Biomedical subjects

Maurice Lamy

Publications and source records attributed to Maurice Lamy.

17 recordsLinked to original sources

PubMed2006

Brain response to one's own name in vegetative state, minimally conscious state, and locked-in syndrome.

BACKGROUND: A major challenge in the management of severely brain-injured patients with altered states of consciousness is to estimate their residual perception of the environment. OBJECTIVE: To investigate the integrity of detection of one's own name in patients in a behaviorally well-documented vegetative state (VS), patients in a minimally conscious state (MCS), and patients with locked-in syndrome. DESIGN: We recorded the auditory evoked potentials to the patient's own name and to 7 other equiprobable first names in 15 brain-damaged patients. RESULTS: A P3 component was observed in response to the patient's name in all patients with locked-in syndrome, in all MCS patients, and in 3 of 5 patients in a VS. P3 latency was significantly (P<.05) delayed for MCS and VS patients compared with healthy volunteers. CONCLUSIONS: These results suggest that partially preserved semantic processing could be observed in noncommunicative brain-damaged patients, notably for the detection of salient stimuli, such as the subject's own name. This function seems delayed in MCS and (if present) in VS patients. More important, a P3 response does not necessarily reflect conscious perception and cannot be used to differentiate VS from MCS patients.

Acoustic Stimulation↗

PubMed2005

Acute neutrophil activation in direct stenting: comparison of stable and unstable angina patients.

BACKGROUND: Polymorphonuclear neutrophils have been implicated in the pathophysiology of atherosclerosis. A substantial body of evidence has emerged to implicate the role of specific leucocyte derived enzyme myeloperoxidase in atherogenesis, since its initiation through progression until destabilization. The aim of the study was to determine the presence of polymorphonuclear neutrophils activation after coronary stenting, to compare this activation between stable and unstable setting and to evaluate the kinetic relation of this activation with inflammatory response following atherosclerotic plaque rupture. METHODS: Myeloperoxidase, lactoferrin, elastase, C-reactive protein and cytokine plasma levels were assessed in 15 patients undergoing direct coronary stenting for unstable angina (Group A) and compared to 11 patients undergoing this procedure for stable angina (Group B). Serial sampling starting before arteriography and continued for 24 h was carried out in all patients. RESULTS: A significant elevation in myeloperoxidase and lactoferrin levels was observed after stenting in both group A (p<0.0001) and group B (p<0.0001), but was higher in group A. Interleukin-8, interleukin-12 and interleukin-6 levels increased temporarily after stenting in the 2 groups. Baseline values of C-reactive protein were similar in the 2 groups and a progressive increase was observed after the intervention. CONCLUSIONS: Direct coronary artery stenting is associated with an early polymorphonuclear neutrophils activation followed by release of inflammatory cytokines (interleukin-6, interleukin-8, interleukin-12) and C-reactive protein elevation in both stable and unstable patients. We conclude that stenting by itself is associated with myeloperoxidase liberation with a significantly enhanced response in unstable patients.

Adult↗

PubMed2005

Resveratrol and curcumin reduce the respiratory burst of Chlamydia-primed THP-1 cells.

The intracellular bacterium Chlamydia pneumoniae is involved in the inflammation process of atherosclerosis. We previously demonstrated that C. pneumonia infected monocytes (THP-1 cells) responded to stimulation by an increased respiratory burst linked to an increased NADPH oxidase (NOX) activity. We now tested agents acting on the assembly of the NOX subunits or on protein kinase C, a trigger of NOX activity. Apocynin, resveratrol, rutin, quercetin, curcumin, and tocopherols were tested. The cells were pre-incubated with Chlamydia and the agent for 19 h, and then stimulated with phorbol myristate acetate. The NOX activity was monitored by measuring the hydrogen peroxide production. Resveratrol and curcumin (10(-4)-10(-6) M) were better inhibitors than apocynin. alpha-Tocopherol was inactive, and gamma-tocopherol inhibitor at 10(-4) M only. Quercetin was inactive, and rutin a moderate but significant inhibitor. The inhibition by resveratrol was increased by 10(-6) M rutin or quercetin. Resveratrol and curcumin thus appeared to be interesting for atherosclerosis treatment.

Antioxidants↗

PubMed2005

Catalytic activation of copper (II) salts on the reaction of peroxynitrite with propofol in alkaline medium.

We report here on the role of copper (II) salts on the acceleration of peroxynitrite (ONOO-) decomposition and ONOO- reaction with the anaesthetic agent propofol (2,6-diisopropylphenol) in alkaline medium. We observed a strong acceleration of the ONOO- decomposition in alkaline medium in the presence of copper (I and II) salts. After 18 h of ONOO- reaction with propofol, we observed nitrosated, nitrated, and oxidized (quinone and diphenylquinone) derivatives of propofol, but in the presence of Cu(II) (20% molar vs ONOO-), the yields of quinone and nitrosopropofol strongly increased. We also observed that the temperature and the atmosphere influenced the effects of Cu(II) on ONOO- reactions with propofol: low temperatures promoted nitrosation and high temperatures promoted oxidation; O2 atmosphere increased the general reactivity and the yield of nitrated and oxidized products. We highlighted the influence of Cu(II) salts on the radical character of the reaction by direct EPR technique. The exact mechanism of the Cu(II) catalysis remains unexplained, but we suggest the formation of a copper complex with propofol or, more probably, the oxidation of ONOO- into ONOO. by copper ions promoting the formation of quinone and nitrosopropofol according to a previously reported mechanism [M. Cudic, C. Ducrocq, Transformations of 2,6-diisopropylphenol by NO-derived nitrogen oxides, particularly peroxynitrite, Nitric Oxide 4 (2000) 147-156].

Alkalies↗

PubMed2005

The locked-in syndrome : what is it like to be conscious but paralyzed and voiceless?

The locked-in syndrome (pseudocoma) describes patients who are awake and conscious but selectively deefferented, i.e., have no means of producing speech, limb or facial movements. Acute ventral pontine lesions are its most common cause. People with such brainstem lesions often remain comatose for some days or weeks, needing artificial respiration and then gradually wake up, but remaining paralyzed and voiceless, superficially resembling patients in a vegetative state or akinetic mutism. In acute locked-in syndrome (LIS), eye-coded communication and evaluation of cognitive and emotional functioning is very limited because vigilance is fluctuating and eye movements may be inconsistent, very small, and easily exhausted. It has been shown that more than half of the time it is the family and not the physician who first realized that the patient was aware. Distressingly, recent studies reported that the diagnosis of LIS on average takes over 2.5 months. In some cases it took 4-6 years before aware and sensitive patients, locked in an immobile body, were recognized as being conscious. Once a LIS patient becomes medically stable, and given appropriate medical care, life expectancy increases to several decades. Even if the chances of good motor recovery are very limited, existing eye-controlled, computer-based communication technology currently allow the patient to control his environment, use a word processor coupled to a speech synthesizer, and access the worldwide net. Healthy individuals and medical professionals sometimes assume that the quality of life of an LIS patient is so poor that it is not worth living. On the contrary, chronic LIS patients typically self-report meaningful quality of life and their demand for euthanasia is surprisingly infrequent. Biased clinicians might provide less aggressive medical treatment and influence the family in inappropriate ways. It is important to stress that only the medically stabilized, informed LIS patient is competent to consent to or refuse life-sustaining treatment. Patients suffering from LIS should not be denied the right to die - and to die with dignity - but also, and more importantly, they should not be denied the right to live - and to live with dignity and the best possible revalidation, and pain and symptom management. In our opinion, there is an urgent need for a renewed ethical and medicolegal framework for our care of locked-in patients.

Consciousness↗

PubMed2005

Early release of neutrophil markers of activation after direct stenting in patients with unstable angina.

OBJECTIVE: To assess polymorphonuclear neutrophils activation after stenting in acute coronary syndromes studied by myeloperoxydase, lactoferrin and elastase release in this clinical setting. METHODS: Myeloperoxydase, lactoferrin, elastase, C-reactive protein and cytokines serum levels were assessed in 20 patients undergoing catheterization for unstable angina. Serial sampling starting before arteriography and continued up to 24 h was carried out in 15 patients undergoing direct stenting (group A) and in five patients assessed by coronary angiography only (group B). RESULTS: Myeloperoxydase, lactoferrin and elastase levels remained unchanged following catheterization, whereas a significant increase in myeloperoxydase (P = 0.0009) and lactoferrin (P = 0.004) was observed after stenting. No change in levels of tumour necrosis factor alpha, interleukin (IL)-8 and IL-11 was found in group B after catheterization at the different sampling times, although IL-8 and IL-11 levels increased transiently following stenting. IL-6 values increased in both groups. Baseline values of C-reactive protein were similar in each group. A progressive increase in C-reactive protein was noted in both groups and appeared to be larger following stenting (group A: P = 0.0002; group B: P = 0.01). CONCLUSIONS: In patients with unstable angina, stenting is associated by immediate neutrophil activation followed by release of inflammatory cytokines (IL-6, IL-8, IL-11) and C-reactive protein elevation. This study points out a potential role of myeloperoxydase as a trigger for inflammatory reaction in patients with unstable coronary syndromes undergoing percutaneous coronary intervention.

Adult↗

PubMed2005

Liver transplantation in Jehovah's witnesses.

For religious reasons, Jehovah's witnesses refuse transfusion of blood products (red cells, platelets, plasma), but may accept organ transplantation. The authors developed a multidisciplinary protocol for liver transplantation in Jehovah's witnesses. In a 6-year period, nine Jehovah's witness patients were listed for liver transplantation. They received preoperative erythropoietin therapy, with iron and folic acid that allowed significant haematocrit increase. Two patients underwent partial spleen embolization to increase platelet count. Seven patients underwent cadaveric whole liver transplantation, and two right lobe living-related liver transplantation, using continuous circuit cell saving system and high dose aprotinin. No patient received any blood product during the surgical procedure. One patient suffering from deep anaemia after living-related liver transplantation was transfused as required by his family, but died from aspergillus infection. One 6-year-old child was transfused against her parent's will. The authors demonstrated that it is possible to increase haematocrit and platelet levels in cirrhotic patients awaiting liver transplantation. They were able to reduce intraoperative need for blood products, allowing liver transplantation in prepared Jehovah's witness patients. This experience may be beneficial for non-Jehovah's witness liver transplant recipients.

Adolescent↗

PubMed2004

Effects of COX-2 inhibitors on ROS produced by Chlamydia pneumoniae-primed human promonocytic cells (THP-1).

Chronic inflammation through foam cells and macrophages is important in atherosclerosis development, and can be considered as therapeutic targets. Cyclooxygenase and NADPH-oxidase were expressed within atherosclerotic lesions. Reactive oxygen species produced by NADPH oxidase were found to trigger the cyclooxygenase-2 expression. The effects of preferential COX-2 inhibitors on ROS produced by Chlamydia-primed human monocytes (THP-1 cells) were evaluated by fluorescence, chemiluminescence, oxymetry, and EPR spin trapping. Fluorescence assays showed an increased production of ROS with Chlamydia versus cells primed by 10(-8)M PMA. COX-2 inhibitors inhibited in a dose-dependent manner the luminol-enhanced CL while ibuprofen and diclofenac increased the chemiluminescence response. By EPR spin trapping, COX-2 inhibitors, ibuprofen, and diclofenac, exhibited a dose-dependent inhibiting effect (10 and 100muM) on the EPR signal appearance. Our cell model combining EPR, chemiluminescence, and oxymetry appeared relevant to study the modulating effects of preferential COX-2 inhibitors on the cell oxidant activity and chronic inflammatory diseases.

Arteriosclerosis↗

PubMed2004

Propofol scavenges reactive oxygen species and inhibits the protein nitration induced by activated polymorphonuclear neutrophils.

Activated polymorphonuclear neutrophils may damage tissues through the release of biochemical mediators. Among them, peroxynitrite is responsible for hydroxylation reactions and nitration of proteins, or is metabolised into nitrate. We investigated the effect of propofol on the production of reactive oxygen species, the nitration of proteins and the formation of nitrate by activated human polymorphonuclear neutrophils. Propofol dose-dependently inhibited chemiluminescence, nitration of proteins and nitrate production in a concentration range from 10(-3) to 10(-6) mM. A significant correlation was observed between the logarithm of propofol concentration and the intensity of chemiluminescence (r2=0.90), the nitration of proteins (r2=0.67) and the production of nitrate (r2=0.79). Those results are consistent with the scavenging effect of propofol on peroxynitrite and could confer a protective property to propofol in pathological situations involving polymorphonuclear neutrophils activation.

Dose-Response Relationship, Drug↗

PubMed2004

Effects of glucocorticoids on the respiratory burst of Chlamydia-primed THP-1 cells.

We previously observed that the respiratory burst of human monocytes (THP-1 cell line) triggered by phorbol myristate acetate was strongly enhanced by a priming of the cells by Chlamydia pneumoniae [Biochem. Biophys. Res. Commun. 287 (2001) 781]. We describe here the modifications of the responses of Chlamydia-primed THP-1 cells to hydrocortisone (HCT) and methylprednisolone (MPL). HCT and MPL inhibited the production of the cytokines TNFalpha and IL-8. But HCT, which inhibited the respiratory burst in LPS-primed monocytes, paradoxically stimulated the phenomenon in Chlamydia-primed cells; MPL exerted no significant effect. Both glucocorticoids did not significantly modify the triggering effect of Chlamydia on NF-kappaB binding activity. On the expression of p22(phox), a protein subunit of the NADPH oxidase, HCT had an increasing and MPL a decreasing effect. Glucocorticoids thus had unexpected effects on the inflammatory response of Chlamydia-primed monocytes.

Anti-Inflammatory Agents↗

PubMed2004

Auditory processing in severely brain injured patients: differences between the minimally conscious state and the persistent vegetative state.

BACKGROUND: The minimally conscious state (MCS) is a recently defined clinical condition; it differs from the persistent vegetative state (PVS) by the presence of inconsistent, but clearly discernible, behavioral evidence of consciousness. OBJECTIVE: To study auditory processing among patients who are in an MCS, patients who are in a PVS, and healthy control subjects. METHODS: By means of (15)O-radiolabeled water-positron emission tomography, we measured changes in regional cerebral blood flow induced by auditory click stimuli in 5 patients in an MCS, 15 patients in a PVS, and 18 healthy controls. RESULTS: In both patients in an MCS and the healthy controls, auditory stimulation activated bilateral superior temporal gyri (Brodmann areas 41, 42, and 22). In patients in a PVS, the activation was restricted to Brodmann areas 41 and 42 bilaterally. We also showed that, compared with patients in a PVS, patients in an MCS demonstrated a stronger functional connectivity between the secondary auditory cortex and temporal and prefrontal association cortices. CONCLUSIONS: Although assumptions about the level of consciousness in severely brain injured patients are difficult to make, our findings suggest that the cerebral activity observed in patients in an MCS is more likely to lead to higher-order integrative processes, thought to be necessary for the gain of conscious auditory perception.

Acoustic Stimulation↗

PubMed2004

A european, multicenter, observational study to assess the value of gastric-to-end tidal PCO2 difference in predicting postoperative complications.

Automated online tonometry displays a rapid, semicontinuous measurement of gastric-to-endtidal carbon dioxide (Pr-etCO2) as an index of gastrointestinal perfusion during surgery. Its use to predict postoperative outcome has not been studied in general surgery patients. We, therefore, studied ASA physical status III-IV patients operated on for elective surgery under general anesthesia and a planned duration of >2 h in a European, multicenter study. As each center was equipped with only 1 tonometric monitor, a randomization was performed if more than one patient was eligible the same day. Patients not monitored with tonometry were assessed only for follow-up. The main outcome measure was the assessment of postoperative functional recovery delay (FRD) on day 8. Among the 290 patients studied, 34% had FRD associated with a longer hospital stay. The most common FRDs were gastrointestinal (45%), infection (39%), and respiratory (35%). In those monitored with tonometry (n = 179), maximum Pr-etCO2 proved to be the best predictor increasing the probability of FRD from 34% for all patients to 65% at a cut-off of 21 mm Hg (2.8kPa) (sensitivity 0.27, specificity 0.92, positive predictive value 64%, negative predictive value 70%). We conclude that intraoperative Pr-etCO2 measurement may be a useful prognostic index of postoperative morbidity.

Adult↗

PubMed2004

In vitro evaluation of glutathione peroxidase (GPx)-like activity and antioxidant properties of some Ebselen analogues.

Four analogues of Ebselen were synthesized and their glutathione peroxidase activity and antioxidant property evaluated and compared to Ebselen. Among the studied compounds, only diselenide [3] exhibited both glutathione peroxidase activity and radical-scavenging capability. Compounds [3] and [4] showed a strong inhibitory effect (53% and 43%, respectively) on the lipid peroxidation of linoleic acid compared to Ebselen and selenide derivatives ([1] and [2]) which were less active (28%, 26% and 18% inhibition, respectively). A concentration-dependent inhibitory effect was also found in the model of the formation of ABTS*+ radical cation: 65% and 89% inhibition for compound [3] at 10(-4) M and 5 x 10(-5) M, respectively, and 68% and 90% for compound [4], compared to 14% and 52% inhibition for Ebselen and the diselenides [1] and [2] (29%, 46% and 45%, 68%, respectively). By EPR spin trapping technique, the following inhibitory profile of the Ebselen analogues was observed towards the formation of thiyl radicals: Ebselen = [3]>[1]>[2]>[4]. Studies with compound [3] are in progress on oxidative stress cell models.

Antioxidants↗

PubMed2003

Increased cerebral functional connectivity underlying the antinociceptive effects of hypnosis.

The neural mechanisms underlying the antinociceptive effects of hypnosis are not well understood. Using positron emission tomography (PET), we recently showed that the activity in the anterior cingulate cortex (midcingulate area 24a') covaries with the hypnosis-induced reduction of affective and sensory responses to noxious thermal stimulation [Faymonville et al., Anesthesiology 92 (2000) 1257-1267]. In the present study, we assessed changes in cerebral functional connectivity related to the hypnotic state, compared to simple distraction and the resting state. Nineteen highly hypnotizable right-handed volunteers were studied using H2(15)O-PET. The experimental conditions were hot noxious or warm non-noxious stimulation of the right hand during resting state, mental imagery and hypnotic state. Using a psychophysiological interaction analysis, we identified brain areas that would respond to noxious stimulations under the modulatory action of the midcingulate cortex in, and only in, the hypnotic state. Hypnosis, compared to the resting state, reduced pain perception by 50%. Pain perception during rest and mental imagery was not significantly different. Analysis of PET data showed that the hypnotic state, compared to normal alertness (i.e., rest and mental imagery), significantly enhanced the functional modulation between midcingulate cortex and a large neural network encompassing bilateral insula, pregenual anterior cingulate cortex, pre-supplementary motor area, right prefrontal cortex and striatum, thalamus and brainstem. These findings point to a critical role for the midcingulate cortex in the modulation of a large cortical and subcortical network underlying its influence on sensory, affective, cognitive and behavioral aspects of nociception, in the specific context of hypnosis.

Adult↗

PubMed2002

Oxygen consumption and electron spin resonance studies of free radical production by alveolar cells exposed to anoxia: inhibiting effects of the antibiotic ceftazidime.

By EPR spectroscopy, we investigated free radical production by cultured human alveolar cells subjected to anoxia/re-oxygenation (A/R), and tested the effects of ceftazidime, an antibiotic previously demonstrated to possess antioxidant properties. Two A/R models were performed on type II pneumocytes (A549 cell line), either on cells attached to culture dishes (monolayer A/R model; 3.5 h of anoxia, 30 min of re-oxygenation) or after cell detachment (suspension A/R model; 1 h of anoxia, 10 min of re-oxygenation). Ceftazidime and selective inhibitors (SOD, Tiron, L-NMMA) were added before anoxia. Free radical production was assessed by the EPR spin trapping technique. Oxygen consumption was monitored, in parallel with EPR studies, in the suspension A/R model. The production of free radical species was demonstrated by the generation of PBN-radical adducts: (a(N) = 15.2 G) in the monolayer A/R model and a six-line EPR spectrum (a(N) = 15.7 G and a(H) = 2.7 G) in the suspension A/R model. A kinetic study performed by oximetry, in parallel with EPR spectroscopy, demonstrated marked alterations of the cell respiratory function and that the free radical production started during anoxia and increased during re-oxygenation. In the suspension A/R model, the amplitude of EPR spectra were decreased upon the addition of 200 U/ml SOD (37% inhibition), 0.1 mM Tiron (67% inhibition) and 1 mM L-NMMA (43% inhibition). Addition of 1 mM ceftazidime decreased the amplitude of EPR spectra (37% inhibition) in both A/R models. Complementary in vitro EPR studies demonstrated that CAZ scavenged the hydroxyl radical (produced by the Fenton reaction). The protective effect of ceftazidime in the cell model could thus be linked to its ability to scavenge superoxide anions, nitrogen-derived species and hydroxyl radicals.

Adenocarcinoma↗

PubMed2002

Brain function in the vegetative state.

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates for glucose are massively reduced in this condition. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This finding led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. We used voxel-based Statistical Parametric Mapping (SPM) approaches to characterize the functional neuroanatomy of the vegetative state. The most dysfunctional brain regions were bilateral frontal and parieto-temporal associative cortices. Despite the metabolic impairment, external stimulation still induced a significant neuronal activation (i.e., change in blood flow) in vegetative patients as shown by both auditory click stimuli and noxious somatosensory stimuli. However, this activation was limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we demonstrated that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction.

Cerebral Cortex↗

PubMedDate not supplied

Cerebral processing of auditory and noxious stimuli in severely brain injured patients: differences between VS and MCS.

We review cerebral processing of auditory and noxious stimuli in minimally conscious state (MCS) and vegetative state (VS) patients. In contrast with limited brain activation found in VS patients, MCS patients show activation similar to controls in response to auditory, emotional and noxious stimuli. Despite an apparent clinical similarity between MCS and VS patients, functional imaging data show striking differences in cortical segregation and integration between these two conditions. However, in the absence of a generally accepted neural correlate of consciousness as measured by functional neuroimaging, clinical assessment remains the gold standard for the evaluation and management of severely brain damaged patients.

Acoustic Stimulation↗