Biomedical subjects

D Girard

Publications and source records attributed to D Girard.

At least 19 recordsLinked to original sources

PubMed2006

[Optoelectronic gait analysis after metatarsophalangeal arthrodesis of the hallux: fifteen cases].

PURPOSE OF THE STUDY: Degeneration of the metatarsophalangeal joint of the hallux is a frequent secondary lesion of the first ray subsequent to hallux valgus. Different surgical techniques have been proposed for cure, including metatarsophalangeal arthrodesis. Joint fusion relieves pain but sacrifices joint motion. The purpose of this work was to assess changes observed in gait after metatarsophalangeal arthrodesis of the hallux using a three-dimensional optoelectronic system. MATERIAL AND METHODS: Gait analysis was performed with a Vicon 3D system with five cameras and two AMTI force platforms in twelve patients who had undergone metatarsophalangeal arthrodesis more than six months earlier. The kinetic and kinematic curves and ground reaction forces were analyzed. Changes in the gait cycle and any compensations observed in the talocrural and interphalangeal joints were noted in the three dimensions. Wilcoxon test for paired series was applied for the statistical analysis. RESULTS: The general gait parameters and kinetic and kinematic values were not modified (excepting a non-significant decline in maximal dorsiflexion of the ankle joint). There was a significant decrease in propulsion force in the anteroposterior and vertical planes, with significantly later heal lift-off and systematic displacement of ground reaction forces anterior to the metatarsophalangeal joint on the arthrodesis side. Reflectors positioned on the distal extremity of the hallux demonstrated that the essential part of compensation occurred at the level of the interphalangeal joint. DISCUSSION: Gait analysis after tibiotalar arthrodesis has been widely reported in the literature. The consequence of joint fusion on the rear foot and/or the torsion couple have also been studied. However, to our knowledge, there has been only one report using a different methodology devoted to metatarsophalaneal arthrodesis of the hallux. In this study, only step length and interphalangeal moment as well as ankle force were found to be decreased. Function of the interphalangeal joint was not assessed. The Vicon system enabled an adapted study of gait after metatarsophalangeal arthrodesis. This method offers several perspectives: study of the effect of the position of the arthrodesis in the sagittal plane on gait, changes over time in interphalangeal joint motion, or consequences of fusion on walking up and down stairs. CONCLUSION: Metatarsophalangeal arthrodesis of the hallux does not modify general gait parameters nor the kinetic and kinematic values. Compensation is achieved via the interphalangeal joint.

Aged↗

PubMed2005

Enhanced efficacy of single-dose versus multi-dose azithromycin regimens in preclinical infection models.

OBJECTIVES: As a result of the prolonged half-life and unique pharmacokinetic and pharmacodynamic (PK-PD) characteristics of azithromycin, shorter dosing regimens are being evaluated for the treatment of community-acquired infections. To provide further support for a shorter dosing regimen, the efficacy of azithromycin was determined in preclinical infection models comparing single- versus multi-dose regimens. METHODS: The efficacy of single versus multi-dose regimens of azithromycin was compared in mouse pneumonia, acute peritonitis, and neutropenic thigh infection models and in a gerbil model of Haemophilus influenzae acute otitis media. Azithromycin was administered as a single oral dose on the first treatment day, or as two divided doses over 2 treatment days, or as three divided doses over 3 treatment days. The pharmacokinetics of azithromycin was profiled following single and multi-dose regimens with the single dose data fit to an Emax model to characterize the PK-PD of azithromycin. RESULTS: In the mouse efficacy models, administration of single-dose azithromycin produced superior rates of survival and bacterial clearance compared with the same total dose divided over 2 or 3 days. In the gerbil model, a single dose sterilized the middle ear and more rapidly cleared H. influenzae. The pharmacokinetic evaluation confirmed similar total exposure (AUC) in serum and pulmonary tissue for the three regimens. Correlation of PK-PD parameters and antimicrobial efficacy confirmed a concentration-dependent and dosing-independent relationship for azithromycin. CONCLUSIONS: These data are consistent with data reported from clinical studies and indicate that a single-dose regimen would be at least as effective as the same dose administered over several days.

Animals↗

PubMed2005

Interleukin-15 increases neutrophil adhesion onto human respiratory epithelial A549 cells and attracts neutrophils in vivo.

Interleukin-15 (IL-15) is a neutrophil agonist that plays a role in inflammatory disorders, including a variety of pulmonary diseases. Adhesion of neutrophils onto pulmonary cells is a major event leading to development of inflammation. Recently, elevated levels of IL-15 have been associated with different pulmonary diseases. There is no clear evidence that IL-15 modulates cell surface expression of adhesion molecules in neutrophils, or that IL-15 is involved in neutrophil adhesion onto pulmonary cells. Also, it is not clear if IL-15 induces a neutrophilic inflammation in vivo. This study was aimed at elucidation of these issues. Neutrophils were treated with IL-15 and cell surface expression of CD11a, CD11b, CD11c and CD18 was monitored by flow cytometry. The human respiratory epithelial A549 cell line was used as a substrate for the neutrophil adhesion assay and cell surface expression of CD50, CD54 and CD106 was monitored in IL-15-induced A549 cells. The murine air pouch model was used for investigating potential neutrophilic inflammation induced by IL-15 in vivo. IL-15 significantly increased neutrophil cell surface expression of CD11b and CD18 and up-regulated A549 cell surface expression of CD54. Moreover, A549 cells were found to express IL-15R components and adhesion of neutrophils onto A549 cells was increased when neutrophils or A549 cells were treated with IL-15. Finally, IL-15 induced neutrophilic inflammation in vivo and concentrations of IL-6 and CXCL2/MIP-2 were increased in IL-15-induced pouches. IL-15 might participate in inflammatory pulmonary diseases by attracting neutrophils, modulating cell surface expression molecules and increasing neutrophil adhesion onto pulmonary cells.

Animals↗

PubMed2004

Anti-inflammatory effect of Viscum album agglutinin-I (VAA-I): induction of apoptosis in activated neutrophils and inhibition of lipopolysaccharide-induced neutrophilic inflammation in vivo.

Viscum album agglutinin-I (VAA-I) is a plant lectin which possesses antitumoral properties. This lectin is also known for its immunostimulatory effects when used at low concentrations (1-100 ng/ml). We have demonstrated recently that VAA-I is a potent inducer of human neutrophil apoptosis in vitro when used at higher concentrations. The role of VAA-I on activated neutrophils has not so far been investigated and its potential proinflammatory properties in vivo are poorly documented. Herein, we demonstrated that VAA-I (1000 ng/ml) induces apoptosis in lipopolysaccharide (LPS)-treated human neutrophils in vitro as well as in murine neutrophils isolated from lipopolysaccharide (LPS)-induced neutrophil influx. Using this model, we found that administration of VAA-I (100 or 1000 ng/ml) did not induce an inflammatory response. However, when used at 1 or 10 ng/ml, VAA-I was found to significantly induce a transitory inflammatory response, based on an increased leucocyte infiltration (>98% neutrophils). Also, we found that VAA-I inhibits LPS-induced neutrophil influx when administered simultaneously with LPS. In such conditions, some characteristic apoptotic neutrophils were observed in the pouch. Unlike LPS, which increased the production of some cytokines, VAA-I (1 or 10 ng/ml) did not increase the production of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1Ra, IL-1alpha, IL-beta, IL-8, IL-10 or IL-12 (p70) in human neutrophils. We conclude that VAA-I possesses the ability to induce apoptosis of preactivated neutrophils at a concentration that does not induce a proinflammatory response. Moreover, we conclude that VAA-I can inhibit a LPS-induced proinflammatory response in vivo. These data may provide new clinical perspectives in future mistletoe therapy and favour its potential utilization based on anti-inflammatory activity that at first appears contradictory with its use as immunostimulant.

Animals↗

PubMed2002

Dieldrin induces human neutrophil superoxide production via protein kinases C and tyrosine kinases.

We have recently found that dieldrin is a potent human neutrophil agonist in vitro and induces neutrophilic inflammation in vivo. Among the responses observed in vitro, dieldrin was found to induce superoxide (O2-) production by a yet unknown mechanism. In the present study, dieldrin- and phorbol 12-myristate 13-acetate (PMA)-induced O2- responses were compared. For this purpose, cells were preincubated with a panel of signal transduction inhibitors including genistein, H-7, HA-1077, pertussis toxin, staurosporine, calphostin C, SB203580, PD098059, and wortmannin. Dieldrin-induced O2- response was significantly reduced with treatment with genistein, H-7, HA-1077, staurosporine, and calphostin C, whereas PMA-induced response was significantly reduced by treatment with H-7, HA-1077, and staurosporine. This indicates that dieldrin mediates its effect via protein kinases C (PKCs) and tyrosine kinases. Involvement of tyrosine kinases in dieldrin-induced human neutrophils was further demonstrated by an increase in tyrosine phosphorylated protein level expression. Finally, we found that treatment with the mitochondrial stabilizer bongkrekic acid and with the inhibitor of vesicular transport brefeldin A did not reverse dieldrin-induced O2- response.

Cell Culture Techniques↗

PubMed2001

Activation of human neutrophils by technical toxaphene.

Toxaphene is a persistent organic pollutant (POP) known to be composed of numerous congeners. Toxaphene technical mixture applied as a pesticide consists of over 800 congeners. Among these, T(2) and T(12) are the two environmentally prevalent forms found in humans. Although toxaphene is known to exert some toxic effects, including potential proinflammatory properties, little is known concerning its action on cells of the human immune system, especially neutrophils. In the present study, we found that toxaphene was not necrotic for human neutrophils incubated for up to 24 h with concentrations ranging from 0.1 to 50 microg/ml. Toxaphene was found to induce neutrophil superoxide production (O(-)(2)) in a concentration-dependent manner. The potency and the kinetics of toxaphene-induced O(-)(2) by neutrophils were found to be similar to that of the classical neutrophil agonists phorbol 12-myristate 13-acetate (PMA). Furthermore, the use of various transduction signal inhibitors (genistein, pertussis toxin, staurosporine, H-7, and HA-1077), suggests that, as for PMA, toxaphene mediates its effect primarily via PKCs and, to a lesser extend, via tyrosine kinases. In this respect, staurosporine, H-7, and genistein were found to inhibit toxaphene- and PMA-induced O(-)(2) production by 52, 72, and 31% and by 63, 62, and 23%, respectively. Toxaphene was also found to significantly enhance neutrophil phagocytosis of opsonized sheep red blood cells and to induce neutrophil apoptosis. The induction of neutrophil apoptosis was paralleled with a decrease in CD16 expression. T(2) and T(12), the two prevalent congeners found in humans, were also found to significantly increase the O(-)(2) production in neutrophils at a concentration of 5 microg/ml. We conclude that neutrophils are important targets for toxaphene, as this POP can activate O(-)(2) production by a PKC- and tyrosine kinase-dependent mechanism, induce phagocytosis, and accelerate the apoptotic rate. This is the first study that focuses on toxaphene/human neutrophil interactions.

Apoptosis↗

PubMed2001

Modulation of interleukin-15-induced human neutrophil responses by the plant lectin Viscum album agglutinin-I.

The plant lectin Viscum album agglutinin-I (VAA-I) and the interleukin-15 (IL-15) cytokine are two molecules with potential therapeutic properties known to modulate neutrophil functions when used separately. This study was conducted in order to better understand the mode of action of VAA-I and to elucidate how VAA-I could modulate IL-15-induced neutrophil responses. We found that VAA-I cannot induce phosphorylation events in human neutrophils. However, it enhances phagocytosis by itself without altering IL-15-induced phagocytosis. VAA-I was found to reverse the ability of IL-15 to delay neutrophil apoptosis and this was correlated with an inhibition of IL-15-induced de novo protein synthesis. In addition, we also found that IL-15 cannot reverse or attenuate the caspase-induced gelsolin fragmentation observed during apoptosis as assessed by immunoblotting. We conclude that VAA-I can be used to modulate some, but not all, IL-15-induced neutrophil responses and that it acts independent of phosphorylation events.

Adjuvants, Immunologic↗

PubMed2001

Seroprevalence of human herpes virus 8 antibody in populations at high or low risk of transfusion, graft, or sexual transmission of viruses.

BACKGROUND: The routes of transmission of human herpes virus 8 (HHV-8) remain unclear. In particular, HHV-8 transmission by blood components and organ transplantation is still debated and raises public health issues. The objective of this study was to determine the prevalence of anti-HHV-8 in selected populations of persons or patients with or without risk factors for the transmission of viral infections, in order to determine the routes of HHV-8 transmission. STUDY DESIGN AND METHODS: A total of 1431 persons or patients at low or high risk of sexually, blood-, or graft-transmitted viral infections were tested by means of a standardized immunofluorescence serologic assay detecting anti-HHV-8. RESULTS: The persons or patients could be classified into three distinct groups according to anti-HHV-8 prevalence: a low prevalence group (0.0% to 5.0%), including healthy blood donors, healthy pregnant women, multiply transfused patients with thalassemia major, and IV drug users; an intermediate prevalence group (5.0% to 20.0%), including organ donors, kidney transplant recipients, and multiply transfused patients with sickle cell disease; a high prevalence group (>20.0%), including HIV-negative persons at high risk of sexually-transmitted viral infections, and HIV-infected homosexual men and heterosexuals. CONCLUSION: The sexual route appears to be the main route of HHV-8 transmission; bloodborne transmission of HHV-8, if it exists, is rare. In contrast, organ transplantation recipients might be exposed to HHV-8 transmission by the transplanted organ, which raises the issue of systematic screening of organ donors.

Adult↗

PubMed2001

Activation of human neutrophils by chlordane: induction of superoxide production and phagocytosis but not chemotaxis or apoptosis.

We have recently reported that human neutrophils are important targets of different xenobiotics, including chemicals of environmental concern. In the present study, we found that chlordane was not toxic for human neutrophils incubated for up to 24 h with concentrations ranging from 0.1 to 50 microg/ml. Chlordane was found to induce neutrophil superoxide production (O2-) in a concentration-dependent fashion and its potency to induce this response was found to be similar to phorbol 12-myristate 13-acetate (PMA), a classical neutrophil agonist. The use of different transduction signal inhibitors (genistein, pertussis toxin, staurosporine, and calphostin C) indicates that, as for PMA, chlordane induces O2- production via protein kinase C (PKC). In this respect, staurosporine and calphostin C were found to inhibit chlordane- and PMA-induced O2- production by 65% and 72%, and by 83% and 85%, respectively. Chlordane was also found to significantly enhance neutrophil phagocytosis of opsonized sheep red blood cells (SRBCs). Despite these effects, chlordane did not alter neutrophil apoptosis as assessed by cytology (Diff-Quick staining) and by flow cytometry (CD-16 expression). In addition, chlordane did not alter neutrophil chemotaxis (48-well Boyden chamber). Cells were, however, responsive as they were activated by the well-characterized interleukin (IL)-8 chemokine. We conclude that chlordane can activate O2- production by a PKC-dependent mechanism and induce phagocytosis without altering chemotaxis and apoptosis. Chlordane must be added to a growing list of environmental contaminants that share some pro-inflammatory properties.

Apoptosis↗

PubMed2001

Activation of human neutrophils in vitro and dieldrin-induced neutrophilic inflammation in vivo.

Many chemicals of environmental concern are known to alter the immune system and are considered toxic molecules because they affect immune cell functions. Inflammation related to environmental chemical exposure, however, is poorly documented, except that from air pollutants. In this study, we found that the organochlorine insecticide dieldrin could not alter the ability of human neutrophils to phagocytose opsonized sheep red blood cells at nonnecrotic concentrations (0.1, 1, 10, and 50 microM). However, dieldrin was found to increase human neutrophil superoxide production, RNA synthesis, and proinflammatory cytokine interleukin-8 production. The normal apoptotic rate of neutrophils evaluated by both cytology and flow cytometry (CD-16 staining) was not altered by dieldrin treatments, and this was correlated with its inability to inhibit spreading of neutrophils onto glass. Using the murine air pouch model, we found that dieldrin induces a neutrophilic inflammation. Taken together, these results demonstrated that dieldrin is a proinflammatory contaminant. To our knowledge, this is the first report establishing that dieldrin is a contaminant exhibiting proinflammatory properties. In addition, it is the first time that the murine air pouch model has been successfully used to confirm that a chemical of environmental concern can induce an inflammatory response in vivo.

Animals↗

PubMed2000

Activation of human neutrophils by the air pollutant sodium sulfite (Na(2)SO(3)): comparison with immature promyelocytic HL-60 and DMSO-differentiated HL-60 cells reveals that Na(2)SO(3) is a neutrophil but not a HL-60 cell agonist.

Sulfite exposure can induce inflammatory responses characterized by an influx of neutrophils into the airways leading to lung malfunctions. Studies focusing on sodium sulfite (Na(2)SO(3))/neutrophil interactions have shown that this chemical possesses proinflammatory properties based on its ability to induce a respiratory burst. Information regarding how this chemical could alter other neutrophil responses/functions as well as its role on immature promyelocytic cells is currently lacking in the literature. In this study, we report that Na(2)SO(3) can induce tyrosine phosphorylation events in human neutrophils but not in both HL-60 and HL-60 + DMSO. As a positive control, GM-CSF was found to induce tyrosine phosphorylation of a particular protein of 120-130 kDa in both HL-60 and HL-60 + DMSO cells testifying that these cells were responsive. In addition, we report that Na(2)SO(3) does not alter neutrophil phagocytosis and that this chemical increases the release of the proinflammatory cytokine IL-8 but not TNF-alpha. Paradoxically, we found that Na(2)SO(3) acts as a potent inhibitor of de novo neutrophil protein synthesis in a concentration-dependent fashion (0.1, 1, or 10 mM) as assessed by SDS-PAGE from metabolically [(35)S]-labeled cells. In contrast to mature neutrophils, we found that Na(2)SO(3) does not modulate de novo protein synthesis in HL-60 cells treated with low concentrations (0. 1 or 1 mM) and that this pollutant was toxic at 10 mM as judged by a drastic decrease of total protein content stained with Coomassie blue. We conclude that Na(2)SO(3) can activate human neutrophils and that its proinflammatory potential is further supported by its ability to increase IL-8 production. In addition, our results clearly indicate that HL-60 and HL-60 + DMSO respond differently than mature human neutrophils to the inflammatory pollutant Na(2)SO(3). Extrapolation of data obtained with HL-60 (and/or HL-60 + DMSO) to neutrophils should be taken with caution. Our data obtained with Na(2)SO(3) are an example.

Air Pollutants↗

PubMed2000

Activity of a sub-cutaneously administered novel mixed micellar formulation of argatroban in rat and rabbit models of venous thrombosis.

We studied the antithrombotic activity of a mixed micellar formulation containing 14 mg/ml argatroban administered by the subcutaneous (s.c.) route in rat and rabbit models of venous thrombosis. The effects on bleeding time in the rat tail transection bleeding time test were also studied. In a tissue factor-dependent arterio-venous shunt model, argatroban treatment led to dose-dependent reduction in thrombus weight with an estimated ID50 of 1.8 mg/kg s.c. In the same model, heparin had an estimated ID50 of 179 IU/kg. The antithrombotic activity of argatroban was accompanied by increases in the thrombin and ecarin clotting times but not the aPTT, whereas heparin increased the thrombin time and aPTT but not the ecarin clotting times. Argatroban also inhibited thrombus formation in a rabbit model of thromboplastin + stasis induced thrombosis in the rabbit jugular vein with an estimated ID50 of 1 mg/kg s.c. When tested in the rat tail transection bleeding time test, the mixed micellar formulation of argatroban caused significant increases in the bleeding time as from 8 mg/kg s.c., while heparin significantly increased the bleeding time at 800 U/kg. Mixed micellar argatroban appears to have a superior safety margin to heparin in terms of antithrombotic efficacy and bleeding risk. Thus, a mixed micellar formulation of argatroban, which markedly enhances its solubility, could be useful as a potential antithrombotic agent for subcutaneous administration.

Animals↗

PubMed2000

Activation of human neutrophils by the plant lectin Viscum album agglutinin-I: modulation of de novo protein synthesis and evidence that caspases are involved in induction of apoptosis.

The plant lectin Viscum album agglutinin-I (VAA-I) was recently found to modulate protein synthesis and to induce apoptosis in various cells of immune origin. We found that VAA-I induces de novo protein synthesis of metabolically 35S-labeled human neutrophils when used at low concentrations (< 100 ng/mL) but acts as an inhibitor at higher concentrations. Using both flow cytometry (FITC-Annexin-V/PI labeling) and cytology (Diff-Quick staining) approaches, we found that VAA-I could not modulate neutrophil apoptosis at low concentrations but could induce it in >98% of cells at 500 and 1000 ng/mL. VAA-I was also found to reverse the delaying effect of GM-CSF on neutrophil apoptosis and to inhibit GM-CSF-induced de novo protein synthesis. In contrast to GM-CSF, VAA-I does not induce tyrosine phosphorylation by itself and does not alter the GM-CSF-induced response. Among the inhibitors used, genistein, pertussis toxin, staurosporine, H7, Calphostin C, manoalide, BpB, quinacrine HA-1077, and z-VAD-FMK, only the latter (inhibitor of caspases-1, -3, -4, and -7) was found to inhibit VAA-I-induced neutrophil apoptosis as the percentage of apoptotic cells decrease from 98 +/- 1.3 to 54 +/- 3.2% (n=4). Furthermore, we confirm that caspases are involved in VAA-I-induced neutrophil apoptosis as we have observed the fragmentation of the cytoskeletal gelsolin protein that is known to be caspase-3-dependent. Such degradation was reversed by the z-VAD-FMK inhibitor. We conclude that induction of neutrophil apoptosis by VAA-I is a caspase-dependent mechanism that does not involve tyrosine phosphorylation events, G-proteins, PKCs, and PLA2. In addition, we conclude that at least caspase-3 is involved. Correlation between VAA-I-induced neutrophil apoptosis and VAA-I-induced inhibition of de novo protein synthesis is discussed.

Adjuvants, Immunologic↗

PubMed1999

Oxaliplatin-induced haemolytic anaemia.

A case of haemolytic anaemia after therapy with oxaliplatin, an anticancer chemotherapeutic agent, was investigated. Haemolytic anaemia has been associated with cisplatin and carboplatin, two related drugs, but not with oxaliplatin.

Adenocarcinoma↗

PubMed1999

Chronic rhinitis in workers at risk of reactive airways dysfunction syndrome due to exposure to chlorine.

BACKGROUND: To assess the frequency of chronic upper airways symptoms and to relate the presence of these symptoms to accidental exposure to chlorine and changes in lower airways symptoms, airway function, and bronchial responsiveness in a cohort of workers at risk of sporadic occupational exposure to high concentrations of chlorine. METHODS: Data were collected on symptom assessment, spirometry, and methacholine challenge tests from 211 workers seen twice at a 2 year interval (1992-4). RESULTS: The proportion of workers reporting chronic rhinitis was 46.9% in 1992 and 42.2% in 1994. Chronic rhinitis reported in 1994 was significantly associated with acute exposure to chlorine (self reports, p = 0.02; first aid reports, p = 0.001). In a multivariate logistic regression analysis the presence of reported accidents at the first aid unit (one accident, odds ratio (OR) 3.1, 95% confidence interval (95% CI) 1.3 to 7.5; two or more accidents, OR 6.2, 1.1 to 35.8) and of personal atopy (OR 5.5, 2.2 to 10.8) were significant predictors of chronic rhinitis in 1994. Chronic lower airways symptoms were more frequent in 1994 among workers reporting chronic rhinitis on both assessments than in others (p = 0.03) and changes in bronchial responsiveness were more pronounced in those with persistent rhinitis (p = 0.09). CONCLUSIONS: These results suggest that persistent nasal symptoms in workers at risk of reactive airways dysfunction syndrome could be a useful marker of lower respiratory tract abnormalities.

Accidents, Occupational↗

PubMed1999

Longitudinal assessment of airway caliber and responsiveness in workers exposed to chlorine.

This longitudinal study (1992-1994) was performed to determine the relation between accidental chlorine exposure and changes in lung function and airway responsiveness in 239 workers in a metal production plant. These workers had taken part in a cross-sectional survey in 1992. In both the initial and the follow-up surveys, history of exposure to chlorine ("puffs"), accidental chlorine inhalation reported to the first-aid unit (gassing incidents), and of chronic symptoms were documented; spirometry and methacholine challenge tests were performed. At follow-up, 211 workers (88.3%) were seen. In workers with 20 pack-years or more of cigarette smoking, the fall in FEV(1) was associated with having had a gassing incident during the follow-up period; the fall in FEV(1)/FVC (%) was predicted by the number of puffs causing mild symptoms between the two assessments. An increase in airway responsiveness (PC(20) decrease > 1.5-fold) was present in 19 workers; it was associated with accidents reported to the first-aid unit during the previous 2 yr (OR: 5.9, 95% CI: 1.1 to 32.3). These findings suggest: (1) an effect on airway function related to the estimated number of puffs with mild symptoms and gassing incidents, mostly among smokers; (2) a detectable increase in airway responsiveness associated with gassing incidents.

Accidents, Occupational↗

PubMed1998

Human neutrophils express the interleukin-15 receptor alpha chain (IL-15Ralpha) but not the IL-9Ralpha component.

The interleukin-15 receptor (IL-15R) is composed of at least three chains, namely gammac, IL-2Rbeta, and the recently identified IL-15Ralpha, while the IL-9R complex consists of gammac and a subunit designated IL-9Ralpha. Our previous work and that of others have shown that human neutrophils express gammac and IL-2Rbeta (two components shared with IL-2R) but not IL-2Ralpha and that IL-15 is a neutrophil agonist, whereas IL-2 is not. In this study, using flow cytometry with a specific anti-human IL-15Ralpha, we show for the first time that human neutrophils express surface IL-15Ralpha. Although we previously found that IL-15 is a neutrophil agonist, our present work shows that IL-15 does not trigger superoxide production nor cell spreading onto glass. In addition, we report that human neutrophils do not respond to IL-9 with respect to the functions/responses studied, namely, superoxide production, spreading onto glass, cell shape changes, phagocytosis, RNA synthesis, and apoptosis. Further, our results show that neutrophils do not express IL-9Ralpha as assessed by flow cytometry with a specific anti-human IL-9Ralpha antibody that stains the transfected cell line BW-h9R used as positive control. Finally, our results indicate that gammac expression was not modulated and remained stable for up to 24 h when neutrophils were stimulated with all currently known "gammac users," namely, IL-2, IL-4, IL-7, IL-9, and IL-15. We conclude that human neutrophils express all IL-15R components on their surface, including IL-15Ralpha, that IL-15 activates human neutrophils (as the IL-4 neutrophil agonist) by a mechanism which does not involve upregulation of gammac cell surface expression, and that IL-9 is not a neutrophil agonist as demonstrated by the inability to modulate the tested functions/responses that correlate with lack of the IL-9R component, namely, IL-9Ralpha.

Animals↗

PubMed1998

Estimation of the pulmonary capillary wedge pressure from transesophageal pulsed Doppler echocardiography of pulmonary venous flow: influence of the respiratory cycle during mechanical ventilation.

OBJECTIVE: Pulsed Doppler measurement of pulmonary venous flow (PVF) in the left superior pulmonary vein has been suggested as a noninvasive method to evaluate pulmonary capillary wedge pressure (PCWP). In previous studies, PVF was measured at end-expiration, and it is unknown to what extent PVF is affected by the respiratory cycle. It is hypothesized that phasic variations of PVF during mechanical ventilation may be used to estimate PCWP. DESIGN: Prospective clinical study. SETTING: Tertiary care university hospital. PARTICIPANTS: Thirty patients undergoing elective cardiac surgery. INTERVENTIONS: At multiple intervals during the surgery, the PVF was measured with transesophageal pulsed Doppler echocardiography, and measurements of PCWP and airway pressure were simultaneously obtained. MEASUREMENTS AND RESULTS: Components of PVF evaluated were the systolic (X), diastolic (Y), and atrial (Z) waves with their velocity-time integrals (VTI). The systolic fraction (SF = VTI X/[VTI X + VTI Y]) and respiratory variations of each component of PVF were determined and compared with PCWP. There was a greater respiratory variation of the X wave (X expiratory-X inspiratory/X expiratory) in patients with PCWP < 18 mmHg than in patients with PCWP > or = 18 mmHg (0.19 +/- 0.19 v 0.14 +/- 0.13, respectively, p < 0.01). PVF components measured at end-expiration that related best with PCWP were the X/Y peak velocities (r = -0.53), VTI X/VTI Y ratio (r = -0.42), and the SF (r = -0.49). When measured during end-inspiration, the relation of the X/Y ratio, VTI X/VTI Y, and SF with the PCWP were r = -0.54, r = -0.41, and r = -0.50, respectively. CONCLUSIONS: It has been documented that PVF velocity is influenced by the respiratory cycle during mechanical ventilation in patients undergoing cardiac surgery, and the magnitude of this variation is influenced by PCWP. However, it is not actually possible to predict PCWP accurately using these findings. Further studies are needed in which preload is varied acutely to confirm the usefulness of the results.

Adult↗