total or partial upper airway collapse during sleep. Although this disease affects more than 5% of general population, it remains largely undiagnosed. It is associated with an increase in cardiovascular risk and with a decrease in sustained attention that may cause automobile accidents or occupational injuries. Several simplified diagnostic tools (polysomnography) now allow easier diagnosis in a sleep laboratory or on an outpatient basis. Nasal continuous positive airway pressure remains the reference treatment, acting as a pneumatic splint that maintains airway patency. CPAP is effective in reducing daytime somnolence and controlling cardiovascular risk. Prosthetic management is an alternative to CPAP in cases of moderate sleep apnea with or without retrognathism in normal-weight patients. The effectiveness of surgery has not been proven, and it is indicated only in exceptional cases.

Humans↗
PubMed2005

Acute intermittent hypoxia improves rat myocardium tolerance to ischemia.

In this study, we investigated the influence of depth and duration of intermittent hypoxia (IH) on the infarct size development in isolated rat heart. The role of nitric oxide synthase (NOS) and ATP-sensitive K+ (K(ATP)) channel was also studied. Wistar male rats were exposed to IH [repetitive cycles of 1 min, 40 s with inspired oxygen fraction (FI(O2)), 5 or 10%, followed by 20-s normoxia], during 30 min or 4 h. Another group was exposed to 4 h of continuous hypoxia with 10% FI(O2). Twenty-four hours later, their hearts were isolated and subjected to a 30-min no-flow global ischemia-120-min reperfusion sequence. For some hearts, N(omega)-nitro-L-arginine methyl ester (L-NAME) (a nonselective inhibitor of NOS) or 5-hydroxydecanoic acid (5-HD) (a selective mitochondrial K(ATP) blocker) was infused before ischemia. Infarct size (in percentage of ventricles) was significantly reduced by prior IH for 4 h (10% FI(O2)) (21.8 +/- 3.1 vs. 33.5 +/- 2.5% in sham group). This effect was abolished by L-NAME or 5-HD. Infarct size was not different in groups subjected to either 30 min of IH or to continuous hypoxia compared with sham group. In contrast, IH for 4 h (5% FI(O2)) significantly increased infarct size (45.1 +/- 3.6 vs. 33.5 +/- 2.5% in sham group). Acute IH for 4 h with a minimal FI(O2) of 10% induced a delayed preconditioning against myocardial infarction in the rat, which was abolished by NOS inhibition and mitochondrial K(ATP) channel blockade. Depth, duration, and intermittence of hypoxia appeared to be critical for cardioprotection to occur.

Acute Disease↗
PubMed2005

Awake flow limitation with negative expiratory pressure in sleep disordered breathing.

BACKGROUND AND PURPOSE: Although upper airway collapsibility (UAC) is theoretically useful to anticipate severity of sleep-disordered breathing (SDB), inspiratory UAC measurements are poorly correlated with obstructive sleep apnea (OSA) severity. PATIENTS AND METHODS: We investigated in 15 healthy and 35 SDB awake subjects whether negative expiratory pressure (NEP) could be a technique which would allow us to anticipate SDB severity. We characterized in these subjects, both in supine and sitting position, at -5 and -10 cm H(2)O, the flow-volume curves and a new NEP quantitative index (ratio of the 'areas under the curve' of NEP flow-volume loop vs. spontaneous flow-volume loop). RESULTS: Abnormal flow-volume curves were significantly more frequent in patients with SDB than in healthy subjects, for both negative pressures in sitting posture and -10 cm H(2)O in supine position. The quantitative index decreased with the severity of SDB, independently of confounding factors (age, body mass index (BMI) and expiratory reserve volume (ERV)). In the supine position, at -5 and -10 cm H(2)O, thresholds of less than 160 and 180% respectively identified in 96.6% of SDB, whereas thresholds of greater than 160 and 180% were adequately classified in 76.9% of controls. CONCLUSIONS: NEP flow-volume curves and quantitative index during wakefulness are useful methods to detect UAC. These results, however, should be confirmed by a prospective study in the general population.

Adult↗
PubMed2005

[Alveolar hypoventilation during sleep and domiciliary assisted ventilation].

INTRODUCTION: An alveolar hypoventilation physiologically occurs during sleep and more specifically during REM sleep. STATE OF THE ART: During obstructive chronic respiratory failures, increases in PaCO2 that are associated with REM sleep can participate to the severity of daytime hypercapnia and in a subgroup of patients lead to an indication of nocturnal non-invasive ventilation (NIV) in association with the long-term oxygen therapy. A REM sleep hypoventilation generally appears during the early course of restrictive chronic respiratory failures. This REM sleep hypoventilation represents one of the most frequent reasons for initiating NIV in restrictive respiratory insufficiencies. Obesity-hypoventilation syndrome (OHS) refers to a hypercapnic chronic respiratory failure in which REM sleep hypoventilation is one of the main determinants. In France, in 2004, OHS is the primary chronic respiratory failure leading to at home NIV. NIV on OHS aims to maintain upper airway patency as sleep apnoea is frequently associated and to allow sufficient alveolar ventilation during REM sleep. PERSPECTIVES: Thus, sleep alveolar hypoventilation should be systematically assessed in obese patients and during the time curse evolution of all the chronic respiratory failures. This can be done relatively easily by using nocturnal oximetry concurrently with a transcutaneous PCO2 measurement. CONCLUSION: The understanding of exact mechanisms underlying abnormal respiratory events occurring during sleep allows optimising adjustments in NIV parameters.

Chronic Disease↗
PubMed2005

Exhaled nitric oxide during normoxic and hypoxic exercise in endurance athletes.

AIM: Endogenous nitric oxide (NO) through its relaxing effect on smooth muscle cells may be involved in pulmonary gas exchange as well as in the modulation of the hypoxic pulmonary vasoconstriction. As athletes with exercise-induced hypoxaemia (EIH) present pulmonary gas exchange abnormalities in normoxia that could be even greater in hypoxia, we hypothesized that pulmonary NO may be lower in such athletes with EIH. METHODS: Eleven athletes with EIH [decrease in arterial oxygen blood partial pressure (PaO2) > 12 mmHg] and 9 without EIH (NEIH) exercised at 40%, 60% (10 min) and 90% (5 min) of normoxic maximal power output (Pmax) in normoxia, and at 40% and 60% (10 min) of Pmax in hypoxia (FiO2 = 15%). Exhaled NO concentration during a constant flow exhalation (FENO(0.170)) and arterialized blood gases were measured at every power output. RESULTS: FENO(0.170) decreased from rest to exercise both in normoxia (-27.8 +/- 22.8% at 90% Pmax, P < 0.001) and hypoxia (-23.8 +/- 17.5% at 60% Pmax, P < 0.001). At 90% Pmax in normoxia, EIH athletes showed lower PaO2 (76.7 +/- 5.4 vs. 82.8 +/- 4.4 mmHg, P = 0.013) and greater FENO(0.170) decrement (-37.0 +/- 24.7% vs. -16.6 +/- 14.6%, P = 0.042) than NEIH athletes. During hypoxic exercise, P(a)O(2) and FENO(0.170) decreases were similar in both groups (P > 0.05). CONCLUSION: The present study shows lower pulmonary NO in athletes with gas exchange abnormalities during intense exercise in normoxia, while EIH and NEIH athletes have similar decreases in blood gases and pulmonary NO during hypoxic exercise. Decreased pulmonary NO in such conditions may contribute to ventilation-perfusion inequality and/or increase pulmonary vascular tone in athletes.

Adult↗
PubMed2005

A simple procedure for measuring pharyngeal sensitivity: a contribution to the diagnosis of sleep apnoea.

BACKGROUND: Patients with severe apnoea may have an impaired pharyngeal dilating reflex related to decreased pharyngeal sensitivity. The accuracy of a simple new procedure to measure pharyngeal sensitivity and to diagnose sleep disordered breathing (SDB) was investigated. METHODS: Pharyngeal disappearance and appearance sensory perception thresholds were measured by delivering different airflow rates on the soft palate using an intraoral device in 17 controls and 50 patients suffering from SDB evaluated by overnight polygraphy. The procedure was performed before (baseline) and after three successive administrations of a topical anaesthetic to sensitise the pharyngeal sensory impairment. Pharyngeal sensitivity was then evaluated according to SDB severity. SDB was classified as mild, moderate or severe according to the relative proportion of obstructive apnoeas-hypopnoeas and the amount of desaturation. RESULTS: Patients had higher baseline disappearance and appearance sensory thresholds than controls (mean (SD) 0.62 (0.44) v 0.26 (0.06) l/min and 0.85 (0.40) v 0.40 (0.19) l/min, p<0.001, respectively). Such differences were enhanced by topical anaesthesia. Impairment of pharyngeal sensitivity and the number of patients with impaired sensitivity increased from the least to the most severe SDB group as indicated by the test sensitivity for a respiratory disturbance index of >20/hour (50%, 73.7% and 88.5% in the mild, moderate, and severely affected groups, respectively). CONCLUSIONS: This simple and safe procedure showed that impairment of pharyngeal sensitivity is correlated with severity of SDB. Using this test in routine clinical practice may simplify the diagnosis of sleep apnoea, particularly for the most severe patients.

Adult↗
PubMed2005

Most obstructive sleep apnoea patients exhibit vigilance and attention deficits on an extended battery of tests.

Excessive daytime sleepiness, fatigue and altered attention are often experienced by obstructive sleep apnoea (OSA) patients. Although attentional problems are presumably responsible for part of the daytime functioning impairment in OSA, thorough investigation is unusual. Clinicians usually attribute these symptoms to somnolence. In clinical practice, only one isolated test is generally used to assess vigilance and attentional defects. It was hypothesised that most OSA patients exhibit a broad range of attentional deficits, beyond impaired maintenance of wakefulness, and a specific battery of tests is needed to correctly assess them. Three attentional tests were performed at 9:00, 11:00 and 13:30 h, measuring maintenance of wakefulness, sustained attention and divided attention. Twenty OSA patients (aged 51+/-12 yrs, apnoea/hypopnoea index 45+/-22 h) and 40 control subjects (aged 48.4+/-9.9 yrs) were tested. OSA patients performed significantly less well on the three tests than the controls at the three sessions. This battery of tests demonstrated that 95% of patients had vigilance and/or attentional impairment. Impairment patterns varied between patients. Vigilance is impaired in obstructive sleep apnoea patients over a wide range of attentional processes. Not only is their ability to remain awake in monotonous situations impaired but their ability to maintain attention in more stimulating conditions is also affected. A single test of vigilance is not sufficient and could underestimate impaired vigilance and attention in some patients.

Adult↗
PubMed2005

Overdrive atrial pacing does not improve obstructive sleep apnoea syndrome.

The aim of this study was to assess the ability of overdrive atrial pacing to reduce sleep apnoea severity. A total of 17 unselected patients (12 males; mean+/-SD age 71+/-10 yrs; body mass index 27+/-3 kg x m(-2)) who had received permanent atrial-synchronous ventricular pacemakers for symptomatic bradyarrhythmias and not known to have central or obstructive sleep apnoea syndrome (OSAS) were studied. Using a crossover study design, patients were or were not in pacing mode with atrial overdrive (15 beats x min(-1) faster than mean baseline nocturnal cardiac frequency) for 1 month. Patients were paced only during sleep periods, identified by a specific algorithm included in the pacemaker. Patients underwent three overnight polysomnographic evaluations 1 month apart. The first was performed for baseline evaluation. The patients were then randomly assigned to either 1 night in spontaneous rhythm or to 1 night in pacing mode with atrial overdrive. Two patients refused to continue the study after the first polysomnographic evaluation. OSAS was highly prevalent in this population: 10 of the 15 (67%) patients exhibited an apnoea-hypopnoea index of >30 events x h(-1). The nocturnal spontaneous rhythm was 59+/-7 beats x min(-1) at baseline, compared to 75+/-10 beats x min(-1) with atrial overdrive pacing. The apnoea-hypopnoea index was 46+/-29 events x h(-1) in spontaneous rhythm, compared to 50+/-24 events x h(-1) with atrial overdrive pacing. Overdrive pacing changed none of the respiratory indices, or sleep fragmentation or sleep structure parameters. In conclusion, atrial overdrive pacing has no significant effect on obstructive sleep apnoea.

Aged↗
PubMed2004

Chronic intermittent hypoxia increases infarction in the isolated rat heart.

Coronary heart disease is frequently associated with obstructive sleep apnea syndrome and treating obstructive sleep apnea appears to significantly improve the outcome in coronary heart disease. Thus we have developed a rat model of chronic intermittent hypoxia (IH) to study the influence of this condition on myocardial ischemia-reperfusion tolerance and on functional vascular reactivity. Wistar male rats were divided in three experimental groups (n = 12 each) subjected to chronic IH (IH group), normoxia (N group), or control conditions (control group). IH consisted of repetitive cycles of 1 min (40 s with inspired O(2) fraction 5% followed by 20 s normoxia) and was applied for 8 h during daytime, for 35 days. Normoxic cycles were applied in the same conditions, inspired O(2) fraction remaining constant at 21%. On day 36, mean arterial blood pressure (MABP) was measured before isolated hearts were submitted to an ischemia-reperfusion protocol. The thoracic aorta and left carotid artery were also excised for functional reactivity studies. MABP was not significantly different between the three experimental groups. Infarct sizes (in percent of ventricles) were significantly higher in IH group (46.9 +/- 3.6%) compared with N (26.1 +/- 2.8%) and control (21.7 +/- 2.1%) groups. Vascular smooth muscle function was similar in aorta and carotid arteries from all groups. The endothelium-dependent relaxation in response to acetylcholine was also similar in aorta and carotid arteries from all groups. Chronic IH increased heart sensitivity to infarction, independently of a significant increase in MABP, and did not affect vascular reactivity of aorta and carotid arteries.

Animals↗
PubMed2003

[Cardiovascular consequences of obstructive sleep apnea syndrome].

PURPOSE: This article is an update of past and current data on the relationship between obstructive sleep apnea syndrome and cardiovascular diseases. CURRENT KNOWLEDGE AND KEY POINTS: Obstructive sleep apnea syndrome is a common, but under-recognised, condition and should not be considered simplistically as the association of snoring and obesity. It may be suspected by the clinical history but a definite diagnosis requires the practice of polysomnography. Numerous studies have found a significant relationship between the presence of obstructive sleep apnea syndrome and the occurrence of cardiovascular events. Nonetheless, a definite causal relationship has only been established for the occurrence of hypertension. There are multiple immediate and delayed cardiovascular responses to the apneic events and thus there are many possible physiopathological mechanisms to explain the association of obstructive sleep apnea and cardiac and vascular events, the primary one being sympathetic hyperactivity. The prognosis of obstructive sleep apnea syndrome is closely related to the incidence of cardiovascular events. FUTURE PROSPECTS AND PROJECS: The existence of an independent relationship between obstructive sleep apnea syndrome and atherosclerosis is not yet demonstrated. The beneficial effects of continuous positive airway pressure, the treatment of choice for this condition, on the incidence of cardiovascular diseases remains to be confirmed although recent studies suggest that correct treatment of obstructive sleep apnea syndrome by continuous positive airway pressure may reduce the cardiovascular risk and in particular that of hypertension.

Arteriosclerosis↗
PubMed2002

Differential diagnosis between chronic pancreatitis and pancreatic cancer: value of the detection of KRAS2 mutations in circulating DNA.

KRAS2 mutations in codon 12 have been detected in about 80% of pancreatic cancers. The aim of this study was to evaluate the value of KRAS2 mutations detection in circulating deoxyribo nucleic acid to differentiate pancreatic cancer from chronic pancreatitis. Circulating deoxyribonucleic acid was isolated from serum in 47 patients with histologically proven pancreatic adenocarcinomas (26 males, median age 65 years) and 31 controls with chronic pancreatitis (26 males, median age 48 years). Mutations at codon 12 of KRAS2 gene were searched for using polymerase chain reaction and allele specific amplification. Serum carbohydrate antigen 19.9 levels were also determined. KRAS2 mutations were found in 22 patients (47%) with pancreatic cancer and in four controls with chronic pancreatitis (13%) (P<0.002). None of the latter developed a pancreatic cancer within the 36 months of median follow-up. The sensitivity, specificity, positive and negative predictive values of serum serum KRAS2 mutations for the diagnosis of pancreatic cancer were 47, 87, 85 and 52%, respectively. KRAS2 mutations were not related to age, gender, smoking habit, tumour stage, or survival. Among the 26 patients with normal or non-contributive (due to cholestasis) serum carbohydrate antigen 19.9 levels, 14 (54%) had KRAS2 mutations. The combination of KRAS2 and carbohydrate antigen 19.9 gave a sensitivity, specificity, positive and negative predictive values for the diagnosis of pancreatic cancer of 98, 77, 87 and 96%, respectively. Detection of KRAS2 mutations in circulating deoxyribo nucleic acid has a low sensitivity but a specificity about 90% for the diagnosis of pancreatic cancer. It seems particularly useful when serum carbohydrate antigen 19.9 levels are normal or inconclusive. A combined normal serum carbohydrate antigen 19.9 and absence of circulating KRAS2 mutations makes the diagnosis of pancreatic cancer extremely unlikely.

Adenocarcinoma↗