Preliminary results of collapse therapy with plombage for pulmonary disease caused by multidrug-resistant mycobacteria.

Seven patients underwent collapse therapy with polystyrene sphere plombage for pulmonary disease caused by multidrug-resistant mycobacteria. Four patients were infected with multidrug-resistant strains of Mycobacterium tuberculosis, two with Mycobacterium xenopi, one with Mycobacterium avium. All patients were heavily pretreated before surgery, had extensive, bilateral cavitary disease and were considered unsuitable for resection because of extensive disease or functional respiratory impairment. Six patients had active disease at time of surgery. Collapse therapy with insertion of six to 18 spheres resulted in long-standing bacteriological conversion in six patients. Collapse therapy was unilateral in six and bilateral in one. No immediate postoperative complication or death was observed. Hospital stay was short (mean 12 d). Collapse therapy is a conservative alternative therapy in patients with pulmonary disease caused by multidrug-resistant mycobacteria at high risk of treatment failure considered unsuitable for pulmonary resection.

[Value of video-surgery in the treatment of voluminous emphysematous bullae]. / Apport de la vidéo-chirurgie dans le traitement chirurgical des bulles d'emphysème volumineuses.

In general, giant emphysematous bullae develop within the substance of dystrophic pulmonary parenchyma. The bullae impede normal mechanical ventilation by the volume they occupy and by the compression which they exert. This addition can lead to acute complications. It is for these reason that surgery is often indicated until recently. These patients were always operated on by a thoracotomy or sternotomy. The deleterious affects of thoracotomy are of course added to the existing complications of the disease and are performed on patients with respiratory failure whose general state of health is often very poor. The recent arrival of video surgery has raised the hope that post operative problems will be less painful with fewer functional consequences and a reduction of morbidity and mortality. Since 1992 to 1995 24 of our patients have been operated exclusively by this technique for emphysematous bullae which occupy at least one third of the hemithorax. For 15 patients the bullae occupied half of the hemithorax. The functional constraint which can be assessed by Sadoul's classification enables four groups to be isolated: 6 patients in stage 5; five patients in stage 4; nine patients in stage 3; four patients in stage 1. In the preoperative work up, computered tomography occupies first place in assessing the extent of the disease. In our series the mortality was 4 per cent and the overall morbidity 34 per cent. The mean functional benefit between three and 16 months which was evaluated in 11 patients was an improvement of 500 mls for the FEVI and the Vital Capacity. The average increase in PO2, measured in four patients, was 7 mmHg. In 15 patients on whom information was available twelve were found to have complete autonomy. The initial results show that surgery of giant emphysematous bullae can be done using video surgery. It can be hoped that this technique will diminish the morbidity linked to a thoracotomy. Its place in the therapeutic arsenal for the treatment of emphysematous bullae seems to be justified in our eyes.

[First experience in treatment of terminal cardiac insufficiency using multisite stimulation]. / Première expérience de traitement de l'insuffisance cardiaque terminale par la stimulation multisite.

We hypothesized that the presence of an abnormal ventricular mechanical activation sequence and/or a delayed left ventricular (LV) contraction may have adverse hemodynamic effects in congestive heart failure (CHF) and could be improved by synchronous RV-LV pacing in a multisite (MS) configuration. 8 NYHA IV CHF patients were included with a LV delay due to 1/ preexistent pacemaker in 4 pts (2 VVI and 2 DDD); 2/ left bundle branch block in 2 pts; 3/ intraventricular conduction delays in 2 pts. An acute hemodynamic evaluation was performed. Hemodynamics were optimized in standard RV pacing by modifying RV lead position from apex to outflow tract (RVOT) in VVI for AF patients and in VDD for sinus rhythm patients at different AV delays. RV pacing did not change hemodynamics whatever the lead position. BV pacing improved CI by 25% (p < 0.006), V wave by 26% (p < 0.004) and PCWP by 17% (p < 0.01). Chronic implantation was performed in 7pts. LV lead was implanted via the coronary sinus in 2 cases and epicardial via a thoracoscopic approach in the remaining ones. 1 pt died during LV lead implantation. Hemodynamics were tested at 2 months followup (FU). Switching BV pacing off was associated with immediate deterioration. At 6 +/- 6 months Followup 4 pts are stable in Class II. 1 pt died of cardiac cause. 1 pt could be transplanted at 17 months FU. In conclusion, BV pacing through a multisite configuration is feasible and can help in CHF patients managing.

Effects of SCA40 on human bronchi and on guinea pig main bronchi in vitro. Comparison with cromakalim.

The aim of this study was to examine the activity of SCA40, a novel charybdotoxin-sensitive potassium channel opener, against a variety of spasmogens or against electrical field stimulation in guinea pig isolated main bronchi and in human isolated bronchi; the effects of SCA40 were compared with those of cromakalim. Like cromakalim, SCA40 reduced the contractility of guinea pig and human isolated bronchi precontracted with acetylcholine 10(-6) M or neurokinin A 10(-6) M, SCA40 being more efficient and more potent than cromakalim. Moreover, on guinea pig isolated main bronchi, SCA40 can exert a preventive effect on contractions induced by acetylcholine, neurokinin A or capsaicin, that is, it shifts to the right the concentration-effect curves of these substances, whereas cromakalim has no such effect. The effects of cromakalim were antagonized by glibenclamide 10(-5) M, whereas the effects of SCA40 were inhibited by tetraethylammonium (TEA 10(-2) M) and charybdotoxin (3 x 10(-8) M), but this inhibitory effect of TEA was reversed by nifedipine (10(-6) M). Electrical field stimulation of guinea pig isolated main bronchi induced two successive contractile responses. Both contractions were significantly reduced by SCA40 (10(-6) and 10(-5) M) and cromakalim (10(-5) M). Since cromakalim was unable to inhibit the effects of acetylcholine or neurokinin A, it might be suggested that for this latter compound the inhibition seems to take place prejunctionally and to affect the release of neuromediators produced by electrical field stimulation. In contrast, in the case of SCA40, a postjunctional effect seems to be likely, owing to its preventive effects, although a prejunctional effect cannot be excluded. Finally, on guinea pig isolated main bronchi, SCA40 (10(-8)-10(-6) M) did not potentiate the relaxant effect of isoprenaline or sodium nitroprusside, suggesting a lack of functional manifestation of inhibition of phosphodiesterase for these concentrations. In conclusion, these results demonstrate that SCA40 is a potent and efficient relaxant of guinea pig and human airway smooth muscle, and is able to inhibit, in the guinea pig isolated main bronchi, the contractions induced by electrical field stimulation. It has an effect on TEA-sensitive K+ channels, but this effect is probably not involved in its relaxant effect which does not also rest on an inhibitory effect of phosphodiesterase.

[Tracheobronchial cylindroma. Success after left pneumonectomy and plastic repair of a large right tracheobronchial break with a musculo-pleural pedicle and bone graft around a temporary Dumont prosthesis]. / Cylindrome trachéo-bronchique. Succès après pneumonectomie gauche et plastie d'une grosse brèche trachéo-bronchique droite avec pédicule musculo-pleural et greffon osseux autour d'une prothèse provisoire de Dumon.

A 54-year-old woman with a cylindroma of the lower trachea underwent exploration with dissection of the tracheobronchial junction. The main left bronchus was invaded and there was major tissue loss of membranous tracheo-bronchial substance. Histology showed both tracheal and bronchial involvement. Left pneumonectomy was performed and a Dumon prosthesis was installed on the right. The prosthesis was enveloped in a musculopleural plasty reinforced with a vone graft. Good air flow was established immediately allowing secondary reconstruction of a perfectly functional neobronchus. Outcome was quite favorable with a 3 year follow-up.

Beta 3-adrenoceptor agonists, BRL 37344 and SR 58611A, do not induce relaxation of human, sheep and guinea-pig airway smooth muscle in vitro.

The existence of atypical- or beta 3-adrenoceptors has now been generally accepted. These receptors have been shown to be abundant in adipose tissue and in a number of gastrointestinal smooth muscle preparations. A recent study reported that beta 3-adrenoceptor stimulation mediated relaxation of isolated canine bronchial smooth muscle. The aim of the present study was to extend this observation to other species. We investigated the in vitro responses of guinea-pig, human and sheep bronchial smooth muscle to isoprenaline, salbutamol (a selective beta 2-adrenoceptor agonist), and BRL 37344 and SR 58611A (two presumably selective beta 3-adrenoceptor agonists). The preparations were precontracted to 60-70% of maximal tension with histamine 10(-6) M for guinea-pig and human bronchi, or acetylcholine 10(-6) M for sheep bronchi. In each species, SR 58611A produced a slight fall in tension of about 10% of the effects of theophylline (3 mM), but this decrease in tension was not significantly different from the spontaneous and weak relaxation observed with saline addition during the same duration of the experiment. These relaxations were not modified by either the nonselective beta-adrenoceptor antagonist propranolol or the selective beta 2-adrenoceptor antagonist ICI 118,551. In contrast, BRL 37344 induced a significant concentration-dependent fall in tension induced by both spasmogens. Its relaxant effects were inhibited both by propranolol and ICI 118,551 in human and guinea-pig airways, whereas on the isolated sheep bronchus BRL 37344-induced relaxations were only slightly, albeit significantly, reduced with either of the beta-adrenoceptor antagonists tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects on the isolated human bronchus of SR 48968, a potent and selective nonpeptide antagonist of the neurokinin A (NK2) receptors.

Tachykinins produce concentration-dependent contraction of the human isolated bronchus by stimulation of receptors that belong to the NK2 type. The aim of this study was to investigate the inhibitory effects of a new, potent, and selective nonpeptide antagonist of the neurokinin A (NKA) (NK2) receptors, SR 48968 [(S)-N-methyl-N-[4-acetylamino-4-phenylpiperidino-2-(3,4-dichlorophenyl) butyl]benzamide] on human isolated airways. Our experiments were performed on human isolated bronchi obtained from patients with lung cancer. Phosphoramidon, 10(-5) M, was added to the bath to inhibit neurokinin metabolism. SR 48968 induced a parallel shift to the right of the concentration-response (C/R) curves to [Nle10]-NKA(4-10), a specific NK2 receptor agonist. The antagonism was of the competitive type, with a pA2 of 9.40 +/- 0.19 (slope = 0.95 +/- 0.08, n = 13). The (R)-enantiomer of SR 48968 was 100-fold less potent and a noncompetitive antagonist (slope = 0.56 +/- 0.11, n = 8); pA2 and slope of the racemate were 8.86 +/- 0.21 and 1.09 +/- 0.21 (n = 7), respectively. Under similar conditions, racemic CP-96,345, a nonpeptide NK1 antagonist, did not modify the C/R curves to [Nle10]-NKA(4-10) until 10(-7) M. SR 48968 did not modify C/R curves to acetylcholine, histamine, KCI, or PGF2 alpha on the human isolated bronchus. Finally, SR 48968 shifted to the right C/R curves to substance P on isolated human bronchi, whereas racemic CP-96,345 was without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Penetration of minocycline into lung tissues.

The penetration of minocycline into different lung tissues and bronchial mucus was studied in 17 patients undergoing pulmonary surgery for cancer. The patients received oral minocycline 100 mg at night for 3 days preceding surgery. Minocycline concentrations were measured in plasma samples collected before the operation and in tissues and mucus taken from in and around the part of the lung that was surgically removed. Mean tissue or mucus concentration to plasma concentration ratios were 3.78 +/- 1.10 for lung parenchyma, 4.04 +/- 1.31 for bronchial walls, 3.37 +/- 1.00 for pulmonary arterial walls, 1.99 +/- 1.80 for intraluminal mucus collected from bronchi located in healthy tissue proximal to the tumour, 5.16 +/- 3.26 for intraluminal mucus collected in a bronchus distal to the tumour, and 3.06 +/- 1.99 for catheter-collected mucus from the trachea and principal bronchi. These results indicate that minocycline is found in high concentration in all types of lung tissue and mucus in man.

Innominate artery involvement in type IV Ehlers-Danlos syndrome.

We report two cases of innominate artery involvement in patients with Ehlers-Danlos syndrome. In the first patient, spontaneous dissection of the innominate artery was treated successfully. In the other, the patient died of spontaneous rupture of the innominate artery in the early postoperative course after operation for aneurysm of the celiac artery. Arterial complications occurring in Ehlers-Danlos syndrome are rare but pose difficult diagnostic and therapeutic problems for the vascular surgeon due to arterial wall fragility.

[Diffusion of minocycline in pulmonary tissue]. / Diffusion de la minocycline dans le tissu pulmonaire.

The penetration of minocycline into lung tissue was evaluated in 14 patients about to undergo excision of the lung for cancer. The patients received minocycline orally in doses of 100 mg twice a day for 3 days, the 100 mg in the morning of the operation day. Minocycline concentrations were measured in plasma samples taken before surgery and in the lung tissue resected. The mean tissue/plasma concentration ration was 3.17 +/- 0.41 (range: 1.5 to 7.48). The same ratios were obtained in peritumoral and tumoral tissues. These results indicate that minocycline penetrates well into tissues.

Characterization of neurokinin effects and receptor selectivity in human isolated bronchi.

Sensitive afferent nerves and the neurokinins they release upon activation are considered to be important in controlling bronchomotor tone. Human isolated bronchi respond to neurokinin A (NKA), substance P (SP), and neurokinin B (NKB) with dose-dependent contractions. The order of potency of the three natural neurokinins is NKA greater than SP greater than NKB, suggesting the presence of NK-2 receptors. To further characterize the neurokinin receptors in human bronchi, we used selective agonists for each receptor type (i.e., NK-1, NK-2, and NK-3). In fact, NK-1 selective compounds, [Pro9]SP(1-11) sulfone and [beta-ala4,Sar9]SP(4-11) sulfone, did not induce significant contractions up to 10(-5) M. Similarly, the selective agonist for the NK-3 receptor, [MePhe7]NKB(4-10), was almost inactive. However, the NK-2 selective fragment [Nle]NKA(4-10) was a potent stimulant. The negative log of the peptide concentration that caused 50% of maximal effect (pD2) was 6.99 for NKA and 6.12 for [Nle10]NKA(4-10). Removal of the epithelium significantly enhanced the contractile responses to the three neurokinins and also to the NK-2 selective agonist. Phosphoramidon, an enkephalinase inhibitor, was more potent than epithelium removal in enhancing the contractile responses to these agonists. However, epithelium removal and phosphoramidon did not increase the weak responses to the NK-1 and NK-3 selective compounds. In the presence of phosphoramidon, removal of the epithelium slightly enhanced the contractile responses to NKA and [Nle]NKA(4-10) but not to SP and NKB.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction between fenoterol, ipratropium, and acetylcholine on human isolated bronchus.

Functional antagonism between fenoterol (F) and acetylcholine (ACh) and interaction between F and ipratropium (Ipr) on ACh-induced contraction were evaluated on isolated human bronchi. In the presence of increasing concentrations of ACh (2 X 10(-4) and 2 X 10(-3) mol/L), dose-response curves of the relaxant effect of F were shifted to the right (0.45 and 0.92 log units), and the maximal effect of F, expressed as a percentage of the effect of theophylline, 3 X 10(-3) mol/L, was reduced from control values of 92.1 +/- 4% to 70.8 +/- 7.0%, and to 67.2 +/- 7.1%, according to the functional antagonism. In the presence of Ipr, 10(-9) and 10(-8) mol/L, the functional antagonism between ACh and F was partially reversed. Concentration response-curves to F versus ACh, 2 X 10(-3) mol/L, were shifted to the left, and although the -log molar concentration producing 50% of maximal effect was not significantly modified, the maximal effect of F was significantly increased in the presence of Ipr, 10(-8) mol/L. It is concluded that the effect of combined F and Ipr on the isolated human bronchus contracted with ACh appears to be of the additive type.

Effects of noradrenaline on the isolated human bronchus. Comparison with the isolated guinea pig trachea.

The pharmacodynamic activity of noradrenaline was evaluated comparatively in vitro on isolated human bronchi and on guinea pig tracheal spirals. Noradrenaline exerted a contractile effect on both preparations under resting tone and in the presence of propranolol 10(-6) M; maximal noradrenaline-induced contraction was 15-20% of maximal acetylcholine (ACh)-induced contraction. Without propranolol, the contractile effect of noradrenaline was negligible when the preparations were under resting tone and absent when they were precontracted with ACh. In contrast, noradrenaline exerted a strongly relaxant effect on both human bronchi (-log ED50 5.24 +/- 0.17; N = 5) and guinea pig tracheae (-log ED50 6.15 +/- 0.29; N = 8). With maximal contraction induced by ACh 3.10(-3) M the -log ED50 of both preparations were shifted to the right by functional antagonism and became 4.72 +/- 0.17 and 5.31 +/- 0.11, respectively. The pKD values of noradrenaline, calculated according to Furchgott and Bursztyn (1967), were 4.79 +/- 0.04 in human bronchi (N = 5) and 4.77 +/- 0.16 in guinea-pig tracheae (N = 8). In the presence of cocaine plus phenoxybenzamine these values were not significantly modified in human bronchi and only slightly modified in guinea pig tracheae. It is concluded that noradrenaline induces a strong beta-adrenergic response and a negligible alpha-adrenergic response from both human bronchi and guinea pig tracheae in vitro.

[Benign mediastinal hemangiomas]. / Hémangiomes bénins du médiastin.

Haemangiomas represent a very rare form of primary mediastinal tumour. Their benign character, though rare, should not allow one to forget that their excision is correct, though sometimes tricky on account of their special anatomic situation. Two new observations are reported here as evidence of this difficulty. The prognosis, save for a few exceptional cases of local recurrence as in one of the cases sighted here is always good.

[Repair of loss of substance of the thoracic wall and pericardium using a net of resorbable material]. / Réparation des pertes de substance de la paroi thoracique et du péricarde par un filet en matière résorbable.

After wide excision of the chest wall for primary tumour or bronchopulmonary carcinoma involving the ribs, the gap must be filled to prevent paradoxical respiration and its immediate functional consequences during the post-operative period. This can easily be achieved by using a polyglactin 910 piece of net cut to size out of a 25 X 25 cm plaque and sutured between the ribs under tension. The prosthesis ensures thoracic stability and acts as support for re-adherence of the lung to the chest wall. It resists coughing and is well tolerated. The indications of choice are respiratory failure and excision performed in varying degrees of septic condition which make non-absorbable material unsuitable. Another indication is wide excision of a tumour-invaded pericardium with herniation of the heart.