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Biomedical subjects

D Dusser

Publications and source records attributed to D Dusser.

At least 55 records · Page 3Linked to original sources

[Physiological roles of the respiratory epithelium].

The epithelium of the airways plays a complex role in the organism's defence system against aggressive inhaled agents. Classically, the continuous cell layer of the epithelial mucosa acts as a protective barrier, but physiological role is much more complex and varied. The airway epithelium transports secretions by a collaborative effect of the ciliary movements and the rheological properties of the mucosa resulting from hydro-electrolytic movements occurring transepithelially. The epithelium participates in bronchial inflammatory response by interactions with inflammatory cells in the mucosal itself and by its capacity to produce free radicals and inflammatory mediators. Its membrane enzymes also participate in regulating neurogenic inflammation. A further role involves repairing damage which could compromise mucosal integrity. The airway epithelium participates in the immune defence system by interacting with lymphocytes and probably also by its capacity to express class II HLA molecules responsible for antigen presentation. Finally, the epithelium participates in anti-infectious mechanisms via its micro-organism receptors, its relationship with immune cells and inflammatory cells, its participation in mucociliary clearance and finally by the secretion of antiinfectious molecules (lysozymes, free radicals) by the mucosa.

Bronchi↗

Unexpected inactivation of acceptor consensus splice sequence by a -3 C to T transition in intron 2 of the CFTR gene.

Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Analysis of DNA from a pancreatic sufficient patient by means of denaturing gradient gel electrophoresis (DGGE) and subsequent DNA sequencing led to the identification of a novel potential splice mutation and a novel missense mutation in the CFTR gene. One C to T substitution (297-3C-->T) was found at the splice acceptor site of intron 2 and a T to C substitution at 1213 was found in exon 7. To determine the effect of the potential splicing mutation on the patient's CFTR transcripts and by taking advantage of the "illegitimate" transcription phenomenon, RNA from EBV-lymphoblastoid cells was reverse transcribed and amplified by the polymerase chain reaction (PCR). Direct sequencing of the PCR product revealed that the transcript from the chromosome with the 297-3C-->T mutation exhibited the skipping of exon 3.

Adult↗

[Cystic fibrosis: gynecological and obstetrical aspects].

Survival in patients with cystic fibrosis has considerably improved over the last years. Young adults are particularly concerned. Fertility in these patients is greatly decreased, especially in men due to obstructive azoospermia. In women, intra-uterine insemination with her spouse's sperm can overcome anomalies in the cervical glair. Several pregnancies in patients with cystic fibrosis have been reported, especially in women with a mild form of the disease. Prematurity is frequent, about 35% as is perinatal mortality related to the mother's status. When lung involvement is severe leading to major obstruction and hypoxia, cor pulmonae and denutrition, pregnancy remains a contraindication. Care for pregnant women (when pregnancy is possible) should rely on a multidisciplinary team and include a rigorous nutritional and anti-infection support.

Adult↗

A French version of the Sickness Impact Profile (SIP): stages in the cross cultural validation of a generic quality of life scale.

The Sickness Impact Profile is a quality of life scale developed in the United States which is now widely used in clinical trials in chronic conditions such as chronic obstructive lung disease, angina, rheumatoid arthritis, chronic pain, psoriasis, inflammatory bowel disease and cancer. Validated generic scales permit cross cultural comparisons within disease processes in clinical trials. As a simple, direct translation of a scale is inadequate, we have created a French version of the original US version of the Sickness Impact Profile. The first phase was qualitative. A first French translation of the original US version was back translated into English by three independent translators. A second French version resulted from a consensus reached by a panel of lay subjects and health professionals after comparing the original US version, the first French version and the three back translations. This second version was tested with a group of 40 healthy volunteers. This qualitative phase resulted in a French Test Version with content and face validity. The quantitative phase assessed the equivalence of the rank order of each item, by sub scale, in the US version with that of the French Test Version, ie the rank of the French item was comparable (+/- 2) to the rank of the corresponding US item. The French Test Version was tested with 47 healthy subjects. Of the 136 items of the Sickness Impact Profile, 13 were retranslated to create a final French version. This was similarly tested on ten healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of inflammation and fibrosis on pulmonary function in diffuse lung fibrosis.

To investigate the relation between lung function and inflammation and fibrosis in patients with diffuse lung fibrosis, a study was made of untreated patients without appreciable airway obstruction (14 patients with cryptogenic fibrosing alveolitis and seven with pneumoconiosis). Quantitative assessment of inflammatory infiltration and fibrosis was carried out on open lung biopsy specimens and compared with lung volumes, carbon monoxide transfer factor (TLCO), TLCO corrected for alveolar volume (TLCO/VA), and arterial blood gases at rest and during exercise. The degree of fibrosis and the degree of cellular infiltration were positively correlated. Lung volumes and TLCO were correlated with the grades of fibrosis and cellular infiltration of alveoli; arterial blood gases during exercise tended to correlate with both fibrosis and infiltration (p less than 0.06). In contrast, morphological data were not correlated with gas exchange at rest or with TLCO/VA. It is concluded that, in untreated patients with diffuse lung fibrosis, lung volumes, TLCO, and arterial blood gases during exercise reflect the lung lesions, and that the pulmonary function tests used cannot discriminate between fibrosis and infiltration of the lung by inflammatory cells.

Adult↗

Lung function declines in patients with pulmonary sarcoidosis and increased respiratory epithelial permeability to 99mTc-DTPA.

Respiratory epithelial clearance of 99mTc-DTPA (RC-Tc-DTPA) and pulmonary function tests (PFT) were determined at intervals of 6 or 12 months in 37 untreated, nonsmoking patients with sarcoidosis over a period of 6 to 36 months. PFT included the measurements of total lung capacity (TLC), vital capacity (VC), FEV1, and diffusing capacity for carbon monoxide. No difference was found between the respiratory clearance of 113mIn-DTPA (2.25 +/- 1.00%/min) and RC-Tc-DTPA (2.29 +/- 1.11%/min) in eight patients with pulmonary sarcoidosis. Pulmonary function decreased 15% or more in at least 2 function tests during 11 follow-up periods, but it remained stable during 47 follow-up periods. In patients whose lung function deteriorated, RC-Tc-DTPA increased to 3.51 +/- 1.55%/min; in contrast, in patients whose lung function remained stable, regardless of the initial values, RC-Tc-DTPA was normal (1.00 +/- 0.50%/min; p less than 0.001). In eight patients who were treated with corticosteroids, RC-Tc-DTPA decreased from 3.48 +/- 1.31%/min to 1.56 +/- 0.64%/min (p less than 0.001), and PFT improved. We conclude that in nonsmokers with pulmonary sarcoidosis, increased RC-Tc-DTPA is not related to dissociation of 99mTc from DTPA, RC-Tc-DTPA is increased when pulmonary function decreases, and, when increased, RC-Tc-DTPA decreases with corticosteroid therapy.

Adult↗

Toluene diisocyanate increases airway responsiveness to substance P and decreases airway neutral endopeptidase.

Substance P and related tachykinins contribute to the airway hyperresponsiveness caused by toluene diisocyanate (TDI) in guinea pigs. Neutral endopeptidase (NEP) is an important modulator of substance P-induced responses. To test the hypothesis that exposure to TDI would increase responsiveness to substance P by inhibiting activity of this enzyme, we determined the dose of substance P required to increase pulmonary resistance by 200% above baseline (PD200) before and after administration of the pharmacologic inhibitor phosphoramidon in guinea pigs studied 1 h after a 1-h exposure to air or 3 ppm TDI. TDI exposure increased responsiveness to substance P significantly. However, phosphoramidon caused a significantly greater leftward shift of the substance P dose-response curve in air-exposed animals than it did in TDI-exposed animals, so that after phosphoramidon, mean values of PD200 in animals exposed to air or TDI did not differ. Tracheal NEP activity was significantly less after exposure to TDI than after exposure to air, whereas activity in the esophagus was the same in both groups. These results suggest that TDI exposure increases the bronchoconstrictor responsiveness of guinea pigs to substance P, in large part through inhibition of airway NEP.

Airway Resistance↗

Comparison between theophylline analysis by nephelometric inhibition immunoassay and high performance liquid chromatography.

Rate nephelometric inhibition immunoassay (NIIA) was used to determine 94 serum theophylline concentrations, and these results were compared with those obtained using high performance liquid chromatography (HPLC) as a reference method. The measurements obtained by the nephelometric method were, on the average, 20% higher than those obtained by the chromatographic method (p less than 0.001). The coefficient of variation of the nephelometric method was 12.3%, compared with 3.9% for the chromatographic reference method. In the group of subjects having a serum concentration of caffeine greater than or equal to 0.5 microgram ml-1, the difference in serum theophylline concentration found between NIIA and HPLC correlated with serum caffeine concentration (r = 0.3755, df = 46, p less than 0.01). NIIA theophylline concentration was 8.8 +/- 3.2 micrograms ml-1 in serum from six additional patients receiving theophylline 9.1 +/- 3.4 micrograms ml-1 after adding 10 micrograms caffeine (NS), and 13.1 +/- 3.5 micrograms ml-1 after adding 10 micrograms 1,3-dimethyluric acid (p less than 0.001). We conclude that (a) the results obtained by the NIIA method are more variable and consistently higher than those obtained by the HPLC method and (b) 1,3-dimethyluric acid (a caffeine and theophylline metabolite) is responsible for this overevaluation.

Adult↗

Effectiveness of micronic aerosol generators and their aerosol characteristics.

We assessed the effectiveness of various aerosol-generating systems. Taplin's settling method and Venticis generators had a lower efficiency (37.3 +/- 3.8% and 51.8 +/- 9.6%, respectively) than the Syntevent (88.8 +/- 6.9%, p less than 0.001), Cadema (89.8 +/- 9.9%, p less than 0.001) and Mefar (85.3 +/- 19.4%, p less than 0.001) generators. The Mass Median Aerodynamic Diameter of the particles produced by the Mefar nebulizer (2.05 +/- 0.27 micron) was larger than that of any other generators (p less than 0.001). The Syntevent (0.54 +/- 0.09 micron) generator produced smaller particles than the Mefar, Taplin (0.89 +/- 0.10 micron, p less than 0.01) and Venticis (0.79 +/- 0.06 micron, p less than 0.02) generators. Particles produced by the Cadema system (0.69 +/- 0.06 micron) were smaller than those generated by the Taplin system (p less than 0.05). We conclude: that the Syntevent, Mefar and Cadema aerosol generators are more efficient than the others, and that all the generators tested except the Mefar may be used for studies that depend on the peripheral deposition of small particles within the lungs.

Aerosols↗