[New therapeutic approaches to Cystic fibrosis]. / Récentes approches thérapeutiques de la mucoviscidose.

Since the cloning of the defective gene in cystic fibrosis, much has been learned on the function of CFTR and on the mechanisms regulating its expression. Based on the current understanding of the processes involved in lung disease progression, a number of approaches have been developed using gene therapy and pharmacological agents. Several of these agents have been reported to restitute a function to CFTR with specific mutations. Other molecules act on channels other than CFTR, and may be effective by bypassing CFTR itself. In the present review the various therapeutical strategies currently investigated are discussed.

Optimization of aerosol deposition by pressure support in children with cystic fibrosis: an experimental and clinical study.

Nebulized aerosols are commonly used to deliver drugs into the lungs of patients with cystic fibrosis (CF). The aim of this study was to assess the effectiveness of pressure-support (PS) ventilation in increasing aerosol deposition within the lungs of children with CF. An in vitro study demonstrated the feasibility of coupling a breath-actuated nebulizer to a PS device. An in vivo study was done with 18 children (ages 6 to 21 yr) with clinically stable CF, each of whom underwent both a standard and a PS-driven ventilation scan (control session and PS session, respectively). In addition, a perfusion scan was used to determine lung outlines and to construct a geometric model for quantifying aerosol deposition by radioactivity counting in MBq. Homogeneity of nebulization was evaluated from the four first-order moments of aerosol distribution in the peripheral and central lung regions. The time-activity nebulization curve was linear in all patients, with higher slopes during the PS than during the control session (0.43 +/- 0.07 [mean +/- SD] MBq/min and 0.32 +/- 0.23 MBq/min, respectively; p < 0.018). Quantitatively, aerosol deposition was about 30% greater after the PS session (4.4 +/- 2.7 MBq) than after the control session (3.4 +/- 2.1 MBq; p < 0.05). Similarly, deposition efficacy (as a percentage of nebulizer output) was significantly better during the PS session than during the control session (15.3 +/- 8.3% versus 11.5 +/- 5.7%, p < 0.05). No differences in the regional deposition pattern or in homogeneity of uptake were observed. In conclusion, our data show that driving the delivery of a nebulized aerosol by noninvasive PS ventilation enhances total lung aerosol deposition without increasing particle impaction in the proximal airways.

Experimental study of antidiarrheal activity of Salicairine.

Experimental antidiarrheal activity of a traditionally used medication, Salicairine, was demonstrated in comparison to loperamide by significant inhibition of castor oil-induced diarrhea in mice (increases in hard faeces/total faeces ratio of 38 and 54 and 5 and 54% with respect to controls, at 0.5 and 1 mL/kg and 1 and 2 mg/kg, respectively) and bisacodyl-induced increase in large intestine transit in rats (125 and 280 and 210% with respect to controls, at 0.4 and 2 mL/kg Salicairine and 5 mg/kg loperamide, respectively). Salicairine was able to reduce contractions of isolated rat duodenum induced by barium chloride and acetylcholine, although not completely (that is about 60%) as seen with loperamide. Also, it did not change normal gastrointestinal transit in mice at doses of 0.5 to 1 mL/kg, conversely to loperamide which had a significant effect (decrease of 50%) at 2 mg/kg. Finally, Salicairine at 0.01 mL/mL, like loperamide at 0.2 mg/mL, significantly increased net fluid absorption in rat colon, either in basal conditions (30 and 64% respectively) or after a prostaglandin E1-induced increase in net fluid secretion (41 and 35%, respectively). The antidiarrheal activity of Salicairine is possibly related, at least in part, to an increase in colon net fluid absorption or a decrease in net fluid secretion.

Aerosol-mediated delivery of recombinant adenovirus to the airways of nonhuman primates.

At present, it is conceivable that gene therapy of the cystic fibrosis airway epithelium is possible using the direct transfer of a functional human cystic fibrosis transmembrane conductance regulator (CFTR) gene to a wide variety of patients' tracheo-bronchial cells. Here we describe a novel approach (aerosolization) to deliver a replication-deficient adenovirus carrying the CFTR gene (Ad.CFTR) to the airways. Results obtained in vitro and in Rhesus monkeys suggest that the delivery of recombinant adenovirus as an aerosol is feasible and is not associated with severe toxicity after single or double administration depending on the Ad.CFTR dose. This study supports the concept of aerosolization as a delivery method for adenovirus-mediated lung gene therapy.

[Limiting tests of benzyle halides or heavy alkyles in tensioactive and antimicrobial quaternary ammonium salts]. / Essais limites d'halogénures de benzyle ou d'alkyles lourds dans les sels d'ammoniums quaternaires tensioactifs et antimicrobiens.

As working material at the final stage of the synthesis of tensioactive and antimicrobial quaternary ammoniums salts, the alcoyles halides residuums have been let aside. The author developed limiting tests about these impurities particularly on the benzododecinium bromide. Four alternative methods are thus proposed.

[Amiloride hydrochloride nebulized by oxygen in the treatment of mucoviscidosis]. / Etude d'un nébulisat de chlorhydrate d'amiloride véhiculé par de l'oxygène dans la mucoviscidose.

Bronchial inhalation of amiloride chlorhydrate has been suggested for a number of years in the treatment of the pulmonary disease in cystic fibrosis. However, physiotherapy remains invaluable in the struggle in containing pulmonary infections in this disorder. Physiotherapy may lead to a transient fall in the arterial oxygen as can sessions of nebuliser therapy which precedes physiotherapy. The originality of the system studied and proposed here for the administration of medication depends on an electronic control which guarantees that there is the nebulisation of a constant volume of medication with each inspiration. Triggered by inspiration the active principle nebulised is perfectly co-ordinated to the inspiratory cycle. A comparative chromatography carried out in this slides of silica-gel have enabled us to verify the absence of any degradation of the active principle contained in the nebuliser solution during the ten minutes period of aerosol therapy. Thus a quantification of the administered dose of Amiloride Chlorhydrate is made possible. In association with oxygen it enables an efficacious preparation of respiratory physiotherapy to children. As the expiratory tubing ends in a filter the fraction of the oxygen inhaled by the patient remains very high; 80% (V/V) of the medication is emitted in the form of liquid particles whose diameter lies between 0.5 and 5 micrometers. In practice in order to humidify the sputum and to restore the oximetry before the physiotherapy sessions, it seemed to us an interesting possibility to administer Amiloride Chlorhydrate and oxygen simultaneously. This is achieved in hospital by using wall-mounted oxygen (at a gas pressure of 3.5 bars).(ABSTRACT TRUNCATED AT 250 WORDS)

[An automatic gas scanning device, technical improvement for obtaining a favourable atmosphere for in vitro culture of anaerobic bacteria]. / Balayage gazeux à l'aide d'un automate, une amélioration technique d'obtention d'une atmosphère propice à la culture en jarre des bactéries anaérobies.

All methods for growth of anaerobic bacteria on solid media depend on the elimination of atmospheric O2 through use of a palladium catalyst (Deoxo-Catalyst), active in presence of at least 5% H2 with resultant formation of water. Anaerobic chambers and jars are the two conventional methods employed. Both are based on the elimination of air by means of a pump and its replacement with gas from a cylinder (evacuation-replacement technique). An alternative chemical technique for use in anaerobic jars consists of adding internal gas-generating sachets. The former techniques are more efficient but the trend, particularly in the clinical laboratories, is to use the simpler chemical system that has two inconveniences: a slow establishment of anaerobiosis, and a high cost. We propose a new system that does not require a vacuum pump and consists in flushing anaerobic jars with a convenient gas mixture (H2, CO2, N2: 4.5; 5; 90.5 v/v) by means of an automaton regulating both time and gas flow. Gas-liquid chromatography analysis of the gas inside the jar shows a rapid elimination of gaseous O2, whose residual concentration is low enough to permit growth of all anaerobes of clinical interest, including those which are more O2-sensitive. Comparative qualitative and quantitative data obtained with all available techniques demonstrate the advantages of the new system.

Interstitial pneumonitis and pulmonary vasculitis in a patient taking an L-tryptophan preparation.

A case is presented of interstitial pneumonitis and pulmonary vasculitis ascribed to the ingestion of an L-tryptophan preparation. An unintended rechallenge supported the causal relationship. There was neither myalgia nor peripheral eosinophilia. Bronchoalveolar lavage fluid contained 12% eosinophils but few were present in the surgical lung biopsy specimen. Lung infiltrates receded after withdrawal of the drug and treatment with steroids. Dyspnoea and pulmonary hypertension persisted. Cyclophosphamide had no effect. Sclerodermiform skin lesions appeared as a late sequel. Chromatographic analysis of the L-tryptophan revealed no suspect impurities.

The beginnings of otorhinolaryngology in Belgium in the 10th Century

Belgian ear-nose throat speciality is one hundred fifty years old. It started with the family Delstanche (father and son), Michaux and Verhaeghe had also much interest in it. We shall also speak about Delie, Hicguet, Rousseau, Schiffers, De Beco, Hennebert, Eeman, delstanche third generation, Van den Wildenberg, jauquet, Capart, Goris and Cheval

[Palatine amygdalectomy through the ages]. / L'amygdalectomie palatine à travers les âges.

This paper describes the development of the techniques of amygdalectomy through the ages. It would appear that Susruta de Bénares performed such an operation as early as the first century, but I personally have no documents on him. On the other hand, the operation is described in scrupulous detail by Celse, at the same period, and was not greatly different from our current dissection. The Judeo-Arab world was familiar with amygdalectomy from the very beginning, and the techniques of Abulcassis, Avicenne and Haly Abbas used dissection, pulling-out and cauterization as early as the 10th century. Guillemeau, a student of Paré, was the first to propose a ligature. In the 18th century, Benjamin Bell remained faithful to the ligature technique, and devised on uvulotome, which gave Physick the idea of an amygdalotome, from which derived the instrument of Sluder-Ballenger, incorrectly called the guillotine, given that its principle was based on pulling-out rather than cutting. Nevertheless, dissection remains today the technique most widely employed.

History of rhinology: functional surgery of the nose in France at the turn of the century.

The first reference to an attempt at functional surgery of the nose which we have discovered in France concerns Blandin (Paris 1798-1849) who "corrected" septal deviations with a punch; one arm is introduced into each nostril. Heylen performed a submucous resection in 1847, Chassaignac in 1851 and Demarquay in 1859 through the external median columellar route. In 1876 Richet carried out a resection of the deviated septum after having elevated the whole cartilaginous pyramid, achieved by a horizontal incision of the base of the columella. Paul Berger recommended, in 1883, a subperichondrial chisel resection of the salient part of the septum. In 1888, Miot approached septal thickening with galvano-caustic chemicals using metal plates or through a method called galvano-puncture. In 1892 Escat resected the cartilaginous arch and its corresponding mucosa after having separated the contralateral mucosa with injected water. In 1903, Caboche referred to both operations used at that time to correct cartilaginous septal deviations, e.g. Petersen's operations (submucous resection) and Asch's operation (fracture with repositioning). In 1905, Blanc distinguished between three types of operations: 1. Procedures based upon the fracturing the septum or its straightening and its maintenance with a splint. 2. Procedures designed in order to overcome the elasticity of the cartilage by making incisions followed by its retention in place. 3. Submucous resection of the cartilage based upon the principle that the septum is too big for its surroundings. In 1917, Dangouloff and Woyatchek developed a septoplasty technique, many modern operations being only pale copies of theirs. It consisted of four possibilities: mobilization, straightening, circular resection and partial resection.

[Indications, technic and long-term results of surgery of the nasal pyramid and septum in children]. / Indications, technique et résultats à long terme de la chirurgie de la pyramide nasale et de la cloison chez l'enfant.

Since the operation of submucous resection of the septum has been replaced by septoplasty, the indication for nasal surgery in children has increased. They may be divided into four categories, which by order of importance are: Re-establishment of nasal function (95%); severe nasal allergy provoked by deformity; psychological factors associated with deformities and cosmetic factors related to gross congenital deformities. Septoplasty must preserve three zones: Central zone, the anterior edge of the septum and supra-premaxillary region. Rhinoplasty is less dangerous than septoplasty in children. Surgery of the turbinates is often necessary in conjunction with the preceding operations. The authors present several examples of long term results (before and after puberty).