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Biomedical subjects

G Bellon

Publications and source records attributed to G Bellon.

At least 19 recordsLinked to original sources

Delayed compliance increase in infants with respiratory distress syndrome following synthetic surfactant.

Recent research has demonstrated that Exosurf (EXSF), a newly synthesized artificial surfactant, increases survival when administered endotracheally to premature infants with RDS. This study examines the effects of EXSF on static respiratory system compliance (Crs). Thirty-four patients received two doses of EXSF in this rescue protocol. Crs (mL/cmH2O/kg) did not significantly change within the first 4 hours after either dose. However, Crs values did increase significantly (paired Student's t-test, P = 0.005) when data collected after the second dose (0.36 +/- 0.13 mL/cmH2O/kg) were compared to first week follow-up data (0.51 +/- 0.21 mL/cmH2O/kg). Crs data collected between 2 and 4 weeks after treatments were again not significantly different from non-concurrent control data collected at 3-4 weeks of life. The measurement of Crs in infants receiving EXSF may have been affected by an increase in lung inflation, which could mask an increase in Crs. We speculate that improved lung inflation may occur with less barotrauma in the first week of life due to surfactant replacement treatment and may in part explain the improved Crs seen at 1 week of age. Many investigators using different surfactants, dosing schedules, and pulmonary function methodologies to evaluate lung mechanics have reported that the improvement in compliance after surfactant treatment usually follows the clinical improvement in gas exchange. Additional studies are needed to explain the mechanism of early improvement following surfactant replacement in infants with RDS.

Drug Combinations

Heart-lung transplantation in a 16-month-old infant.

A 16-month-old boy who had a heart-lung transplantation is doing well 16 months postoperatively. The HLT can be a successful treatment for very young patients. Most of the postoperative management can be assessed with noninvasive techniques. Normally, the allograph grows with the recipient.

Heart-Lung Transplantation

[From acute viral bronchiolitis in infancy to asthma in childhood].

Bronchiolitis and wheezy bronchitis are frequently associated with viral infection of the respiratory tract in infants. They play an important role in the natural history of chronic obstructive airway disease, not only in children, but also in adults. The risk of early recurrent wheezing and subsequent asthma or chronic bronchitis (with anatomical sequelae such as obliterans bronchiolitis) is significant. The precise pathogenic mechanisms of virus-induced wheezing and its sequelae are not clear. Whether airway hyperreactivity is inherited and airway hyperreactivity is present prior to, or is the result of bronchiolitis is not clear. Nevertheless the evidence for viral trigger of wheezing and long-term pulmonary sequelae must be considered and prevention must be undertaken at the first episode.

Acute Disease

Gamma-interferon inhibits extracellular matrix synthesis and remodeling in collagen lattice cultures of normal and scleroderma skin fibroblasts.

Three-dimensional collagen lattice cultures of fibroblasts mimic the in vivo situation better than monolayer cultures. Here, skin fibroblasts from scleroderma patients and healthy controls were cultivated in collagen lattices, and the effects of recombinant human gamma-interferon (IFN-gamma) on these cultures investigated. IFN-gamma inhibited collagen lattice retraction in a dose-dependent way at concentrations ranging from 10 to 10,000 U/ml. This effect was independent of any alteration to the cell proliferation within the lattices. The inhibition was of the same order of magnitude in normal and pathological fibroblasts. The synthesis of collagen and non-collagen proteins, particularly fibronectin, was increased in scleroderma cultures. It was inhibited in both normal and scleroderma fibroblasts by IFN-gamma, with a maximal effect at the concentration 1000 U/ml, but the inhibition of protein synthesis was far more intense in scleroderma than in normal cells. In situ hybridization, Northern blot and dot blot analyses showed that mRNA coding for pro alpha 1(I) collagen was decreased in IFN-gamma-treated cells, indicating an effect at the pretranslational level. IFN-gamma also inhibited glycosaminoglycan synthesis, but in scleroderma cells only. This study shows that IFN-gamma regulates cell behavior in three-dimensional collagen matrices: (i) it decreases protein and specifically glycosaminoglycan synthesis in scleroderma fibroblasts, (ii) it modulates the interactions between cells and matrix that lead to the retraction of the lattice. Whereas collagen synthesis is largely decreased in lattice cultures like in vivo, it remains increased in the case of scleroderma compared to normal fibroblasts and may be down-regulated by IFN-gamma. Similar conclusions may be drawn for fibronectin and glycosaminoglycans. The inhibitory effect of IFN-gamma on the retraction capacity of fibroblasts and on their ability to synthesize increased amounts of extracellular matrix macromolecules may be of potential interest for therapeutic use of IFN-gamma in scleroderma patients.

Adult

Bovine lens capsule basement membrane collagen exerts a negative priming on polymorphonuclear neutrophils.

After a 30 min contact between purified bovine lens capsule basement membrane type IV collagen and polymorphonuclear neutrophils, stimulation of these cells by N-formyl-methionyl-leucyl-phenylalanine, PMA or type I collagen releases a decreased amount of superoxide ions (negative priming). The inhibitory activity is located in the NCl domain. On the other hand, after pepsin digestion, the helical part of type IV collagen determines a positive priming of neutrophils.

Animals

Plasma dopamine, norepinephrine, epinephrine and DOPAC levels in preterm infants prior to and immediately after a sleep ventilation hypercarbia test.

The postnatal maturation and the adaptational ability of the sympathoadrenal system has been investigated in preterm neonates (n = 8), and in sick preterm neonates with respiratory disorders (n = 10). Plasma levels of dopamine (DA), norepinephrine (NE), epinephrine (E) and 3-4 dihydroxyphenylacetic acid (DOPAC) were evaluated at rest during the first month of life, and following an inhalation of a 5% carbon dioxide-21% oxygen mixture for 10 min. During the first month of life the sick preterm neonates exhibited similar NE, E, and DOPAC plasma levels but higher DA amounts than healthy infants. Plasma DA levels were inversely correlated with the transcutaneous oxygen tension (r = -0.636) indicating that hypoxemia was able to enhance the release of DA. Immediately following the hypercarbia test, there were no significant changes of plasma catecholamine levels in the sick preterms, but there was a significant increase of E plasma levels (+140%, p less than 0.05) and a moderate elevation of NE and DA amounts in the healthy preterms. It is concluded that preterm neonates who have had respiratory disorders did not exhibit an immaturity of the sympathoadrenal system at rest, but had a defect in the release of E following hypercarbia exposure, which may be secondary to an alteration in chemoreceptor function and/or reduced catecholamine stores.

3,4-Dihydroxyphenylacetic Acid

[Determination of nasal transepithelial potential difference (DDPTE) in cystic fibrosis. Analysis of a simplified measurement technique].

Measurements of nasal transepithelial potential differences (TEPD) were performed in 77 patients in order to assess a routine simplified method of recording. TEPD assays were performed in 34 patients with cystic fibrosis aged 1 month to 25 years, in 22 children with another chronic respiratory illness and in 21 subjects without any bronchopulmonary impairment. In the cystic fibrosis group TEPD values (mean +/- SD) were significantly higher (-49.077 +/- 9.38 mV) than in patients with chronic respiratory illnesses (-20.590 +/- 5.011 mV) or in subjects without bronchopulmonary impairment (-19.857 +/- 5.033 mV) (p less than 0.0001). Measurements could not be performed in 10 patients due to major nasal inflammation. The excellent specificity (100%) and sensitivity (93%) of the method confirm its diagnostic value. It may be used from the neonatal period and may represent an alternative to the sweat test, especially in dubious cases.

Child

[Activation of polymorphonuclear neutrophils by contact with collagen I and degradation of collagen].

The contact of polymorphonuclear neutrophils with type I collagen molecules triggers the production of oxygen free radicals by these cells. This activation requires two short collagenic sequences and seems to involve a beta 2 integrin on the neutrophil membrane. Oxygen free radicals are capable to degrade collagen molecules into small peptides. This interaction takes place in inflammatory phenomena.

Collagen

[Aberrant left pulmonary artery and tracheal abnormality].

A case of left pulmonary artery sling and tracheobronchial tree malformation is reported in a 3 month-old infant. Acute respiratory presenting symptoms required mechanical ventilatory support. The malformation was suspected because of ventilatory support difficulties. Barium oesophagogram showed an anterior indentation, fiberoptic bronchoscopy and tracheobronchography showed a severe tracheal stenosis from a right bronchus lobaris superior to the carina. This was worsened by the right side compression of trachea end part, due to the abnormal left pulmonary artery as demonstrated by pulmonary angiography. A surgical left artery transposition relieved lateral compression and allowed weaning of ventilatory support. After a 27 month-follow-up, the girl's respiratory status is satisfactory.

Female

Activation of human neutrophils by type I collagen. Requirement of two different sequences.

Contact between type I collagen purified from several species and human polymorphonuclear neutrophils (PMNs) triggers the production of O2.- by these cells. The activity of collagen is located in the alpha 1(I)-CB6 cyanogen bromide-cleaved (CB)-peptide, which is the C-terminal CB-peptide of the alpha 1(I) chain. Experiments based on the competitive inhibition of O2.- production by simultaneous incubation of PMNs with type I collagen and synthetic peptides identical to the conserved sequences of this collagen demonstrated that the binding of collagen to PMNs and the subsequent activation of these cells depend on the simultaneous presence of two sequences: Arg-Gly-Asp [residues 915, 916 and 917 of the complete alpha 1(I) chain, located in the helical part] Asp-Gly-Gly-Arg-Tyr-Tyr (residues 1034-1039, located in the C-terminal non-helical telopeptide).

Amino Acid Sequence

Human type VI collagen: isolation and characterization of alpha 1 and alpha 2 chains by two-dimensional preparative gel electrophoresis.

Two 140 kDa collagenous glycoproteins were isolated from 5 M guanidinium chloride extracts of human uterine leiomyoma by two-dimensional preparative gel electrophoresis. The glycoproteins represented the major concanavalin A binding fraction of the extract and were also present in adult human skin. On two-dimensional gel electrophoresis the glycoproteins appeared as elongated spots, indicating variations of their isoelectric points from 5 to 6. These glycoproteins were disulfide-bonded components of high molecular mass protein and, after reduction, became sensitive to collagenase treatment that generated peptides corresponding in size to those of the noncollagenous domains of type VI collagen. Antisera raised against these purified glycoproteins reacted with either pepsin-derived alpha 1(VI) or pepsin-derived alpha 2(VI) chains but not with alpha 3(VI) chain of human type VI collagen. Reciprocally, these glycoproteins reacted with monoclonal antibodies against type VI collagen. These results indicate that the glycoproteins represent the integral alpha 1 and alpha 2 chains of type VI collagen. The globular domains of alpha 1(VI) and alpha 2(VI) chains remaining after collagenase treatment appeared on two-dimensional gel electrophoresis as elongated spots, suggesting that the noncollagenous portions determine the well known microheterogeneity of the molecule. The differences in isoelectric points between and within alpha chains may facilitate the formation of microfibrillar network.

Amino Acids

[Cystic fibrosis: choices of treatment of respiratory manifestations (except Pseudomonas aeruginosa infections)].

A knowledge of the natural history of cystic fibrosis is the basis for a treatment which, so far, has only been symptomatic. The three fundamental elements of our therapeutic possibilities are: prevention and treatment of bronchial obstruction, administration of antibiotics active against staphylococci and Haemophilus influenza (Pseudomonas aeruginosa infections will be dealt with in another article of this journal), and control of bronchial inflammatory processes. Some complications of cystic fibrosis regarded as serious are no longer beyond our resources. Many works of fundamental research are needed, concerning the local conditions that are necessary to the selective implantation and the development of Staphylococcus aureus in the lung, and the virus Staphylococcus and Staphylococcus-Pseudomonas relations. The real hope of an absolute treatment justifies the new, aggressive therapeutic approach but the precise indications of an antistaphylococcal treatment must still be evaluated carefully. Finally, the complexity of a treatment which must constantly be adjusted is one of the reasons for the existence of "specialized consultations", the organization of which is summarized.

Airway Obstruction

Effect of prostaglandin E2 on proline uptake and protein synthesis by cultured human mesangial cells.

PGE2 production by glomeruli is increased in a variety of glomerular diseases. Potentially, this process may affect mesangial cell protein synthesis and mesangial cell growth. Thus studies have been undertaken, using cultured human mesangial cells, to assess the effects of PGE2 on proline uptake, protein synthesis and cell proliferation. In the presence of 140 mM NaCl, incubation of mesangial cells with 0.01 to 1 microM PGE2 for 72 hours resulted in a marked decrease of 14C proline uptake, but did not modify 14C leucine uptake. Substitution of choline to sodium inhibited 14C proline uptake by 85% which became independent of PGE2, indicating that this PG specifically altered sodium-dependent proline uptake. Inhibition of this component reached 35 to 50% with 1 microM PGE2. The inhibitory effect of PGE2 on sodium-dependent proline uptake required a lag time of 48 hours, and was suppressed by ouabain, an inhibitor of Na+, K+ ATPase activity. PGE2 did not modify the Vmax of the transport system (1.007 vs. 1.023 nmol/mg/min) but increased (P less than 0.01) its Km (1.179 vs. 0.823 mM). 8-bromo-cyclic AMP also inhibited sodium-independent proline uptake, and PGE2 markedly increased cyclic AMP production. Taken together, these results suggested that PGE2 acted via cyclic AMP stimulation. PGE2 under identical conditions (1 microM, 72 hr incubation) produced a decrease in collagen synthesis estimated by the relative rate of collagen production after incubation of mesangial cells with 14C proline (percentage of 14C radioactivity in collagenase-sensitive proteins over total proteins). PGE2 also diminished the intracellular free proline pool. More generally, PGE2 inhibited cell proliferation and cell total proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division

Stimulation of collagen synthesis in fibroblast cultures by a triterpene extracted from Centella asiatica.

The drug "Titrated Extract from Centella asiatica" (TECA), used for its stimulating properties on the healing of wounds, is a mixture of 3 terpenes extracted from a tropical plant: asiatic acid (30%, w/w), madecassic acid (30%, w/w) and asiaticoside (40%, w/w). The effects of TECA and its individual components were checked on human foreskin fibroblast monolayer cultures. TECA increased the collagen synthesis in a dose-dependent fashion whereas a simultaneous decrease in the specific activity of neosynthesized collagen was observed. Asiatic acid was found to be the only component responsible for collagen synthesis stimulation. TECA and all three terpenes increased the intracellular free proline pool. This effect was independent of the stimulation of collagen synthesis.

Cell Count

[Antibiotic therapy in cystic fibrosis: uncertainty and reality].

Antibiotics inspite of certain contradictions remain an important part of the treatment of mucoviscidosis (MCV). Despite this the current practice of their extensive use does not always rest on firmly placed criteria. Before colonisation with pseudomonas (PA), the systemic prophylaxis of infection by Staphylococcus (SA), or Hemophilus (HI) is debatable. At the time of exacerbations, even if this may be caused by a virus, the prescription of antibiotics (ATB) active against SA and HI should often be continued for 2 or 3 weeks to maintain a durable clinical benefit. While awaiting the results of complimentary multi-centre trials at present underway it remains uncertain whether eradication of the germ at all costs remains indispensable. Systemic anti-PA antibiotic therapy given quarterly from the time of the implantation of the germ has not yet proved to have definitive advantages when compared to the treatment of exacerbations. An appreciation of the benefit of therapy should take count not only of survival curves but also of the quality of life. The indications for treatment should not neglect the possibility of therapeutic progress, sometimes unexpected. Intensive therapy may be justifiable in certain cases awaiting a lung transplant. ATB is only one part of treatment aimed strictly at the broncho-pulmonary system. Drainage and account of infectious agents other than classical bacterial infections or pathogenic mechanisms other than infections (nutritional problems, bronchial hyper-reactivity, immunological phenomenon, or primary or secondary inflammatory changes) should not be ignored.

Anti-Bacterial Agents