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C Delacourt

Publications and source records attributed to C Delacourt.

At least 73 records · Page 4Linked to original sources
PubMed1995

Tachykinins induce gelatinase production by guinea pig alveolar macrophages: involvement of NK2 receptors.

To determine whether tachykinins induce gelatinase production by guinea pig alveolar macrophages (AM), and to characterize the mechanism involved, we incubated AM with substance P (SP), neurokinin A (NKA), or the NH2-terminal fragment of SP, SP(1-7). The effects of increasing concentrations of selective NK1 and NK2 agonists on tachykinin-induced gelatinase production were also evaluated, as were the effects of a selective NK2 antagonist. Gelatinase activity in conditioned culture media (CCM) was assessed by zymography and quantified by image analysis. SP increased 92-kDa gelatinase activity in CCM of AM in a concentration-dependent manner, with a maximum increase at 10(-4) M. NKA, the NH2-terminal fragment of SP, and an NK1-selective agonist had no effect. In contrast, a selective NK2 agonist induced a concentration-dependent increase in gelatinase activity. The increase in this activity induced by SP and the selective NK2 agonist was inhibited by a selective NK2 antagonist. We conclude that SP induces gelatinase production by AM through NK2 receptor activation. The release of gelatinase may constitute one mechanism through which SP contributes to the epithelial lesions observed in bronchial hyperreactivity and asthma.

Animals↗
PubMed1995

Increased 92 kD gelatinase activity from alveolar macrophages in newborn rats.

The functional immaturity of neonatal alveolar macrophages (AM) may contribute to the increased susceptibility of neonates to lung injury. Because the secretion of proteinases by neonatal AMs may be involved in normal postnatal lung development and in repair after lung injury, we evaluated the capacity of neonatal AMs to secrete 92 kD Type IV collagenase. AMs were obtained by bronchoalveolar lavage from newborn rats at different postnatal ages. Total gelatinase activity was measured by zymography in AM-conditioned media. Spontaneous secretion of gelatinase from AMs varied significantly with age, the highest levels being found immediately after birth. Stimulation of AMs by PMA induced a four- to fivefold greater increase in total gelatinase activity during the first 10 d of postnatal life compared with adulthood. Using [3H]gelatin as the substrate, we found high free gelatinase activity only within 24 h after birth; data obtained after exposing cells to natural surfactant suggested that surfactant may account in part for this increase in free gelatinase activity. No secretion of tissue inhibitor of metalloproteinases (TIMP) by AMs was detectable in newborns within 24 h after birth. We conclude that AMs from newborn rats are able to secrete more gelatinase than AMs from adults, and this enzyme production profile during the neonatal period may contribute to the fact that newborns with lung injury are at high risk for extracellular matrix degradation.

Animals↗
PubMed1995

Imbalance between 95 kDa type IV collagenase and tissue inhibitor of metalloproteinases in sputum of patients with cystic fibrosis.

A growing body of evidence suggests that neutrophil-derived proteinases play a major role in lung tissue damage in cystic fibrosis (CF). Most previous studies have focused on serine proteinases such as neutrophil elastase, providing no information on the extent to which metalloproteinases participate in proteolytic processes in CF. To address this issue, we evaluated the contribution of one of the major neutrophil metalloproteinases, i.e., 95 kDa gelatinase (type IV collagenase), to the total gelatinolytic activity measured in sputum specimens from 27 patients with CF. Compared with asthmatic children (n = 9), CF patients had a 6.7 times greater level of total gelatinase activity in sputum revealed by zymography. The 95 kDa gelatinase was increased 3.7-fold in the CF subjects (2,441 +/- 411 [SEM] arbitrary units [AU] x 10(6) per ml of sputum versus 665 +/- 201 in asthmatics) and the 88-kDa active form 23.2-fold (2,272 +/- 372 AU x 10(6) per ml of sputum versus 98 +/- 43, respectively). Using radiolabeled 3H-gelatin as the substrate, we demonstrated uninhibited gelatinolytic activity in all CF patients; this activity was significantly correlated to disease severity as assessed by pulmonary function tests. Western blotting using anti-tissue inhibitor of metalloproteinase (anti-TIMP) and anti-95/88-kDa gelatinase antibodies demonstrated a more than 10-fold excess of 95/88 kDa gelatinase over TIMP. Bacterial proteinases from Pseudomonas aeruginosa were shown to contribute little to the gelatinolytic activity measured in sputum supernatants from patients with CF, although culture supernatants from various P. aeruginosa strains expressed gelatinolytic activity in vitro. Finally, lung damage, as assessed by increased type IV collagen degradation products in sputum, was significantly correlated to concentrations of active 88 kDa gelatinase. These data argue for a significant role of 95/88 kDa gelatinase in airway damage in CF.

Adolescent↗
PubMed1995

Neutrophil-derived long-lived oxidants in cystic fibrosis sputum.

We evaluated long-lived oxidant potential in the sputum of patients with cystic fibrosis (CF) by quantitating the methionine-inhibitable, long-lived oxidant fraction of sputum, referred to as the chloramines. Taurine, the preferred amino acid substrate for chloramine formation, and myeloperoxidase (MPO), the chlorinated oxidant-generating enzyme, were also quantitated. As compared with the sputum of asthmatic subjects, the sputum of CF patients contained high concentrations of chloramines along with high levels of taurine and active MPO. A negative correlation between chloramine and taurine was found in the sputum of CF patients. No correlation was found between the density of Pseudomonas aeruginosa and the level of chloramines, taurine, or MPO. In contrast, respiratory parameters (%FEV or %FVC) and a nutritional index correlated positively with chloramine levels, whereas negative correlations were observed with taurine and MPO. In addition, the effect of antibiotic therapy, which significantly increased chloramine and decreased taurine levels, supported a beneficial effect of chloramines on overall clinical status. Our findings support a dual role of long-lived oxidants at the site of airway inflammation in CF, one component of which is their ability to mediate oxidative stress and the other a beneficial effect that may be partly explained by their inhibitory effect on antiprotease defense systems.

Adolescent↗
PubMed1994

Ability of new lung function tests to assess methacholine-induced airway obstruction in infants.

We assessed the ability of innovative lung function tests to detect bronchial obstruction induced by methacholine bronchial challenge. Fifty-five recurrently wheezy infants (mean age 16 +/- 5.2 months) free of respiratory symptoms underwent baseline lung function tests. Forty-two completed the methacholine challenge. Maximal flow at functional residual capacity (VmaxFRC) was obtained using the squeeze technique; compliance and resistance of the respiratory system (Crs, Rrs) was measured with the passive expiatory flow volume technique; tidal volume breathing patterns were analyzed from recordings of respiratory rate (RR), tidal volume (VT), and inspiratory time divided by total cycle of duration (Ti/Ttot). Expiratory tidal flow volume (V/VT) curves were described with multiple indices such as the ratio of expiratory time necessary to reach peak tidal expiratory flow (Fpet) to expiratory time (Tme/Te). Transcutaneous oxygen tension (PtCO2) was measured as an indicator of response to methacholine challenge. Of 42 infants 41 responded to methacholine by a change > or = 2 standard deviations from baseline values. The mean SD unit changes were 9.8 in PtCO2, 3.7 for VmaxFRC, 2.8 for Crs, 2.09 for Rrs, 3.1 for RR, 1.6 for Ti/Ttot, 2.2 for Tme/Te 3.9 for PFVt. We conclude that these noninvasive lung function tests, especially VmaxFRC and Fpet, can be used to detect minor or moderate airway obstruction. Further studies are needed to determine the value of the tests in assessing bronchial disease and effects of its treatment.

Airway Obstruction↗
PubMed1994

Sensitization to inhalant allergens in wheezing infants is predictive of the development of infantile asthma.

Early recognition of infantile asthma in wheezing infants is a major problem for physicians. We investigated whether detection of early sensitization to inhalant allergens would be useful to identify those wheezing infants who are likely to develop asthma. A total of 67 infants (aged 1-25 months) hospitalized for a wheezing episode were initially tested for reactivity to inhalant allergens by both skin prick test and in vitro measurement of specific IgE antibodies (Phadiatop). Thirty-seven of the infants were already considered to have infantile asthma, and 30 presented only their first or second wheezing episode when included in the study. All infants were followed for a mean period of 18 months. Seventeen (25%) infants, including seven infants initially not asthmatic, had positive prick test to Dermatophagoides pteronyssinus or to cat fur. All of these children were diagnosed as suffering from infantile asthma at the end of the follow-up. Thus, skin test positivity to inhalant allergens was significantly associated with the diagnosis of infantile asthma (P < 0.05) and could be considered to be predictive of the development of infantile asthma (P < 0.03). In contrast, Phadiatop was less sensitive than skin prick tests, and only five children had positive in vitro test results, suggesting that specific IgE may primarily bind to tissue mast cells before being detectable in serum. We concluded that sensitization to inhalant allergens may distinguish wheezing infants who develop asthma from those who do not, and that skin testing may assist the early diagnosis of asthma in wheezing infants.

Aging↗
PubMed1994

Matrix metalloproteinase and elastase activities in LPS-induced acute lung injury in guinea pigs.

Matrix metalloproteinases (MMPs) and elastase are proteolytic enzymes specifically directed against extracellular matrix (ECM) components. They are secreted by inflammatory cells and may consequently contribute to the lesions of the ECM observed during acute pulmonary edema. We therefore evaluated the MMP and elastase activities, which are secreted by cultured alveolar macrophages (AMACs) and polymorphonuclear neutrophils (PMNs) and present in the bronchoalveolar lavage (BAL) fluid in a guinea pig model of acute lung injury induced by intratracheal instillation of lipopolysaccharide (LPS). The control group was given 0.9% NaCl. 24 h after instillation, a BAL was performed, the BAL fluid was separated from the cells by centrifugation, and AMACs and PMNs were separately cultured for 24 h. In BAL fluid from LPS-treated guinea pigs, we found 1) an increase in free gelatinase activity, tested on [3H]gelatin (0.7 +/- 0.2 micrograms.200 microliters BAL fluid-1.48 h-1 vs. 0.2 +/- 0.1 in controls, P < 0.05), and 2) increased total gelatinase activities, as assessed by zymography. The molecular masses of the major gelatinase species found in BAL fluid by zymography were 92 and 68 kDa. The 92-kDa gelatinase was secreted by both AMACs and PMNs, as demonstrated by zymography of their respective culture media. When tested on [3H]elastin, the elastase activity of BAL fluid of LPS-treated animals exhibited no increase, but when tested on a synthetic peptidic substrate [N-succinyl-(L-alanine)3-p-nitro anilide (SLAPN)], increased elastase-like activity was observed (from 17 +/- 4 nmol of SLAPN.200 microliters BAL fluid-1.24 h-1 in control group to 34 +/- 8 in LPS group, P < 0.05). This increase was attributable to the activity of a metalloendopeptidase that was inhibited by the metal chelator EDTA but not by the specific tissue inhibitor of MMPs.

Animals↗
PubMed1994

[Value of ipratropium bromide in asthma crisis in children].

Ipratropium bromide is a synthetic derivative of atropine with little absorption when used in inhalation, and therefore little secondary effects. The authors review its pharmacological properties and therapeutic efficacy in the treatment of asthma in children. Combined nebulized inhalation of ipratropium bromide and beta 2 sympathomimetic results in a more efficient and more sustained bronchodilatation than beta 2 sympathicomimetic alone in the treatment of acute asthma in children. Ipratropium bromide should be usefully introduced in the therapeutic scheme of acute asthma in children. Further studies will be necessary in order to determine its efficacy and tolerance in infants.

Adolescent↗
PubMed1993

Computed tomography with normal chest radiograph in tuberculous infection.

Children with primary tuberculosis infection without disease must be identified and treated preventively to avoid an increase in the incidence of tuberculosis in children. However, the recognition of infected cases without disease is often difficult. In particular, minimal active disease may be present in many cases but unrecognised on chest radiography. Computed tomography was therefore performed in 15 children with tuberculous infection and a normal chest radiograph to measure the size of their mediastinal lymph nodes. Ten control children without tuberculosis were also evaluated. When compared with controls it was found that nine of 15 (60%) infected children had enlarged lymph nodes. Adenopathies were more frequent in infected children less than 4 years old than in those over 8 years old. The demonstration of unrecognised active disease in many infected children raises the question of the adequate treatment for these children. It is proposed that a two drug regimen would be more appropriate than isoniazid alone in these cases.

Adolescent↗
PubMed1993

Value of ELISA using antigen 60 for the diagnosis of tuberculosis in children.

We evaluated the possible value of enzyme-linked immunosorbent assay (ELISA) using antigen 60 (A60) for improved diagnosis of tuberculosis in children. Results obtained in 31 children with active tuberculosis and in 16 patients with tuberculous infection without disease were compared with the results of 198 control subjects with no mycobacterial disease. In control children, anti-A60 IgG increased with age and the optical density (OD) in ELISA assays rose from .079 +/- .053 (OD +/- SD) in children younger than 5 years old to 0.146 +/- 0.082 OD in children older than 5 years. In control subjects younger than 2 years old, IgG OD values were significantly higher in BCG-vaccinated children than in nonvaccinated children. At a chosen specificity of 98 percent, a positive serodiagnosis was observed in 68 percent of children with clinically active tuberculosis. In these children with active disease, smears were positive in only 26 percent of cases and mycobacterial cultures yielded the organism in 45 percent of cases. None of the infected children without disease had high IgG OD values. IgM measurements were also evaluated. Mean values from control and diseased children overlapped, leading to a low sensitivity (19 percent) in children with clinically tuberculosis active. We conclude that anti-A60 IgG measurement is a rapid and low-cost technique that enhances the diagnosis of clinically active tuberculosis in children and may distinguish recent infection without disease from infection with disease.

Adolescent↗
PubMed1993

Bronchiectasis in a child after acrolein inhalation.

Acrolein is an unsaturated aldehyde produced by combustion of many organic compounds. Massive exposure may lead to severe pulmonary disease and possibly death. We report a case of intoxication in a 2-year-old boy; an 18-month follow-up showed development of obstructive bronchiolar disease with diffuse bronchiectasis.

Accidents, Home↗
PubMed1993

[Vaccinations of children allergic to eggs with vaccine prepared with egg].

BACKGROUND: The mumps, influenza, yellow fever and measles vaccines are grown in chick-embryos. Because allergic reactions to these vaccines have occasionally been reported in children who have suffered anaphylaxis from egg ingestion, it has been claimed that these children should not receive such vaccines. PATIENTS AND METHODS: 17 egg-allergic children aged 1 year 1 month to 7 years 10 months (mean 2 years 4 months) were studied. All had developed an allergic reaction less than one hour after egg ingestion. Allergy was confirmed by skin testing (prick skin test) and detection of IgE antibodies to egg (RAST). RESULTS: Seven children were immunized normally by their general practitioner, who was not aware of their allergy; 8 children having negative prick skin and intradermal tests with the vaccine were also immunized normally while 2 children who had positive intradermal test with the vaccine received divided doses following a protocol established for this study. None of these 17 egg-allergic children developed local and/or general reactions. Reintroduction of egg (yolk then white) was tested on the day of immunization in 4 children: only one developed facial edema. CONCLUSION: This protocol permits these vaccines to be safely given to egg-allergic children.

Child↗
PubMed1993

[Toxicity of fire smoke. Apropos of 2 pediatric cases].

BACKGROUND: Smoke inhalation is one of the main cause of respiratory problems in fire-related accidents. CASE REPORTS: Case 1. A girl, aged 11 months, was found in her apartment 15 minutes after the start of accidental fire. She was in a stage I coma with cyanosis and covered with soot. She was placed on oxygen and given hydroxocobalamin. Aggravation of respiratory problems led to mechanical ventilation. Tracheobronchoscopy showed deposits of soots with moderate burnt lesions. Intubation was discontinued 12 hours later, but the child remained oxygen-dependent, with persistent tracheobronchitis, despite steroid therapy for 2 weeks. Case 2. Another girl, aged 4 1/2 years, was found in the same room as the preceding patient. She was also covered with soot, and in a coma (Glascow score = 11). She was intubated, placed on mechanical ventilation, and given hydroxocobalamin. Tracheobronchoscopy revealed similar changes to those seen in the preceding patient. Despite repeated tracheobronchial washings and steroid therapy, respiratory problems persisted with thoracic distension and pneumothorax. Mechanical ventilation was discontinued 16 days later but at 5 1/2 years, this child still has dyspnea and has developed bronchiectasis. CONCLUSION: Bronchopulmonary changes can be a severe complication of smoke inhalation during fires, and require early mechanical ventilation and repeated tracheobronchoscopy.

Carbon Monoxide Poisoning↗
PubMed1993

Serum bactericidal test as a prognostic indicator in acute pulmonary exacerbations of cystic fibrosis.

The serum bactericidal test has been used for many years for optimal assessment of the efficacy of antibiotic therapy in patients with infective endocarditis and other bacterial infections. Its capacity to predict the bacteriological outcome of acute pulmonary exacerbations in patients with cystic fibrosis was evaluated. A total of 54 courses of intravenous antibiotic therapy were analyzed in 22 patients, whose ages ranged from 4 months to 24 years (mean age: 10 years). The serum bactericidal activity of blood samples, taken at expected peak and trough antibiotic levels on day 4 of therapy, were determined against the potentially pathogenic strains isolated in sputum at the time of admission. For 104 isolates (64 Pseudomonas aeruginosa, 28 Staphylococcus aureus, and 12 Haemophilus influenzae strains), the peak and trough bactericidal titers were compared to bacteriological outcome. Bacteriological success was defined as a decrease of 2 log10 units or more in the bacterial density in sputum between days 0 and 7 of therapy. At peak antibiotic levels, serum bactericidal titers of 1:128 or more were 96% (all isolates) and 89% (P aeruginosa isolates), predictive of cure, whereas serum bactericidal titers of less than 1:16 were 100% predictive of failure for all infecting bacteria. In patients aged less than 18 years, the best peak titer for predicting success was 1:64, with a predictive value of 96% for titers of 1:64 or greater. The peak titer that best predicted success in patients aged 18 years or more was 1:128, with a predictive value of only 83% for titers of 1:128 or greater.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

[The asthmatic child].

Asthma is the most frequent chronic pediatric disease. Management is based on assessment of severity and should normalize lifestyle as well as pulmonary function. Mild asthma is treated with intermittent beta-2-agonists. Moderate asthma should receive non-steroids prophylactic anti-inflammatory drugs. Immunotherapy should be considered. Severe asthma requires inhaled steroids. At each stage inhaled medications should be preferred. Therefore inhalation delivery system must be adapted for children of different ages and degree of dyspnea. The importance of environment control is well recognized. Establishing a partnership with the child and its family and with the medical staff and with the child's school is always necessary.

Asthma↗
PubMed1992

Clinical trials on pediatric lower-respiratory-tract infection: results and comments with cefetamet pivoxil.

A total of 30 pediatric patients suffering from lower-respiratory-tract infections were admitted to a three-arm, open, randomized study comparing two different doses of cefetamet pivoxil (either 10 or 20 mg/kg b.i.d.; groups A and B, respectively) with the standard cefaclor treatment (10 mg/kg t.i.d.; group C) for 7-12 days. The 30 cases were randomly assigned to the three treatment arms which were comparable with regard to demographics as well as to diagnosis on admission and concomitant medication. The children ranged from 1.08 to 12 years in age, and comprised 18 males and 12 females, with a weight range of 11-42 kg. As is to be expected in these patients, bacteriology was mostly not assessable. The overall clinical outcome was cure in 9, 8 and 9 cases, respectively, and improvement in 1, 2 and 0 cases, respectively. In the cefaclor group 1 patient failed to respond. Signs and symptoms of disease improved significantly in the three treatment groups; there were no intergroup differences. Vital signs (morning and evening temperature and pulse rate) improved in parallel. Radiological results had improved by the end of treatment in 9/10 patients in group A, in 10/10 patients in group B, and in 9/10 evaluable patients in group C. Mild to moderate nausea or vomiting were each reported in 1 patient in group A. Platelet increase was reported as a mild adverse event in 2 patients in each of the cefetamet pivoxil groups and in 4 patients given cefaclor.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗