30 results on '"G. Tournier"'
Search Results
2. Pulmonary sarcoidosis in children: a follow-up study.
- Author
-
Baculard A, Blanc N, Boulé M, Fauroux B, Chadelat K, Boccon-Gibod L, Tournier G, and Clement A
- Subjects
- Adolescent, Blood Gas Analysis, Bronchoalveolar Lavage, Cell Count, Child, Child, Preschool, Disease Progression, Female, Follow-Up Studies, Glucocorticoids administration & dosage, Humans, Lung Compliance, Male, Prednisone administration & dosage, Pulmonary Gas Exchange, Radiography, Thoracic, Sarcoidosis, Pulmonary physiopathology, Treatment Outcome, Vital Capacity, Glucocorticoids therapeutic use, Prednisone therapeutic use, Sarcoidosis, Pulmonary drug therapy
- Abstract
Progression of pulmonary sarcoidosis in children remains poorly documented. The aim of this work was to gather follow-up information on pulmonary outcomes in children with sarcoidosis and to obtain data of relevance to a discussion of the optimal length and regimen of glucocorticoid therapy. In the present study, the authors experience of pulmonary sarcoidosis in 21 children referred to the paediatric pulmonary department over a 10-yr period is reported with a documented follow-up of at least 4 yr. Evaluation of the disease during the follow-up included analysis of clinical manifestations, chest radiographs, pulmonary function tests with measurements of the vital capacity (VC), dynamic lung compliance (CL,dyn), lung transfer for CO (TL,CO), and arterial blood gases, as well as bronchoalveolar lavage (BAL) with determination of total and differential cell counts. After initial evaluation the decision was a careful observation of four children without therapy. Corticosteroid treatment was initiated in 17 children. Analysis of results indicated that after 6-12 months of treatment most clinical manifestations of the disease and chest radiograph abnormalities disappeared, and beneficial effects on VC and TL,CO were apparent. After 18 months of steroids no benefit on pulmonary function tests could be noticed, with mainly persistence of alterations of CL,dyn. Results of BAL studies documented the presence of an alveolitis with increased lymphocyte populations throughout the follow-up. Relapses were observed in four children during tapering of prednisone; they were not reported after discontinuation of steroid therapy. Taken together data obtained in the presented population can lead to the following suggestions for the management of pulmonary sarcoidosis in children. BAL should be performed at the initial evaluation to document alveolitis; however, nothing seems to be gained from repeating this investigation during follow-up in the absence of specific reasons. Once the decision to initiate glucocorticoid therapy is made, 18 months may be a reasonable treatment duration. Discontinuation of therapy can be decided even if the pulmonary function tests remain abnormal, but the child should then be carefully monitored for a relapse.
- Published
- 2001
- Full Text
- View/download PDF
3. Genotype analysis and phenotypic manifestations of children with intermediate sweat chloride test results.
- Author
-
Desmarquest P, Feldmann D, Tamalat A, Boule M, Fauroux B, Tournier G, and Clement A
- Subjects
- Adolescent, Child, Child, Preschool, Cystic Fibrosis complications, Cystic Fibrosis diagnosis, Female, Genotype, Heterozygote, Homozygote, Humans, Infant, Male, Mutation, Phenotype, Respiratory Tract Infections complications, Chlorides analysis, Cystic Fibrosis genetics, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Sweat chemistry
- Abstract
Study Objectives: Cystic fibrosis (CF) is one of the most common inherited diseases among whites. Since the cloning of the CF transmembrane conductance regulator (CFTR) gene, a number of studies have focused on associations between the genotype and phenotype in CF. This had led to the progressive identification of new groups of patients, including those who have mild lung disease and those who have normal sweat chloride values (< 60 mEq/L). The aim of the present work was to provide information on the genotype and the phenotypic characteristics of children with intermediate-range sweat chloride test results., Patients and Results: We focused on children referred to the pulmonary department for various types of pulmonary disease and who had several sweat chloride test results with median values in the range of 40 to 60 mEq/L. Twenty-four patients over a 10-year period were enrolled (mean age, 4.8 years). Respiratory manifestations at initial evaluation included recurrent bronchitis, wheezing, chronic cough, and pneumonia. The duration of the follow-up ranged from 0.5 to 10.5 years. Sputum cultures revealed the presence of Haemophilus influenzae (10 children), Staphylococcus aureus (4 children), and Pseudomonas aeruginosa (3 children). Pancreatic insufficiency was found in two patients. Analysis of the entire coding sequence allowed identification of 16 known mutations in CFTR gene. Fifteen chromosomes (31.2%) carried a mutation in CFTR gene and one allele carried two mutations. Three patients were homozygous or double heterozygous (DeltaF508/DeltaF508, DeltaF508/3849 + 10 kb C-->T, S1235R/G551D). The 5-thymidine allele was identified in four children., Conclusion: These results indicate an higher frequency of CFTR gene mutations in patients with borderline sweat chloride test results, compared to data reported in the general population. They lead to the recommendations for complete pulmonary and GI investigations in this group of patients, as well as assiduous care and medical follow-up.
- Published
- 2000
- Full Text
- View/download PDF
4. Distinct sputum cytokine profiles in cystic fibrosis and other chronic inflammatory airway disease.
- Author
-
Osika E, Cavaillon JM, Chadelat K, Boule M, Fitting C, Tournier G, and Clement A
- Subjects
- Adolescent, Adult, Bronchiectasis diagnosis, Child, Cystic Fibrosis diagnosis, Female, Humans, Inflammation Mediators metabolism, Interleukin-6 metabolism, Male, Reference Values, Bronchiectasis immunology, Cystic Fibrosis immunology, Cytokines metabolism, Sputum immunology
- Abstract
The dominant role of inflammation in airways disease progression in cystic fibrosis (CF) is now well established and, based on recent findings, the possibility of an inappropriate inflammatory response in the lung of patients with CF has emerged. In order to characterize this response, the aim of the present work was to evaluate the levels of a number of pro- and anti-inflammatory cytokines in the sputum of CF children and to compare these levels to those observed in the sputum from non-CF children with diffuse bronchiectasis (DB). Three groups of patients were investigated: a group of 25 CF children (mean age: 12.2 yrs), a group of 10 non-CF children with DB (mean age 11.5 yrs), and a group of five healthy young adults (mean age 24 yrs). Elevated concentrations of pro-inflammatory cytokines, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-8 were found in children with CF and in non-CF children with DB, with significantly higher concentrations of IL-1beta in CF children. Analysis of the natural anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) and type II TNF soluble receptor (sTNFRII) concentrations showed distinct patterns, with elevated levels of both inhibitors in CF patients, whereas only sTNFRII was found to be increased in non-CF children with DB. IL-10 data indicated low concentrations in the CF group. In all CF children, the concentrations of IL-6 in the airways were extremely low, independent of the clinical, bacteriological or functional status. By contrast, significantly increased IL-6 levels were found in non-CF children with DB. These results document distinct cytokine profiles in cystic fibrosis patients and noncystic fibrosis patients. They also suggest that impairment of interleukin-6 expression may represent an important component of the excessive inflammatory response observed in cystic fibrosis.
- Published
- 1999
- Full Text
- View/download PDF
5. Chronic interstitial lung disease in children: response to high-dose intravenous methylprednisolone pulses.
- Author
-
Desmarquest P, Tamalet A, Fauroux B, Boule M, Boccon-Gibod L, Tournier G, and Clement A
- Subjects
- Adolescent, Biopsy, Bronchoalveolar Lavage Fluid cytology, Bronchoalveolar Lavage Fluid microbiology, Bronchoscopy, Child, Preschool, Chronic Disease, Dose-Response Relationship, Drug, Drug Evaluation, Female, Humans, Infant, Injections, Intravenous, Lung pathology, Lung Diseases, Interstitial blood, Lung Diseases, Interstitial diagnosis, Male, Prospective Studies, Treatment Outcome, Anti-Inflammatory Agents administration & dosage, Lung Diseases, Interstitial drug therapy, Methylprednisolone administration & dosage
- Abstract
The prognosis for children with chronic interstitial lung disease is poor and the mortality rate is high, especially in infants. This explains the many therapeutical protocols which have been proposed and investigated by several authors. In the present work, we evaluated the response of three infants with idiopathic pulmonary fibrosis to high-dose intravenous prednisolone pulses. The patients were referred to the department at the age of 4, 17, and 3 months, respectively. The diagnosis was confirmed by open lung biopsy and intravenous pulse methyl prednisolone therapy was started with the following protocol: 300 mg/m2 methylprednisolone daily for 3 days, repeated every 4 to 6 weeks. Because of the extreme severity of the respiratory distress at the time of diagnosis, the intravenous pulse treatments were initially complemented by oral prednisone. Clinical improvement was noticed within 6 months with progressive correction of hypoxemia. After follow-up for 3.5 to 4 years, with a total number of pulses of 37, 26, and 32, respectively, the children are symptom-free and do not require oxygen supplementation. During this period, no side effects and no adrenal insufficiency could be documented. Based on current knowledge of steroid action, it can be speculated that the response to intermittent high-dose intravenous methylprednisolone may explain the ability of this mode of hormone administration to maintain an adequate level of glucocorticoid receptor expression. More information and trials through multicenter collaborations are needed to assess therapeutical protocols of repeated high-dose intravenous steroid treatment.
- Published
- 1998
- Full Text
- View/download PDF
6. Multicenter, open-label study of recombinant human DNase in cystic fibrosis patients with moderate lung disease. DNase International Study Group.
- Author
-
Harms HK, Matouk E, Tournier G, von der Hardt H, Weller PH, Romano L, Heijerman HG, FitzGerald MX, Richard D, Strandvik B, Kolbe J, Kraemer R, and Michalsen H
- Subjects
- Administration, Inhalation, Adolescent, Adult, Child, Child, Preschool, Cystic Fibrosis physiopathology, Deoxyribonuclease I administration & dosage, Expectorants administration & dosage, Female, Humans, Male, Middle Aged, Prospective Studies, Recombinant Proteins administration & dosage, Recombinant Proteins therapeutic use, Respiratory Function Tests, Treatment Outcome, Cystic Fibrosis drug therapy, Deoxyribonuclease I therapeutic use, Expectorants therapeutic use
- Abstract
Cystic fibrosis is characterized by the accumulation of thick viscous purulent secretions. Recombinant human deoxyribonuclease I (rhDNase) breaks down extracellular DNA, which contributes to the increased viscosity of sputum. A multinational, open-label study was conducted in 974 cystic fibrosis patients with moderate lung disease [forced vital capacity (FVC) 40-70% of predicted values] to examine the safety and efficacy of aerosolized rhDNase, 2.5 mg, once daily over a period of at least 12 weeks. Patients were assessed under conditions reflecting routine clinical practice. During rhDNase therapy, at least one respiratory tract infection (RTI) requiring intravenous antibiotics was experienced by 29.5% of patients. Forced expiratory volume in 1 second (FEV1) and FVC were significantly improved from baseline by a mean of 10.5% and 7.2%, respectively. Voice alteration and pharyngitis were the most frequent rhDNase-related adverse events, but only 2% of all patients discontinued treatment due to adverse events. The results obtained were similar to a subanalysis of data from the first 3 months of a placebo-controlled U.S. study. The patients in the present study had a similar frequency of RTIs and improvement in pulmonary function, and reported fewer rhDNase-related and cystic fibrosis-related adverse events than patients in the U.S. study. We conclude that administration of rhDNase is safe, well tolerated, and effective under conditions reflecting routine clinical practice in patients with cystic fibrosis and moderate lung disease.
- Published
- 1998
- Full Text
- View/download PDF
7. Expression of insulin-like growth factors and their binding proteins by bronchoalveolar cells from children with and without interstitial lung disease.
- Author
-
Chadelat K, Boule M, Corroyer S, Fauroux B, Delaisi B, Tournier G, and Clement A
- Subjects
- Adolescent, Bronchoalveolar Lavage Fluid cytology, Cell Count, Child, Child, Preschool, Female, Humans, Insulin-Like Growth Factor Binding Protein 2 biosynthesis, Insulin-Like Growth Factor I biosynthesis, Male, Polymerase Chain Reaction, RNA, Messenger analysis, Transforming Growth Factor beta metabolism, Tumor Necrosis Factor-alpha metabolism, Insulin-Like Growth Factor Binding Proteins biosynthesis, Lung Diseases, Interstitial metabolism, Pulmonary Alveoli metabolism, Somatomedins biosynthesis
- Abstract
The involvement of the insulin-like growth factor (IGF) system in lung growth and repair following injury is sustained by a number of studies. Based on this knowledge, the aim of the present work was to document the expression of the IGFs and their binding proteins by alveolar cells obtained by bronchoalveolar lavage (BAL). Two groups were investigated: a control group of five children and a group of 11 children referred to the department for exploration of interstitial lung disease (ILD). Components of the IGF system studied included IGF-I, IGF-II and IGF-binding proteins (IGFBP). Expression of these factors was analysed at the level of messenger ribonucleic acid (mRNA) (by semi-quantitative reverse transcription polymerase chain reaction techniques), and of protein for the IGFBPs. In addition, expression of two major cytokines associated with the inflammatory process, tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), was also documented. In children without parenchymal disease, the growth factor expressed was IGF-I, in association with the presence of mRNA for IGFBP-2 in all cases. In children with ILD, expression of IGF-I was observed in nine patients and of IGF-II in three patients, and the presence of IGFBP-2 was found in all extracts analysed (mRNA and proteins). Evaluation of IGFBP-2 expression indicated an increase in the group of children with ILD. Interestingly, a significant association was observed between the increase in IGFBP-2 expression and TGF-beta expression. The present data emphasize the presence on insulin-like growth factor-binding protein-2 in the BAL of all patients, and suggest that this protein may be an important factor of the injury/repair processes during the progression of alveolar inflammation.
- Published
- 1998
- Full Text
- View/download PDF
8. Identification of three novel mutations in the CFTR gene, R117P, deltaD192, and 3121-1G-->A in four French patients.
- Author
-
Feldmann D, Sardet A, Cougoureux E, Plouvier E, Fontaine JL, Tournier G, and Aymard P
- Subjects
- Adolescent, Amino Acid Substitution, Base Sequence, Child, Child, Preschool, DNA chemistry, DNA genetics, DNA Mutational Analysis, Female, France, Humans, Male, Mutation, Point Mutation, Sequence Deletion, Cystic Fibrosis genetics, Cystic Fibrosis Transmembrane Conductance Regulator genetics
- Published
- 1998
- Full Text
- View/download PDF
9. Longitudinal study of Aspergillus fumigatus strains isolated from cystic fibrosis patients.
- Author
-
Neuvéglise C, Sarfati J, Debeaupuis JP, Vu Thien H, Just J, Tournier G, and Latgé JP
- Subjects
- Adolescent, Aspergillosis prevention & control, Aspergillus fumigatus genetics, Child, Child, Preschool, DNA Fingerprinting, Female, Humans, Longitudinal Studies, Male, Molecular Epidemiology, Recurrence, Time Factors, Aspergillosis epidemiology, Aspergillosis genetics, Aspergillus fumigatus isolation & purification, Cystic Fibrosis complications, DNA, Fungal analysis
- Abstract
The colonization over time of cystic fibrosis patients by Aspergillus fumigatus was investigated using a DNA fingerprinting method. Aspergillus fumigatus isolates collected sequentially for more than one year from six patients with cystic fibrosis were typed by Southern blot hybridization with a repetitive DNA sequence. Each cystic fibrosis patient harbored several strains of Aspergillus fumigatus that were isolated recurrently over time. Isolates collected from a cystic fibrosis patient with aspergilloma displayed the same genotype, suggesting that the infection was due to a single strain. Continuous isolation of the same genotype in another cystic fibrosis patient, however, was not correlated clinically with an Aspergillus infection.
- Published
- 1997
- Full Text
- View/download PDF
10. Mycobacterial lung disease in cystic fibrosis: a prospective study.
- Author
-
Fauroux B, Delaisi B, Clément A, Saizou C, Moissenet D, Truffot-Pernot C, Tournier G, and Vu Thien H
- Subjects
- Adolescent, Bacterial Infections diagnosis, Bacteriological Techniques, Child, Child, Preschool, Female, Humans, Incidence, Infant, Lung microbiology, Male, Mycobacterium growth & development, Mycobacterium Infections epidemiology, Prospective Studies, Spirometry, Sputum microbiology, Cystic Fibrosis complications, Lung Diseases microbiology, Mycobacterium Infections diagnosis
- Abstract
Background: Patients with cystic fibrosis (CF) may be predisposed to airway infections with unusual organisms, such as mycobacteria. The aim of the study was to determine the incidence and clinical picture of mycobacterial infection in CF children., Methods: At least 2 acid-fast bacillus (AFB) smears and mycobacterial cultures were performed on a prospective basis on 682 sputum specimens from 106 patients during a 1-year period., Results: Thirty-three percent of the cultures were contaminated with other bacteria. Seven children had at least one sputum culture positive for one mycobacterium. Five children had only one positive AFB culture. Their clinical status and lung function remained stable during follow-up. Two teenagers with severe lung disease had several positive AFB smears and cultures for Mycobacterium chelonae and Mycobacterium abscessus. The isolation of M. chelonae and M. abscessus was associated with a clinical and functional decline. Clarithromycin treatment resulted in temporary improvement with the disappearance of the mycobacteria after 6 months of treatment. This prospective study shows an incidence of 2.3% for positive cultures. The prevalence was 6.6% for mycobacterial colonization but only 1.9% for mycobacterial lung disease in our pediatric population., Conclusions: We recommend performing AFB smears and cultures in CF children with severe lung disease and/or during a lung exacerbation. In these patients persistence of M. chelonae or M. abscessus in sputum should lead to consideration of treatment with clarithromycin.
- Published
- 1997
- Full Text
- View/download PDF
11. Colonization by Alcaligenes xylosoxidans in children with cystic fibrosis: a retrospective clinical study conducted by means of molecular epidemiological investigation.
- Author
-
Moissenet D, Baculard A, Valcin M, Marchand V, Tournier G, Garbarg-Chenon A, and Vu-Thien H
- Subjects
- Adolescent, Child, Electrophoresis, Gel, Pulsed-Field, Female, Humans, Male, Polymerase Chain Reaction, Retrospective Studies, Alcaligenes isolation & purification, Cystic Fibrosis microbiology
- Published
- 1997
- Full Text
- View/download PDF
12. Adrenobronchial fistula complicating a neonatal adrenal abscess: treatment by percutaneous aspiration and antibiotics.
- Author
-
Pointe HD, Osika E, Montagne JP, Prudent M, Tournier G, and Sebbouh D
- Subjects
- Abscess diagnostic imaging, Abscess drug therapy, Adrenal Gland Diseases diagnostic imaging, Adrenal Gland Diseases drug therapy, Adrenal Gland Diseases microbiology, Anti-Bacterial Agents administration & dosage, Cefotaxime administration & dosage, Cefotaxime therapeutic use, Cephalosporins administration & dosage, Cephalosporins therapeutic use, Contrast Media administration & dosage, Gentamicins administration & dosage, Gentamicins therapeutic use, Humans, Infant, Newborn, Injections, Intravenous, Male, Needles, Netilmicin administration & dosage, Netilmicin therapeutic use, Suction, Tomography, X-Ray Computed, Abscess complications, Adrenal Gland Diseases etiology, Anti-Bacterial Agents therapeutic use, Bronchial Fistula etiology, Escherichia coli Infections diagnostic imaging, Escherichia coli Infections drug therapy, Fistula etiology, Lung Diseases etiology
- Abstract
A case of retroperitoneal pulmonary fistula caused by a neonatal adrenal abscess is reported. The adrenal abscess was diagnosed by means of needle aspiration which guided the choice of antibiotic therapy. The fistula was demonstrated by direct injection of contrast medium into the adrenal abscess. Treatment by needle aspiration of the adrenal abscess and intravenous antibiotics was successful.
- Published
- 1997
- Full Text
- View/download PDF
13. CFTR gene analysis in cystic fibrosis patients: detection of 91% of molecular defects and identification of the novel mutation D979V.
- Author
-
Plouvier E, Cougoureux E, Sardet A, Tournier G, Aymard P, and Feldmann D
- Subjects
- Adolescent, Child, Child, Preschool, Cystic Fibrosis diagnosis, Electrophoresis, Polyacrylamide Gel methods, Exons, Female, Humans, Infant, Male, Middle Aged, Mutation, Cystic Fibrosis genetics, Cystic Fibrosis Transmembrane Conductance Regulator genetics
- Abstract
More than 600 mutations have been identified in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene and are known to cause cystic fibrosis (CF). This large number of mutations makes the search of the molecular defects in CF patients difficult. We have used the techniques of denaturing gradient gel electrophoresis (DGGE) and direct DNA sequencing to detect the mutations in 334 CF chromosomes mostly of French origin. The whole coding sequence of the CFTR gene corresponding to the 27 exons and their exon-intron boundaries was studied. 45 different mutations were identified. This method allowed us to detect the molecular defect in 90.5% of the mutant alleles and to report a novel mutation D979V.
- Published
- 1997
14. Idiopathic pulmonary fibrosis in infants.
- Author
-
Osika E, Muller MH, Boccon-Gibod L, Fauroux B, Sardet A, Grosskopf C, Couvreur J, Tournier G, and Clement A
- Subjects
- Biopsy, Bronchoalveolar Lavage, Bronchoscopy, Fatal Outcome, Female, Glucocorticoids therapeutic use, Humans, Infant, Male, Oxygen Inhalation Therapy, Pulmonary Fibrosis diagnosis, Pulmonary Fibrosis therapy
- Abstract
Idiopathic pulmonary fibrosis is a poorly characterized disease in infants. In the present report, we reviewed our experience with 10 infants during a 10-year period. In 9 patients, onset of symptoms occurred before the age of 2 months and included tachypnea, cough, and inadequate weight gain. However, despite the presence of these symptoms, diagnosis was delayed for 3 months at which time the infants were referred to the pediatric pulmonary department, when the diagnosis was confirmed by open lung biopsy. At the time of admission, bronchoscopy with alveolar lavage was performed in 9 children and showed severe alveolitis with an increase in the neutrophil count. Nine infants were treated with prednisone alone or in combination with chloroquine, colchicine, or cyclophosphamide; all these patients died despite treatment. One infant was treated with pulses of methylprednisolone because of a failure in response to oral prednisone. This girl who displayed similar clinical, radiological, and histological abnormalities as the other children at the time of diagnosis is the only child still alive after 3 years of follow-up. She is now free of respiratory symptoms and has a normal growth curve. The present report raised two important points: (1) a thorough evaluation of characteristic symptoms should lead to an early diagnosis of pulmonary fibrosis in infants; and (2) administration of pulse therapy using corticosteroids has been helpful and needs to be evaluated further.
- Published
- 1997
- Full Text
- View/download PDF
15. Molecular epidemiology of Burkholderia cepacia, Stenotrophomonas maltophilia, and Alcaligenes xylosoxidans in a cystic fibrosis center.
- Author
-
Vu-Thien H, Moissenet D, Valcin M, Dulot C, Tournier G, and Garbarg-Chenon A
- Subjects
- Alcaligenes isolation & purification, Burkholderia Infections complications, Burkholderia cepacia isolation & purification, Child, Child, Preschool, Colony Count, Microbial, Cross Infection complications, Cross Infection epidemiology, Cystic Fibrosis complications, Gram-Negative Bacterial Infections complications, Humans, Incidence, Molecular Epidemiology, Xanthomonas isolation & purification, Alcaligenes growth & development, Burkholderia Infections epidemiology, Burkholderia cepacia growth & development, Cystic Fibrosis microbiology, Gram-Negative Bacterial Infections epidemiology, Xanthomonas growth & development
- Abstract
Burkholderia cepacia, Stenotrophomonas maltophilia, and Alcaligenes xylosoxidans have been isolated with increasing frequency from the sputum of patients with cystic fibrosis in a pediatric hospital. In 1994-95, 27 of 120 patients were persistently colonized, 17 with Burkholderia cepacia, eight with Alcaligenes xylosoxidans, and five with Stenotrophomonas maltophilia. Genotyping of 220 clinical isolates revealed that most of the Burkholderia cepacia strains were clonally related, suggesting either cross-infection or a common source of exposure. In contrast, neither cross-infection nor a common source of exposure appear to have occurred in the cases of Alcaligenes xylosoxidans or Stenotrophomonas maltophilia.
- Published
- 1996
- Full Text
- View/download PDF
16. Pseudomonas (Burkholderia) cepacia in children with cystic fibrosis: epidemiological investigation by analysis or restriction fragment length polymorphism.
- Author
-
Valcin M, Moissenet D, Sardet A, Tournier G, Garbarg-Chenon A, and Vu-Thien H
- Subjects
- Adolescent, Anti-Bacterial Agents pharmacology, Burkholderia cepacia drug effects, Burkholderia cepacia isolation & purification, Child, Child, Preschool, Drug Therapy, Combination pharmacology, Electrophoresis, Gel, Pulsed-Field, Female, France, Hospitals, Pediatric, Humans, In Vitro Techniques, Male, Burkholderia cepacia genetics, Cystic Fibrosis microbiology, DNA, Bacterial chemistry, Polymorphism, Restriction Fragment Length, Pseudomonas Infections microbiology
- Abstract
Since 1987, Pseudomonas cepacia has been isolated with an increasing frequency in the expectorants of children with cystic fibrosis followed at the Hôpital d'enfants Armand Trousseau (Paris, France). Colonization by P. cepacia may be responsible for serious secondary infections and rapid deterioration in respiratory function in these patients. Among the 130 children attending our centre, 14 (8 girls and 6 boys) aged 3 to 18, exhibited chronic colonization. 132 isolates, originating from sputum obtained between 1992 and 1994 were studied. Nine biochemical patterns and 6 antibiotic susceptibility patterns at least were defined, therefore exhibiting great polymorphism. Chromosome restriction patterns with Xba I after pulsed field gel electrophoresis enabled 4 pulsotypes to be identified: A, B, C and D. Thirteen patients harboured pulsotypes A, C and D, and 1 patient pulsotype B, the last being quite distinct from the first three. Pulsotypes A, C and D were almost similar, suggesting that closely related strains, probably the same strain, was harboured by 13 of the 14 patients. The origin could be contamination from a single source, or stem from patient-to-patient crossed transmission.
- Published
- 1996
17. Cytotoxic drug-induced pulmonary disease in infants and children.
- Author
-
Fauroux B, Meyer-Milsztain A, Boccon-Gibod L, Leverger G, Clément A, Biour M, and Tournier G
- Subjects
- Acute Disease, Adolescent, Adrenal Cortex Hormones therapeutic use, Child, Child, Preschool, Chronic Disease, Female, Humans, Infant, Lung Diseases, Interstitial diagnosis, Lung Diseases, Interstitial drug therapy, Male, Respiratory Function Tests, Retrospective Studies, Survival Analysis, Treatment Outcome, Antineoplastic Agents adverse effects, Lung Diseases, Interstitial chemically induced
- Abstract
The increased survival rate of malignant diseases due to more aggressive treatments contributes to the occurrence of drug-induced pulmonary diseases (DIPD). We reviewed, retrospectively over a 10-year period, 15 children (8 girls) who presented a DIPD. Their mean age was 9 years (range, 1 to 17 years), with an underlying malignant disease in 14 (9 leukemias). Three typical patterns have emerged from this analysis: (1) acute hypersensitivity lung disease caused by methotrexate (in 6 patients) or azathioprine (in 1 patient). This acute syndrome consisted of alveolar-interstitial infiltrate with a hypercellularity on bronchoalveolar lavage (BAL) (mean, 714,286 cells/mL; range, 180,000-2,940,000 cells/mL) and an increase of lymphocyte counts (mean, 39%; range 11-64%) with predominantly CD8-suppressor/cytotoxic lymphocytes. Inhibition of leukocyte migration or leukocyte aggregation in the presence of low drug concentrations was positive in the 5 cases tested. Lung function tests showed a restrictive pattern and the outcome of DIPD was always favorable. (2) Chronic pneumonitis/fibrosis was seen in 6 patients who received a variable association of cyclophosphamide (3 patients), bleomycin (2 patients), BCNU (2 patients), and melphalan (1 patient). Symptoms of an alveolar-interstitial pneumonitis developed progressively. BAL showed a moderate increase of total cell numbers (mean, 495,000 cells/mL; range, 150,000-900,000 cells/mL). Lung function tests showed a restrictive pattern. Despite corticosteroid treatment in 4 children, one died after bleomycin lung injury and 2 had functional lung impairment. (3) Noncardiogenic pulmonary edema occurred in 2 patients with leukemia treated with recombinant interleukin II. BAL showed hypercellularity and outcome was rapidly favorable.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1994
- Full Text
- View/download PDF
18. Sarcoidosis of the upper respiratory tract in children.
- Author
-
Roger G, Gallas D, Tashjian G, Baculard A, Tournier G, and Garabedian EN
- Subjects
- Adenoidectomy, Adenoids surgery, Adolescent, Bronchoscopy, Female, Granuloma, Giant Cell surgery, Humans, Male, Nasal Obstruction etiology, Prednisone administration & dosage, Prednisone therapeutic use, Sarcoidosis complications, Sarcoidosis drug therapy, Adenoids pathology, Granuloma, Giant Cell pathology, Sarcoidosis diagnosis
- Abstract
Sarcoidosis is a multisystemic granulomatosis of unknown etiology which mainly affects young adults. It is characterized primarily by bilateral hilar adenopathies, a pulmonary infiltrate and cutaneous and ocular lesions. It rarely occurs in children under the age of 16. Localization in the upper respiratory tract (URT) is infrequent and sarcoidosis of the URT in children is exceptional, with only 13 cases reported in the literature. In the present report we describe the clinical, diagnostic explorations, histological and therapeutic aspects of 2 new cases in children.
- Published
- 1994
- Full Text
- View/download PDF
19. Resting energy expenditure in infants with cystic fibrosis.
- Author
-
Girardet JP, Tounian P, Sardet A, Veinberg F, Grimfeld A, Tournier G, and Fontaine JL
- Subjects
- Anthropometry, Basal Metabolism, Eating, Female, Humans, Infant, Infant, Newborn, Male, Rest, Cystic Fibrosis metabolism, Energy Metabolism physiology
- Abstract
To evaluate the contribution of energy expenditure to the energy imbalance seen in cystic fibrosis patients, resting energy expenditure was measured using open-circuit indirect calorimetry in eight infants with cystic fibrosis, aged 2-7 months (mean, 4), without overt lung disease and in 10 healthy age-matched controls. In both groups, we found close, significant, linear correlations between resting energy expenditure and body weight and between resting energy expenditure and fat-free mass as measured by anthropometry. Cystic fibrosis patients had a 26% increase in resting energy expenditure per kilogram of fat-free mass as compared with controls and a 32% increase in resting energy expenditure as compared with predicted values for fat-free mass. These data from young infants free of clinical symptoms suggest a constitutional metabolic disorder in cystic fibrosis and support the need for early nutritional therapy in cystic fibrosis patients.
- Published
- 1994
- Full Text
- View/download PDF
20. Pulmonary sarcoidosis in children: serial evaluation of bronchoalveolar lavage cells during corticosteroid treatment.
- Author
-
Chadelat K, Baculard A, Grimfeld A, Tournier G, Boule M, Boccon-Gibod L, and Clement A
- Subjects
- Adolescent, Bronchoscopy, CD4-CD8 Ratio, Child, Female, Follow-Up Studies, Humans, Lung Diseases diagnosis, Lung Diseases drug therapy, Lung Diseases immunology, Male, Prednisone therapeutic use, Recurrence, Respiratory Function Tests, Sarcoidosis diagnosis, Sarcoidosis drug therapy, Sarcoidosis immunology, Bronchoalveolar Lavage Fluid cytology, Lung Diseases pathology, Macrophages, Alveolar pathology, Sarcoidosis pathology, T-Lymphocyte Subsets pathology, T-Lymphocytes pathology
- Abstract
The clinical course of sarcoidosis in children has not been well defined. Eight children with symptomatic sarcoidosis included in this study underwent pulmonary function tests and bronchoscopy with bronchoalveolar lavage (BAL) before treatment and during steroid therapy. At the start of therapy, functional parameters, mostly dynamic lung compliance and lung transfer factor for CO, were impaired. This was associated with abnormalities of BAL cell populations: increased total cell number with a high proportion of lymphocytes, modifications of lymphocyte subpopulation with an elevated CD4+/CD8+ ratio, and enhanced ability of alveolar macrophages to release hydrogen peroxide. Although respiratory abnormalities seemed to be similar at the initial stage of sarcoidosis in children and adults, the course of the disease appeared to be different. Despite the absence of respiratory symptoms and disappearance of chest radiographic abnormalities on prolonged steroid treatment, we found slow improvement of pulmonary functions associated with persistence of BAL lymphocytosis and elevated CD4+/CD8+ ratios. However, the ability of alveolar macrophages to release hydrogen peroxide was significantly reduced after 6 months of steroid treatment, and it remained identical to the control group. Therefore, the evaluation of disease activity appears to be critical for therapy in pediatrics, and for this purpose studies of alveolar macrophage activation may be of particular interest.
- Published
- 1993
- Full Text
- View/download PDF
21. Miliary tuberculosis with acute respiratory failure and histiocytic hemophagocytosis. Successful treatment with extracorporeal lung support and epipodophyllotoxin VP 16-213.
- Author
-
Monier B, Fauroux B, Chevalier JY, Leverger G, Nathanson M, Costil J, and Tournier G
- Subjects
- Adolescent, Female, Histiocytosis, Non-Langerhans-Cell complications, Humans, Radiography, Respiratory Insufficiency complications, Syndrome, Tuberculosis, Miliary complications, Tuberculosis, Miliary diagnostic imaging, Etoposide therapeutic use, Extracorporeal Membrane Oxygenation, Histiocytosis, Non-Langerhans-Cell therapy, Respiratory Insufficiency therapy, Tuberculosis, Miliary therapy
- Abstract
A 14-year-old girl with high fever, dyspnea and bilateral miliary nodules on chest X-ray, developed a rapidly progressive respiratory failure associated with histiocytic hemophagocytosis. Histologic examination of bone marrow biopsy revealed tuberculous granulomas with caseating necrosis. We report a pediatric case in which treatment with extracorporeal lung support and epipodophyllotoxin VP 16-213 was successful.
- Published
- 1992
- Full Text
- View/download PDF
22. Control of breathing in children with interstitial lung disease.
- Author
-
Gaultier C, Perret L, Boule M, Tournier G, and Girard F
- Subjects
- Adolescent, Age Factors, Child, Child, Preschool, Elasticity, Female, Humans, Hypoxia physiopathology, Lung Volume Measurements, Male, Oxygen physiology, Pulmonary Fibrosis physiopathology, Respiration
- Abstract
Control of breathing at rest was studied in 14 children (4-16 years old) with interstitial lung disease (ILD). Four of them were tested several times. Breathing pattern and the mouth occlusion pressure (P0.1) were measured. Results in ILD children were compared to values in healthy children previously reported. Respiratory frequency and minute ventilation were increased (P less than 0.02). Inspiratory time (TI) was shortened (P less than 0.001), the shortening in TI being significantly related to the increase in lung elastance (EL). The ratio of TI to the total duration of the respiratory cycle (TI/TTOT) was lowered (P less than 0.01). Tidal volume (VT) both in ml and normalized for body weight (BW) was normal. P0.1 was higher than predicted. The increase in P0.1 was significantly related to change in arterial O2 pressure (PaO2) which was reduced in 10 cases. There was a significant relationship between the increase in P0.1 and in EL. The increase in mean inspiratory flow (VTBW/TI) was related to the increase in EL. But VTBW/TI was not increased as much as P0.1. Consequently the effective inspiratory impedance was enhanced. This high effective inspiratory impedance was related to the increased lung elastance.
- Published
- 1982
- Full Text
- View/download PDF
23. Decreased phosphatidyl choline content in bronchoalveolar lavage fluids of children with bronchopulmonary dysplasia: a preliminary investigation.
- Author
-
Clement A, Masliah J, Housset B, Just J, Garcia J, Grimfeld A, and Tournier G
- Subjects
- Bronchopulmonary Dysplasia metabolism, Humans, Infant, Newborn, Lung analysis, Oxygen blood, Oxygen Inhalation Therapy, Proteins analysis, Respiration, Artificial, Respiratory Insufficiency complications, Respiratory Insufficiency therapy, Retrospective Studies, Therapeutic Irrigation, Bronchopulmonary Dysplasia etiology, Phosphatidylcholines analysis
- Abstract
Bronchoalveolar lavage (BAL) was performed on 12 infants who had recovered from neonatal acute respiratory failure and on 12 patients with bronchopulmonary dysplasia (BPD) in order to evaluate the concentration of phosphatidyl choline (PC) in BAL fluid. These two groups were similar at birth (mean birth weight: 1,980 and 1,750 g, respectively; mean gestational age: 33.4 and 32.1 weeks respectively). Mechanical ventilation based on oxygen requirement lasted longer in the group with BPD. BAL was performed at the end of the first year of life (at 8.5 and 10.3 months, respectively) and the results were compared to control values (from infants of the same age without neonatal disease). Whereas the protein concentration in BAL fluid was similar in the two groups, a dramatic decrease of the BAL PC was found in BPD: The mean values of BAL-PC over protein ratio were 0.9 in the group without pulmonary sequelae and 0.3 in the group with BPD. These preliminary results suggest an impairment of the pulmonary surfactant metabolism in this chronic lung disease following neonatal acute respiratory failure.
- Published
- 1987
- Full Text
- View/download PDF
24. Respiration during sleep in children with COPD.
- Author
-
Gaultier C, Praud JP, Clément A, D'Allest AM, Khiati M, Tournier G, and Girard F
- Subjects
- Child, Preschool, Diaphragm physiopathology, Female, Humans, Infant, Infant, Newborn, Male, Muscle, Smooth physiopathology, Wakefulness physiology, Lung Diseases, Obstructive physiopathology, Respiration, Sleep physiology
- Abstract
Seventeen children (mean age, nine years) with chronic obstructive pulmonary disease (COPD) were studied during sleep. Electroencephalography, electrooculography, and electromyography were all recorded. Airflow was measured by nasal and oral thermistors, and abdominal and thoracic anteroposterior diameters by magnetometers. Transcutaneous partial pressure of O2 (tcPO2) and of CO2 (tcPCO2) were monitored. The average total sleep time was 283 min +/- 36 (1 SD). Breathing pauses (BP) five seconds or longer were measured. The mean time of BP expressed as a percentage of TST was 1.3 percent +/- 0.8 (1 SD). The BP occurred most frequently during REM sleep. Forty-six percent of BP were obstructive (OBP). The percentage of OBP was significantly related to the degree of lung resistance during wakefulness. Periodic breathing was observed with a mean frequency of 2.2 times per night (range: 0 to 7). Episodes with paradoxic inward rib cage motion were seen one to 29 times (mean 6.6). Drops in tcPCO2 greater than 5 mm Hg occurred one to eight times and 67 percent were observed during REM sleep. Compared to tcPCO2 during W the mean maximal decrease in tcPCO2 was 14 mm Hg (range 8 to 29). tcPCO2 rose with a mean maximal of 9.1 mm Hg (range 6 to 13). It was concluded that children with COPD had worsened gas exchange during sleep.
- Published
- 1985
- Full Text
- View/download PDF
25. Effects of naloxone on the control of breathing in children with chronic obstructive pulmonary disease.
- Author
-
Gaultier C, Boulé M, Tournier G, and Girard F
- Subjects
- Bronchi drug effects, Child, Endorphins physiology, Female, Humans, Lung Compliance drug effects, Lung Volume Measurements, Male, Pulmonary Ventilation drug effects, Lung Diseases, Obstructive drug therapy, Naloxone pharmacology, Respiration drug effects
- Abstract
The effect of naloxone on occlusion pressure (P0.1), the pattern of breathing and the expiratory flows during spontaneous ventilation was studied in 16 children with chronic obstructive pulmonary disease under control conditions, after isotonic saline injection and 5 (N5) and 25 (N25) min after i.v. injection of naloxone (2 micrograms X kg-1). At N5, no change was observed in tidal volume normalized for body weight (VTBW), inspiratory time (TI), respiratory frequency (f), mean inspiratory flow (VTBW/TI) and the ratio of TI and total duration of the respiratory cycle (TI/TT). P0.1 decreased significantly (p less than 0.001) at N5 and returned to control values at N25. The decrease in P0.1 without any change in the breathing pattern suggests that naloxone has an effect on respiratory mechanics. Indeed, at N5, the expiratory flows generated at 25% of VT, measured on the flow-volume curves during spontaneous ventilation, increased significantly when compared to control values. Moreover, the decrease of P0.1 after naloxone was found to be correlated to the reduction of dynamic lung compliance (CLdyn) (p less than 0.02). It is speculated that peripheral airway obstruction, as reflected by the decrease in CLdyn, might be a triggering factor for the release of endorphins. The bronchodilation observed after naloxone could then be due to naloxone's antagonistic effect on endorphin-induced bronchoconstriction.
- Published
- 1983
26. A controlled study of oxygen metabolite release by alveolar macrophages from children with interstitial lung disease.
- Author
-
Clement A, Chadelat K, Masliah J, Housset B, Sardet A, Grimfeld A, and Tournier G
- Subjects
- Adolescent, Bronchoalveolar Lavage Fluid cytology, Bronchoalveolar Lavage Fluid metabolism, Cell Separation methods, Child, Child, Preschool, Female, Humans, Hydrogen Peroxide metabolism, Infant, Macrophage Activation drug effects, Macrophages drug effects, Male, Superoxides metabolism, Macrophages metabolism, Oxygen Consumption, Pulmonary Alveoli metabolism, Pulmonary Fibrosis metabolism
- Abstract
The ability of alveolar macrophages (AM) to release O2 metabolites was studied in 8 children with interstitial lung disease (ILD), and in 11 children without lung parenchyma disorder. AM were collected by bronchoalveolar lavage. The experiments were performed on unstimulated AM and on AM stimulated by phorbol myristate acetate (PMA) or zymosan. Our results indicated that, with or without triggering agent, the amount of O2 metabolites release was a linear function pattern with time. The accumulation of superoxide anion (O2-) and hydrogen peroxide (H2O2) into the extracellular medium differed depending on the triggering agent used: with PMA, the amount of O2- released was threefold the amount of H2O2 detected in the medium, whereas with zymosan the O2- accumulation was tenfold higher than the amount of H2O2 measured. In patients with ILD, a significant increase in the amount of H2O2 release was observed for both unstimulated and stimulated AM (p less than 0.001). In this group, the measurement was repeated after a 2-month steroid treatment: prednisone had markedly improved the clinical, radiologic, and functional status of the patients, and this improvement was in good correlation with the decrease of O2 metabolite production. The amount of H2O2 release in each case was within the range of control values. Evaluation of O2 metabolite release by AM could be a useful parameter in the assessment of the activity of ILD.
- Published
- 1987
- Full Text
- View/download PDF
27. Lung function in children with recurrent bronchitis.
- Author
-
Boule M, Gaultier C, Tournier G, Allaire Y, and Girard F
- Subjects
- Bronchitis blood, Carbon Dioxide blood, Child, Child, Preschool, Female, Humans, Infant, Lung Compliance, Lung Volume Measurements, Male, Oxygen blood, Recurrence, Respiration, Bronchitis physiopathology, Lung physiopathology
- Abstract
Lung function was studied in 29 children suffering from recurrent bronchitis (average number of bronchitis attacks per year: 4.2 +/- 0.5). Most of them (73%) were 1--7 years old. The date of exploration in relation to the last acute bronchitis was on average 6 weeks. Lung mechanics, residual functional capacity, blood gases and regional lung function were measured. Most of the children were suffering from some kind of functional disorder; alteration of lung mechanics -- increase of lung resistance (22/29) decrease of dynamic compliance (15/23); increase of functional residual capacity (6/10), non specific bronchial hypersensitivity (12/17); regional ventilatory and perfusion malfunction. These functional disorders could be the first evidence of the bronchial lesions which cause chronic obstructive bronchitis in adults.
- Published
- 1979
- Full Text
- View/download PDF
28. Inspiratory force reserve of the respiratory muscles in children with chronic obstructive pulmonary disease.
- Author
-
Gaultier C, Boulé M, Tournier G, and Girard F
- Subjects
- Adolescent, Child, Female, Functional Residual Capacity, Humans, Male, Respiratory Function Tests, Rest, Risk, Tidal Volume, Time Factors, Total Lung Capacity, Lung Diseases, Obstructive physiopathology, Muscles physiopathology, Respiration, Respiratory System physiopathology
- Abstract
The purpose of this study was to evaluate inspiratory muscle force reserve in children with chronic obstructive pulmonary disease (COPD). In 15 hyperinflated (FRC/TLC, 65 +/- 0.7%) children, maximal mouth inspiratory static pressure (PImax) at FRC, mouth occlusion pressure (P0.1), tidal volume (VT), inspiratory time (TI), and total duration of the respiratory cycle (Ttot) were all measured. It was found that PImax at FRC was reduced compared with predicted values. However, after lung volume correction, PImax was in the normal range, and P0.1 was higher, TI was shorter, and Ti/Ttot was lower than predicted. The estimated mean inspiratory pressure for breathing at rest (PI) was significantly higher than predicted and was related to total pulmonary resistance (r = 0.74, p less than 0.001). The fraction of PImax developed by the respiratory muscles for breathing at rest (PI/PImax) significantly increased. The higher the PI/PImax ratio, the more the TI/Ttot ratio decreased (r = -0.64, p = 0.01). At rest, our subjects had to develop a mean inspiratory power (W) of as much as 48% (range, 30 to 76%) of the critical W above which fatigue occurs. Thus, even minimal increases in breathing load might expose children with COPD to respiratory muscle fatigue and to respiratory failure.
- Published
- 1985
- Full Text
- View/download PDF
29. Activation of alveolar macrophages from children with the acquired immunodeficiency syndrome-related complex.
- Author
-
Clement A, Sardet A, Chadelat K, Grimfeld A, and Tournier G
- Subjects
- Bronchoalveolar Lavage Fluid immunology, Cell Count, Cell Migration Inhibition, Child, Child, Preschool, Female, Humans, Hydrogen Peroxide biosynthesis, Male, AIDS-Related Complex immunology, Bronchoalveolar Lavage Fluid pathology, Macrophage Activation
- Abstract
The ability of alveolar macrophages (AM) to release hydrogen peroxide (H2O2), an indicator of AM function, was studied in five children with the acquired immunodeficiency syndrome (AIDS) related complex and, for comparison, in 11 children without disorders of the lung parenchyma. In the AIDS-related complex group, pulmonary manifestations were mild, and lung involvement was suspected by moderate clinical and/or radiological features. None had a past history of opportunistic infections; neither did any have lymphopenia. Cytologic study of the bronchoalveolar lavage (BAL) fluid revealed increased cellularity with increased percentage of lymphocytes. The study of H2O2 release was performed on unstimulated AM and on AM stimulated by phorbol myristate acetate (PMA). Under both experimental conditions, the amount of H2O2 accumulated in the medium was significantly increased in the group with AIDS-related complex (P less than 0.001). As no enhanced oxidative activity has been reported in AM from patients with full-blown AIDS, an increased ability of AM to release oxygen metabolites from children with AIDS-related complex may reflect an initial and temporary step in the course of the LAV/HTLV-III pulmonary disease. Determining AM activation might be a reliable method of assessing the evolution of lung disorder in AIDS.
- Published
- 1988
- Full Text
- View/download PDF
30. Alveolar macrophage status in bronchopulmonary dysplasia.
- Author
-
Clement A, Chadelat K, Sardet A, Grimfeld A, and Tournier G
- Subjects
- Bronchopulmonary Dysplasia drug therapy, Bronchopulmonary Dysplasia metabolism, Cell Adhesion, Cells, Cultured, Humans, Hydrogen Peroxide metabolism, Infant, Infant, Newborn, Pulmonary Alveoli cytology, Pulmonary Alveoli metabolism, Bronchopulmonary Dysplasia immunology, Prednisone therapeutic use, Pulmonary Alveoli immunology
- Abstract
The predominant inflammatory cell type within the alveolar structure in bronchopulmonary dysplasia (BPD) is the alveolar macrophage (AM). AM ability to release hydrogen peroxide, a way to evaluate the cell status, was studied in nine infants who developed clinical and radiological evidence of BPD, and was compared to those from infants without lung parenchymal disorders (n = 6). AM were collected by bronchoalveolar lavage which was done after the mechanical ventilation stage in the BPD group. The experiments were performed on unstimulated AM and on AM stimulated by phorbol myristate acetate. Results revealed that the amount of hydrogen peroxide accumulated in the culture medium was significantly enhanced in the BPD group, in both experimental conditions (p less than 0.01 and less than 0.001, respectively). Furthermore, improvement of patients treated with glucocorticoids was closely related to a reduction of the alveolitis with a decrease of AM ability to generate hydrogen peroxide. These data indicate that AM activation is a central component of alveolitis in BPD and that extracellular production of oxidants by stimulated AM may play a critical role in the pathogenesis of the disease.
- Published
- 1988
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.