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Biomedical subjects

C Guillot

Publications and source records attributed to C Guillot.

At least 19 recordsLinked to original sources
PubMed2006

Factors controlling BTEX and chlorinated solvents plume length under natural attenuation conditions.

Natural attenuation is presently used at numerous sites where groundwater is contaminated. In order to simulate this attenuation, reactive transport models are often used but they are quite complex and depend on both physical and chemical conditions in the aquifer. As complex numerical models cannot be used to study all possible cases, we develop here analytical solutions to draw general conclusions. Our strategy, called MIKSS (Mixed Instantaneous and Kinetics Superposition Sequence), allows the calculation of the concentrations of all reacting substances in a plume. It is an extension of the superimposition principle that is able to treat the case of joint kinetics and instantaneous reactions. The basic equations have been extended to treat different reactions that occur in the plume core and at its fringe. At first we consider one organic substance degraded under all oxidising conditions (toluene for instance). For this problem the size of the plume depends on the reduced source width and on the ratio of the organic substance concentration to the sum of the electron acceptors' concentrations. For several BTEX substances having different degradation behaviour the formulation is similar, but leads to quite different plume lengths for each substance. Contrary to the case of one substance, the plumes can be quite long and may not satisfy the target risk level. For chlorinated solvents we developed a specific approach to take under consideration all reactions and particularly the competition for hydrogen. A formula is given to assess the size of the plume core, i.e. the zone with highly reducing conditions. The factors influencing the core length are the same as for BTEX (source width, dispersivity, organic carbon content). The size of the TCE plume is calculated from the plume core length and the kinetic constant of TCE degradation. Using assumptions of degradation constants for DCE and VC it is also possible to calculate the longitudinal concentration profile of these substances. The degradation of moderately substituted solvents under oxic conditions reduces the size of their plumes but under these conditions TCE becomes the major threat. Among the conditions studied in this paper, very few chlorinated solvents sites can lead to a negligible risk at an acceptable distance from the source.

Aerobiosis↗
PubMed2006

Scaling exponents for fracture surfaces in homogeneous glass and glassy ceramics.

We investigate the scaling properties of postmortem fracture surfaces in silica glass and glassy ceramics. In both cases, the 2D height-height correlation function is found to obey Family-Viseck scaling properties, but with two sets of critical exponents, in particular, a roughness exponent zeta approximately 0.75 in homogeneous glass and zeta approximately 0.4 in glassy ceramics. The ranges of length scales over which these two scalings are observed are shown to be below and above the size of the process zone, respectively. A model derived from linear elastic fracture mechanics in the quasistatic approximation succeeds to reproduce the scaling exponents observed in glassy ceramics. The critical exponents observed in homogeneous glass are conjectured to reflect the damage screening occurring for length scales below the size of the process zone.

Journal Article↗
PubMed2006

Same efficacies of ipratropium and salbutamol in reversing methacholine-induced bronchoconstriction.

Efficacy of salbutamol (S) was compared to that of ipratropium (I) or to their association, after methacholine challenge testing (MCT). MCT was performed in 4 groups of 10 patients suspected to suffer from asthma; mean changes in FEV1, maximal midexpiratory flow rate (MMFR), and airway resistance (Raw) were the same in all groups. After MCT, the group 1 patients inhaled S and then I, 10 min later; both drugs were given in the reverse order to the group 2 patients. The group 3 patients inhaled a mixture of both drugs just after MCT; the group 4 patients were not given any bronchodilator till the 20th min after MCT, when they inhaled S. Short-term (10 min) bronchodilator effects of S, I or S + I on spirometric variables were of the same magnitude and Raw returned to its baseline value. Further improvement (10-20 min) in FEV1 was mainly due to spontaneous recovery, whereas further increase in MMFR was due also to bronchodilator actions of drugs. It is concluded that ipratropium could be proposed as an alternative bronchodilator to salbutamol after MCT.

Adult↗
PubMed2004

Increased diaphragmatic strength and tolerance to fatigue after bilateral lung transplantation: an electromyographic study.

We evaluated the diaphragmatic function of seven patients with severe chronic respiratory failure before and after a bilateral lung transplantation (BLT), with follow-up at one year of pulmonary function tests, maximal inspiratory mouth pressure (MIP) and surface diaphragmatic electromyogram (Edi). The patients were asked to sustain target inspiratory pressures at -15, -30, and -50 cmH(2)O. We measured the endurance time (Tlim) to sustain inspiratory efforts and the power spectrum density function of Edi at each inspiratory maneuver. The Edi power spectra was analysed in terms of median frequency (MF), total power (TP) and energies in high-and low-frequency bands (EL and EH). Before BLT, a defect of the diaphragmatic function was evident: MIP was 62+/-7% of the predicted value and the Tlim measured at each inspiratory effort was very short ( 13+/-1 s, 10+/-1 s and 8+/-1 s at pressures of -15, -30, and -50 cmH(2)O, respectively). One month after BLT, the Tlim began to increase at all target inspiratory pressures and at 6 months MIP recovered to normal values. One month after BLT, there was a significant decrease in TP measured at the beginning of each inspiratory efforts and also an increase in the concomitant MF value. BLT markedly accentuated the maximal variations of TP, MF and low-frequency Edi energy. Some hypotheses are raised to explain this dramatic improvement in diaphragmatic function after BLT.

Adolescent↗
PubMed2003

Electrostatic charge on spacer devices and salbutamol response in young children.

Electrostatic charge on plastic spacer devices may affect the efficacy of inhaled drugs, but its consequences have never been evaluated in asthmatic children with airflow limitation. At the end of a positive metacholine challenge, 64 children (51.3+/-12.9 months, 32 boys, specific airway resistance (SRaw) 257.1+/-56.7% and forced expiratory volume in 1s (FEV(1)) 64.2+/-17.9% of the predicted value) inhaled one puff of hydrofluoroalkane-134a (HFA-134a) salbutamol (Ventoline((R))), and 15min later two other puffs (total dose of 300 microgram), delivered through either a new static Babyhaler((R)) (n=21), a detergent-coated, reduced static, Babyhaler((R)) (n=20), or a metal NES-Spacer((R)) (n=23) equipped with facemask. SRaw and FEV(1) were measured after each treatment and compared between groups by a Kruskal-Wallis test. The first 100 microgram salbutamol induced a 151.7+/-43.9% decrease in SRaw and a 19.9+/-10.6% increase in FEV(1). Additional 200 microgram salbutamol allowed a supplementary decrease of 35.1+/-25.7% in SRaw and increase of 12.1+/-11.8% in FEV(1), without significant difference between the spacer devices. Electrostatic charge on spacer devices does not affect bronchodilation with HFA-134a salbutamol in metacholine-challenged pre-school children. This could be in part explained by the use of supramaximal doses of salbutamol.

Administration, Inhalation↗
PubMed2003

Glass breaks like metal, but at the nanometer scale.

We report in situ atomic force microscopy experiments which reveal the presence of nanoscale damage cavities ahead of a stress-corrosion crack tip in glass. Their presence might explain the departure from linear elasticity observed in the vicinity of a crack tip in glass. Such a ductile fracture mechanism, widely observed in the case of metallic materials at the micrometer scale, might be also at the origin of the striking similarity of the morphologies of fracture surfaces of glass and metallic alloys at different length scales.

Journal Article↗
PubMed2003

Assessment of T lymphocyte cytokine production in induced sputum from asthmatics: a flow cytometry study.

BACKGROUND: Asthma results from a bronchial inflammation in which Th2 lymphocytes play a pivotal role, as shown in invasive bronchial biopsies and broncho-alveolar lavages. Induced sputum (IS) is a non-invasive method of recovery of bronchial cells, which can be repeated in the same patients. However, lymphocyte activation has not been studied in IS to date, because of the low number of T cells recovered. Herein we took advantage of flow cytometry, a method suitable for the study of small cell populations, to assess T cell cytokine production in IS. OBJECTIVES: (1) To assess induced sputum T cell cytokine production by flow cytometry in asthmatic subjects and controls. (2) To compare the T cell cytokine production between symptomatic and non-symptomatic asthmatics. METHODS: Thirteen asthmatics and 19 controls were included. Sputum was induced by a hypertonic saline. Sputum cells were stimulated and intracellular IL-13 and IFN-gamma were detected in T cells by flow cytometry. RESULTS: Stimulation induced an increase of IL-13 and IFN-gamma production by T cells. This increase was higher in asthmatics. IL-13-producing T cells were increased in asthmatics after stimulation. In symptomatic asthma, IFN-gamma-producing T cells were in higher proportion than in controlled asthma. CONCLUSION: IS T cell cytokine production indicates a basic Th2 bias in asthma, accompanied during symptoms by a Th1-like activation. These results open the field for longitudinal studies of the variation of T cell activation in asthma.

Adult↗
PubMed2002

Genetic engineering in allotransplantation of vascularized organs.

Transplantation offers a unique opportunity for gene transfer into allografts before grafting. After organ retrieval, the cold ischemic period renders organs available for manipulation and gene transfer. Local expression of protective or immunomodulatory molecules within the graft environment offers a better local bioavailability of bioreagents and potentially less systemic side effects. Protection against ischemia-reperfusion injury, acute and/or chronic rejection without significant side effects would be a major breakthrough in transplant research. However, protocols of transfection adapted to the transplant setting and control of gene expression must be clearly evaluated before going to clinical trials. The first part of this review deals with gene transfer techniques into the allograft, emphasizing particular transplant conditions that are encountered and that must be respected when designing protocols for gene transfer experiments. The second part deals with specific therapeutic strategies to protect and prolong allograft survival.

Adenoviridae↗
PubMed2001

Lethal hepatitis after gene transfer of IL-4 in the liver is independent of immune responses and dependent on apoptosis of hepatocytes: a rodent model of IL-4-induced hepatitis.

The putative role of IL-4 in human and animal models of hepatitis has not yet been directly determined. We now report that direct expression of IL-4 in the liver of rats or mice using recombinant adenoviruses coding for rat or mouse IL-4 (AdrIL-4 and AdmIL-4, respectively) results in a lethal, dose-dependent hepatitis. The hepatitis induced by IL-4 was characterized by hepatocyte apoptosis and a massive monocyte/macrophage infiltrate. IL-4-induced hepatitis was independent of T cell-mediated immune responses. Hepatitis occurred even after gene transfer of IL-4 into nude rats, CD8-depleted rats, cyclosporine A-treated rats, or recombinase-activating gene 2(-/-) immunodeficient mice. Peripheral depletion of leukocytes using high doses of cyclophosphamide, and/or the specific depletion of liver macrophages with liposome-encapsulated dichloromethylene diphosphonate in rats did not block lethal IL-4-induced hepatitis. Direct transduction of hepatocytes with adenoviruses was not essential, since injection of AdrIL-4 into the hind limb induced an identical hepatitis. Finally, primary rat hepatocytes in culture also showed apoptosis when cultured in the presence of rIL-4. IL-4-dependent hepatitis was associated with increases in the intrahepatic levels of IFN-gamma, TNF-alpha, and Fas ligand. Administration of AdmIL-4 to IFN-gamma, TNF-alpha receptor type I, or TNF-alpha receptor type II knockout mice also resulted in lethal hepatitis, whereas a moderate protection was observed in Fas-deficient lpr mice. IL-4-dependent hepatocyte apoptosis could be abolished by treatment with caspase inhibitory peptides. Our results thus demonstrate that IL-4 causes hepatocyte apoptosis, which is only partially dependent on the activation of Apo-1-Fas signaling and is largely independent of any immune cells in the liver.

Acute Disease↗
PubMed2000

Tolerance to cardiac allografts via local and systemic mechanisms after adenovirus-mediated CTLA4Ig expression.

Blockade of the CD28/B7 T cell costimulatory pathway prolongs allograft survival and induces tolerance in some animal models. We analyzed the efficacy of a CTLA4Ig-expressing adenovirus in preventing cardiac allorejection in rats, the mechanisms underlying heart transplant acceptance, and whether the effects of CTLA4Ig were restricted to the graft microenvironment or were systemic. CTLA4Ig gene transfer into the myocardium allowed indefinite graft survival (>100 days vs 9 +/- 1 days for controls) in 90% of cases, whereas CTLA4Ig protein injected systemically only prolonged cardiac allograft survival (by up to 22 days). CTLA4Ig could be detected in the graft and in the serum for at least 1 year after gene transfer. CTLA4Ig gene transfer induced local intragraft immunomodulation at day 5 after transplantation, as shown by decreased expression of the IL-2R and MHC II Ags; decreased levels of mRNA encoding for IFN-gamma, inducible NO synthase, and TGF-beta; and inhibited proliferative responses of graft-infiltrating cells. Systemic immune responses were also down-modulated, as shown by the suppression of Ab production against donor alloantigens and cognate Ags, up to at least 120 days after gene transfer. Alloantigenic and mitogenic proliferative responses of graft-infiltrating cells and total splenocytes were inhibited and were not reversed by IL-2. In contrast, lymph node cells and T cells purified from splenocytes showed normal proliferation. Recipients of long-term grafts treated with adenovirus coding for CTLA4Ig showed organ and donor-specific tolerance. These data show that expression of CTLA4Ig was high and long lasting after adenovirus-mediated gene transfer. This expression resulted in down-modulation of responses against cognate Ags, efficient suppression of local and systemic allograft immune responses, and ultimate induction of donor-specific tolerance.

Abatacept↗
PubMed2000

Changes in maximal performance of inspiratory and skeletal muscles during and after the 7.1-MPa Hydra 10 record human dive.

During the 7.1-MPa hydrogen-helium-oxygen record human dive, we tested the hypothesis that the increased ambient pressure would alter the maximal muscle performance, specifically that breathing dense gas would lead to fatigue of the respiratory muscle. A group of hand muscles (adductor pollicis, AP) and the inspiratory muscles (IM) were studied in three professional divers. Maximal voluntary contractions (MVC) of AP and maximal inspiratory pressure (P(i(max))) generated by IM were measured prior to the dive, during compression and decompression, and then 1 and 2 months after the dive. The decrease in MVC (-22%) was significant at 3.1 MPa, i.e. at the beginning of the introduction of hydrogen into the breathing mixture, whereas P(i(max)) fell progressively during the dive and decompression (maximal DeltaP(i(max)) = -55%), a significant reduction still being measured 1 month after the dive. The altered IM function was attributed to the consequences of long-term ventilatory loading, a condition associated with breathing a dense gas. The transient decrease in MVC of the skeletal muscle would indicate a possible effect of the hyperbaric environment, possibly the high partial pressure of hydrogen, on neuromuscular drive.

Diving↗
PubMed2000

Gene therapy in transplantation in the year 2000: moving towards clinical applications?

Transplantation faces several major obstacles that could be overcome by expression of immunomodulatory proteins through application of gene therapy techniques. Gene therapy strategies to prolong graft survival involve gene transfer of immunosuppressive or graft-protecting molecules. Very promising results have been obtained in small animal experimental models with inhibitors of co-stimulatory signals on T cells, immunosuppressive cytokines, donor major histocompatibility antigens and regulators of cell apoptosis or oxidative stress. The application of gene therapy techniques to transplantation offers a great experimental and therapeutic potential. Local production of immunosuppressive molecules may increase their therapeutic efficiency and reduce their systemic effects. When compared with other clinical situations, gene therapy in transplantation offers several potential advantages. Gene transfer into the graft can be performed ex vivo, during the transit between the donor and the recipient, thus avoiding many of the hurdles encountered with in vivo gene transfer. Furthermore, the difficulties associated with immune responses to the gene transfer vectors and transient gene expression may be easier to overcome when gene therapy protocols are applied to transplantation than when applied to other clinical situations. The next century should witness a rapid increase in the application of gene therapy techniques to large animal pre-clinical models of transplantation and later to clinical trials. Gene Therapy (2000) 7, 14-19.

Apoptosis↗
PubMed2000

Interleukin-10 produced by recombinant adenovirus prolongs survival of cardiac allografts in rats.

Interleukin-10 (IL-10) and interleukin-4 (IL-4), two Th2-derived cytokines, are molecules with anti-inflammatory and immunodeviating properties whose direct expression in allografts may prolong graft survival. Recombinant adenoviruses represent efficient vectors for gene transfer in quiescent cells in vivo. Adenoviral vectors encoding rat IL-10 (AdIL-10), rat IL-4 (AdIL-4) or beta-galactosidase (AdlacZ) or without transgene (Addl324) were injected directly into rat hearts at the time of transplantation in order to test their potential to prolong heart allograft survival. Expression of vectorized sequences was confirmed in heart biopsies, and kinetic analysis of beta-galactosidase showed transient expression. Cardiac allograft survival was significantly prolonged after administration of 10(9) p.f.u. of AdIL-10 (16.6 +/- 3.2 days, P < 0.05), but not AdIL-4 (9.8 +/- 1.6 days), compared with Addl324-treated (9.3 +/- 3.3 days) or untreated groups (7.8 +/- 1.5 days). Immunohistochemical analysis of allografts after gene transfer of IL-10 showed that leukocyte infiltration was quantitatively equivalent to that seen in control groups but with a strong tendency towards lower levels of CD8+ cells. Importantly, adenovirus-derived IL-10 modified the functional status of leukocytes by inducing a significant decrease in IFN-gamma production but significantly increased transforming-growth factor beta 1 (TGF-beta 1) expression within the grafts compared with those treated with Addl324. These results show that expression of IL-10 by rat hearts after gene transfer mediated by an adenoviral vector decreases allogeneic immune responses and allows prolongation of allograft survival.

Adenoviridae↗
PubMed2000

Value of bronchial challenge in scuba diving candidates.

Bronchial challenges were effected with carbachol in 76 subjects who were candidates for a scuba diving group. Bronchial reactivity was assessed through airway resistance and forced expiratory volume in 1 sec (FEV1) measurements. Medical interrogation had revealed symptoms of recent (RA) or ancient (AA) asthma, or allergic rhinitis (AL). Nearly half of the subjects (47%) presented bronchial hyperresponsiveness (BHR), which was much more frequent in the RA group, but whose strength did not depend on clinical presentation. Prevalence of BHR was fairly high (36%) in the AL group. BHR constituted a contraindication to scuba diving because it may promote pulmonary barotrauma.

Adult↗
PubMed1999

M-wave changes after high- and low-frequency electrically induced fatigue in different muscles.

The mechanisms of fatigue-induced changes in evoked compound muscle action potential (M-waves) are not well documented. In rats, isolated fast-glycolytic (tibialis anterior, or TA) and slow-oxidative muscles (soleus, or SOL) were stimulated repetitively at a low (10-Hz) or high (80-Hz) rate. Decreased amplitude and prolonged duration of M-waves were only significant after high-frequency fatigue in TA and SOL muscles; that is, in the conditions in which an influx of calcium was measured. On the other hand, maximal force failure and maximal lactic acid increase in the bath medium occurred in TA muscle after high- and low-frequency fatigue trials. Postfatigue increase in potassium concentration occurred in all circumstances. Thus, M-wave alterations depend mainly on the stimulation paradigm and not on the muscle type, and cannot be used as a marker of changes in intracellular potassium or lactate ions. This amplifies understanding of the significance of M-wave changes in human exercise protocols.

Animals↗
PubMed1999

Bronchial challenge with carbachol in 3-6-year-old children: body plethysmography assessments.

Several studies of airway responsiveness in young children (3-6 years old) have been reported, but few have attempted measurements of airway resistance by body plethysmography. Therefore, we decided to study nonspecific bronchial responsiveness following cumulative doses of inhaled carbachol in 44 children with clinical asthma (CA group), 44 children with chronic cough (CC group), 38 children with wheezy bronchitis in the first 2 years of life (WB group), and 40 controls. Specific airway resistance (sRaw) was measured in a body plethysmograph, and specific airway conductance (sGaw=1/sRaw) was calculated. Two parameters were used to assess individual bronchial responses: 1) PD100 (the dose of carbachol which induced a 100% increase in sRaw), and 2) bronchial reactivity (BR), i.e., the slope of the log-dose sGaw response to carbachol. Significant differences were observed in PD100 and BR between the control group and the three groups of young patients (P < 0.001). Moreover, PD100 of the CA group was significantly lower than in the CC group (83.1 +/- 7.8 microg vs. 108.0 +/- 10.2 microg, respectively, P < 0.05), but was similar to the WB group PD100 (94.4 +/- 8.5 microg). BR in the CA group was significantly higher than in both the CC and WB groups (0.127 +/- 0.009 cm H2O-L.sec(-1) x log microg(-1) vs. 0.073 +/- 0.006 cm H2O(-1) x sec(-1) x log microg(-1) and 0.082 +/- 0.006 cm H2O(-1) x sec(-1) x log microg(-1), respectively, P < 0.001). Repeatability and coefficients of variation were always acceptable. Continuous SaO2 monitoring in some children of the CA group demonstrated the safety of the method, which is proposed as a technique in future studies.

Asthma↗