Six vs twelve cycles for complete responders to chemotherapy in small cell lung cancer: definitive results of a randomized clinical trial. The "Petites Cellules" Group.

Of 320 patients with small cell lung cancer (SCLC) entered into a clinical trial of chemotherapy between January 1983 and September 1985, 106 patients achieved a complete response. The induction chemotherapy used was lomustine 60 mg.m-2 p.o., cyclophosphamide 1 g.m-2 i.v., doxorubicin 45 mg.m-2 i.v. and etoposide 150 mg.m-2 i.v., every four weeks. Lomustine was only given for the first three cycles. Seventy nine of the 106 patients still in complete response after six chemotherapy cycles were subsequently randomized to receive either six more cycles or no more treatment until relapse. In this group of 79 patients, a difference was shown from the time of inclusion between the 51 patients with limited disease and the 28 patients with disseminated disease, with overall median survivals of 395 and 165 days, respectively, (p = 0.0002). No difference was shown between the two treatment groups: the median survival was 332 days from the time of second randomization with a two year survival rate of 28% for the patients randomized to receive six more cycles and 246 days and 22% for those randomized to receive no more treatment (add 147 days to obtain overall median survival). Continuing chemotherapy for more than six cycles to patients in complete response did not improve survival.

Activity of intrapleural recombinant gamma-interferon in malignant mesothelioma.

Twenty-two consecutive patients with malignant diffuse pleural mesothelioma were treated with recombinant gamma-interferon by the intrapleural route. Diagnosis was made by thoracoscopic examination and all cases were confirmed by the French Mesothelioma Panel of Pathologist. Patients were staged based on thoracoscopic examination and computed tomography (CT) scan: 12 patients were classified as Stage I and 10 were Stage II. A solution of gamma-interferon (40 X 106 U) was infused twice a week over 2 months. Every patient experienced fever. One patient had a Grade 2 leukopenia and one patient suffered from pleural empyema. Response evaluation was based on the following: (1) CT scan performed 2 weeks after treatment ended, and (2) repeat thoracoscopic examination with histopathologic verification in nine patients who had demonstrated a stabilization or a regression of the disease on CT scan. From the original group, 19 patients could be evaluated. Four complete thoracoscopic histopathologic responses and one partial response were observed in Stage I patients (56%). One partial response was observed in Stage II patients.

Amiodarone-induced pulmonary toxicity. Immunoallergologic tests and bronchoalveolar lavage phospholipid content.

Amiodarone (A) is a widely-used antiarrhythmic drug. Pulmonary toxicity is the most serious adverse effect with an estimated mortality of 1 to 33 percent. In order to determine an element helpful for diagnosis, we examined four patients with amiodarone-induced pulmonary toxicity, three patients treated with A, without evidence of pulmonary toxicity but with a main underlying pulmonary disease, and four healthy volunteers. Daily and cumulative doses or duration of treatment were similar in the first two groups. Pulmonary function tests (spirometry, CO-diffusing capacity, arterial blood gases), roentgenographic examinations, pulmonary biopsies or immunoallergologic tests (skin reaction, lymphoblastic transformation test and human basophile degranulation test) did not provide any discriminatory element. In APT+, we observed an increased cellularity of the bronchoalveolar lavage. Neither the differential cell count nor the presence of foamy macrophages were distinguishable between APT+ and APT-. The phospholipid composition of BAL fluid showed a decreased total phospholipid and phospholipid/protein ratio in all patients compared to normal subjects. These changes reflect more the severity of pulmonary disease than the specificity of the causative agent. However, we observed that the unique PL which decreases in APT- and remains normal in APT+ is phosphatidyl-serine + phosphatidylinositol (PS + PI). This has to be confirmed and should be evaluated at different stages of the disease to determine an eventual specific element. We conclude that there are no data currently available to establish the diagnosis of APT except perhaps for the analysis of BAL PL content.

[Tumoral markers and monoclonal antibodies]. / Marqueurs tumoraux et anticorps monoclonaux.

The frequency of malignant pleuritis in general practice and its often difficult diagnosis have led to the ever increasing use of tumoral markers (TMs) which may overcome these difficulties and of immunocytochemical methods which may improve the results obtained by routine cytology. TMs are used in the diagnosis: a) to detect false-negative results and sometimes exclude false-positive results of cytology ("reactive" mesothelial cells); b) to distinguish reliably between malignant mesothelioma and metastatic pleuritis from an undetected adenocarcinoma, and c) to provide additional information, if needed, on the nature and origin of a malignant pleuritis. In pleural carcinology, TMs can be used as part of various methods which may be biochemical (assays of the marker in serum and, more important, in pleural fluid), cytochemical or immunocytochemical, histochemical or immunohistochemical, cytogenetic and cytofluorimetric. TMs can be defined and classified as follows: 1) intrinsic tumoral cell abnormalities; 2) substances associated with tumours which either induce them in the body without any specificity or secrete first generation TMs such as CEA, hyaluronic acid, NSE, ect.; 3) tumour-related antigens recognized by monoclonal antibodies or second generation markers. These markers, extremely varied, are directed against cell and often cell membrane antigens. They are not always very specific. When assayed separately their diagnostic sensitivity is low, but when used in batteries and combined with routine cytology they may fulfill the objectives listed above and fairly significantly improve the results of cytology. As last resort, they can be used in immunomorphology on cytology or biopsy specimens and provide a decisive answer.

[Mediastinal tuberculous adenopathies in Djibouti. Report of 159 cases]. / Les adénopathies médiastinales tuberculeuses à Djibouti. Rapport de 159 cas.

One hundred and fifty-nine cases of confirmed mediastinal tuberculous adenopathy were analysed retrospectively. This series, which is the first reported in French-speaking Africa, shows that the disease is not uncommon there, and not restricted to black Africans living in Europe. The clinical symptoms are not specific. Radiography is more interesting, and the extreme scarcity of bacillys-containing expectoration encourages endoscopy. The finding of a fistula at fibroscopy confirms the diagnosis. This easy examination is particularly useful since M. tuberculosis can be grown in cultures from ground bronchial fistula biopsies in 86% of the cases. Associated tuberculous lesions in other sites are very frequent (45%), as is extension of the disease from lymph nodes to lung tissue (79%). This clinical form of tuberculosis can be treated with modern short course chemotherapy which is remarkably effective.

[Infection and asthma]. / Infection et asthme.

Infection is frequent in all stages and forms of asthma. It is a source of exacerbations of all degrees of severity. Bacterial infection, especially with commensal organisms from the upper respiratory tract, may cause bronchial hyperreactivity (HRB) by various mechanisms, specific--microbial delayed hypersensitivity, probably rate; IgE-dependent hypersensitivity others non-specific: bronchial inflammation, source of mediators of bronchial constriction; activation of complement, direct histamine liberation; beta blockage...; or mixed mechanisms. Respiratory viral infection probably plays the most important role in the natural history of asthmatic disease, especially in infants and young children by inducing or amplifying HRB and creating a transitory obstructive syndrome of the small airways. This virus-induced HRB may develop into a respiratory syncytial virus viraemia at first or remain latent found by tests of bronchial activity. The pathogenic mechanisms of this HRB are often multi-factorial and interlinked: they are chiefly linked to the various cytopathic effects of the virus on the respiratory epithelium, to the viral inflammation; but also to disturbance of the equilibrium of the autonomous nervous system (beta blockage, excitation of the cholinergic receptors); finally in some areas, to virus-induced amplification of the local and systemic immune responses by IgE that favours clinical consideration of atopy.

[Bronchial hyperreactivity in non-asthmatic patients harboring a uterine fibroma]. / Hyperréactivité bronchique chez des patientes non asthmatiques porteuses d'un fibromyome utérin.

One of the etiological factors of female late onset asthma lies in endocrine disorders and it often occurs during a period of hormonal instability (menopause or premenopause). Moreover various studies have shown increased allergic manifestations in women with gynecological problems (dysmenorrhea, premenstrual syndrome). Gynecological pathology is found in 30% of 67 women who suffer from late onset asthma. Prospective studies were carried out in 28 women with surgical uterine fibroma, to investigate bronchial hyperreactivity (BHR). The study included atopic research through questioning and allergy skin tests; spirographic respiratory function study, airway resistance, carbachol BHR with determination of the threshold dose (FEV1 20% decrease). Carbachol BHR was found in 8/28 persons (28%), but with no clinical manifestations. None of the patients smoke and only one suffers from mite-allergic rhinitis-conjunctivitis without asthma. BHR is often found in asymptomatic women with uterine fibroma. Is this BHR due to an autonomic dysregulation or to a hormonal malfunction? This hypothesis would require further studies to elucidate, since premenstrual asthma worsening is a well known phenomenon, which can be improved by progesterone. This may suggest a possible link between hormonal malfunction and BHR in women. A long term survey will facilitate detection of late onset asthma.

[Cardiac tolerance of a beta 2-sympathomimetic spray in 37 asthmatic adults monitored by Holter recording]. / Tolérance cardiaque d'un bêta 2-sympathomimétique en spray chez 37 adultes asthmatiques suivis par enregistrement Holter.

Thirty-seven asthmatic adults (27 women, 10 men), aged 28 to 70 yrs (mean 50. yrs), in a stable condition, were studied to assess the cardiac tolerance of B2SM sprays. These patients had no cardiac arrhythmia (checked by echocardiography), no hypertension and no hyperthyroidism. Two thirds had severe asthma, and 16 suffered from chronic asthma. After their condition was stabilized, they continued their previous treatment, consisting of theophylline (34 cases), moderate corticotherapy (19 cases), atropine spray (14 cases). Holter monitoring was performed before and 3 days after the institution of treatment by Fenoterol spray at 1,600 micrograms per day in 4 doses at fixed times. Gasometry was tested immediately before and during the protocol. Before B2SM treatment, 26 patients had a normal Holter, 11 had an abnormal first recording (4 important atrial ectopic beats (EBs), 5 ventricular EBs, 1 associating the two), 1 patient had an episode of ventricular tachycardia (VT). With Fenoterol, we observed (with no clinical manifestation) the aggravation of 1 pre-existing atrial EBs and 2 ventricular EBs. Two patients had a short episode of tachycardia but the role of Fenoterol was uncertain: one case was an elderly hypoxaemic patient and in the second a high theophylline level (20 mg/l) was found. The arrhythmogenic property peculiar to B2SM in spray form seems low at the dose we used. However in this study and in certain circumstances, such as hypoxemia, metabolic acidosis, or theophylline overload, the use B2SM may have contributed, together with other factors, to induce disquieting infraclinical cardiac dysrhythmia. We stress that this short-term study involved stable asthmatic patients under surveillance in hospital conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of legionellosis among adults: a study of community-acquired pneumonia in France.

Over a 24-month period, 274 patients with community-acquired pneumonia were hospitalized in Departments of Medicine at hospitals in Bordeaux, Lyon, Marseille, and Toulouse. Etiology of the pneumonia was determined either by organism identification or by indirect immunofluorescence in only 139 cases (51%). The most frequently isolated etiological agents were Streptococcus pneumoniae (34 cases), Legionella pneumophila (29 cases) and Mycoplasma pneumoniae (24 cases). The majority of patients with legionellosis were male (79%), middle aged (mean age: 53 years), and living in urban areas (69%). Their clinical features were atypical and did not differ from those of other pneumonias. Four patients with legionellosis (13.8%) died. L. pneumophila was isolated directly in only three instances. The study confirms the high prevalence of legionellosis (20%) among pneumonias of identified etiology. The fact that these cases had an atypical clinical presentation and that isolation of the organism was difficult reinforce the need to apply the CDC criteria for the interpretation of positive serological titers.

[Influenza vaccination and asthma]. / Vaccination antigrippale et asthme.

A double investigation was carried out on the respiratory tolerance of IV in the asthmatic patient: 1. Retrospective based on case history in 87 mature adults (mean age 61 years) previously vaccinated once or several times. This showed poor respiratory tolerance in 21 patients (24%), as shown by difficulty in breathing (8 cases), paroxystic dyspnea (5 cases), an acute episode of asthma (8 cases), occurring soon after vaccination. 2. Clinical and respiratory functional prospective study of bronchial reactivity to carbachol (CBL) and flow-volume curves before and after administration of inactivated polyvalent vaccine, compared in 8 control subjects, 12 asthmatic patients, 19 cases of non-spactic chronic obstructive airway disease, 7 patients with sequelae of pulmonary tuberculosis or operated bronchial cancer, investigated immediately before (day 0), 2, 6, 8 or in some cases 20 or 30 days after IV (D2, D6, D8, D20, D30): 2 of 8 controls showed a decrease in CBL sensitivity threshold at D2 or D6; 6 of 12 asthmatics reacted to the vaccine: 2 showed increased CBL reactivity, 1 lowered sensitivity threshold, 2 a decrease in the 50% and 25% flows at D2 and D6, 1 decreased MMFR and distal flows at D2; 4 of 19 cases of COPD, 1 of 7 cases of tuberculous sequelae showed various reactions at D2, D6, D8.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary lipogranulomatosis due to excessive consumption of apples.

A 55-year-old man was admitted for treatment of unstable angina. Chest x-ray films showed a micronodular pattern, but there were no respiratory symptoms. Autopsy, carried out following sudden death, revealed pulmonary granulomas surrounding lipid crystals. The same crystals were found elsewhere: lymph nodes, spleen, liver, adrenal glands, and were composed of aliphatic hydrocarbons of vegetal origin, mainly C29H60. Investigation of the case history revealed excessive consumption of apples, to which the hydrocarbon deposition could be attributed, since C29H60 is a natural constituent of the cuticular wax in apple peel. This is a unique example of pulmonary granulomatosis due to storage of vegetal hydrocarbons of dietary origin.

[Desensitization technics]. / Techniques de désensibilisation.

Desensitization or immunotherapy (ITS) is a fundamental treatment aimed at the specific allergic component of atopic asthma. The objective of treatment is to prevent antibody-antigen interactions which are generators, among others, of bronchoconstriction. The indications are essentially limited to those asthmatics sufficiently disabled (but without complications nor on long term corticosteroids or other medications in young subjects) with asthma linked to natural lung allergens whose elimination is impossible (domestic dust, mites, pollens, epithelial debris). Proceeding with intermittent repeated injections of extracts of antigen duly identified as responsible, either aqueous products or slow release preparations absorbed as an adjuvant, which allow longer periods between injections and a better clinical tolerance. Some modified extracts are suggested with the aim of reducing allergenicity while maintaining immunogenic potency. Fundamental progress has been made in the 80's is in the purification of allergens and above all in their standardization, controlling the power and the reproducibility of their effects, their duration of action and allowing an objective assessment of the efficacy of ITS in double blind multi-centre trials. The techniques themselves depend on the aqueous choice of or slow release preparation and always consists of a two stage protocol: First, induction by increasing dosage, differentiated in its duration between the traditionally slow method to achieve a maximum ceiling dose in 3 or 4 months, or of only 2 to 4 days, by the rapid or rushed method: secondly repeated maintenance doses, the top dose being chosen to maintain efficacy over several years with a regular rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

[Double-blind study of Biostim in the prevention of superinfection in patients with chronic bronchopathy]. / Etude en double aveugle du Biostim dans la prévention des surinfections des patiènts atteints de bronchopathie chronique.

In a multicenter trial conducted with patients suffering from chronic bronchopathy, Biostim, an immunomodulating compound of biological origin has been studied using the double-blind placebo-controlled method for prevention of respiratory tract infections. One hundred and ten patients from 10 french pneumology health centers entered the study. The treatment was administered at random in three sequences of 8 days a month for 3 months (2 mg/day the first month, 1 mg/day the second and third months). Patients were separated into 2 groups regarding severity of the disease: group I (non complicated chronic bronchitis); group II (obstructive chronic bronchitis with or without respiratory failure). Patients were examined during 6 months with a monthly appraisal of number, duration and treatment clinically defined infectious episodes. The study of propensity to infections with respect to severity of the disease in patients given placebo showed a significantly lower number of infectious episodes in group I when compared to group II. In the group I (patients suffering from simple chronic bronchitis), no significant difference could be noted between placebo and Biostim but, at all events, the low frequency of episodes makes it difficult to evidence a protective effect in such a group. In contrast, with patients presenting a high infectious risk (group II), one can observe in Biostim treated patients compared with placebo group a significant decrease of infectious episodes and a larger number of patients standing free of episodes throughout the whole period of trial. Tolerance to Biostim has revealed itself satisfactory.

[Cardiac tolerance of a beta-2-sympathomimetic spray: fenoterol. Apropos of 37 patients followed using a Holter monitor during a brief treatment protocol]. / Tolérance cardiaque d'un bêta 2-sympathomimétique en spray: le Fénotérol. A propos de 37 sujets suivis par holter en protocole thérapeutique bref.

37 subjects with stable asthma and a mean age of 50.3 undertook a protocol to study the cardiac tolerance to a spray B2SM. A Holter monitor was performed before and 48 hours after the institution of a Fenoterol spray in 4 daily doses of 600 micrograms at fixed times. Before starting treatment with a beta 2 sympathomimetic spray (B2SM) 11 subjects had abnormal traces with significant auricular extra-systoles in 4, ventricular extra-systoles in 5 and both in one subject: one patient had a run of ventricular tachycardia without symptoms. On Fenoterol, a worsening of pre-existing extra systoles was noted thrice, one was auricular the other two ventricular. Two patients had brief runs of ventricular tachycardia but the role of Fenoterol was uncertain; one of the patients was very elderly and hypoxaemic. In the second and elevated theophylline level of 20 micrograms/l was noted. The arrythmogenic power of a B2SM seems weak, but in certain situations such as hypoxaemia, metabolic acidosis and overdosage of theophylline, over consumption of B2SM in association with the above factors could contribute to serious arrhythmias. Also in this study in which there was a protocol limited in time, no premature conclusion should be made on the crucial problem of the cardiovascular risks of B2SM in the basic treatment of asthma but raises the problem of the arrythmogenic potential of the drug association of Theophylline + B2SM.

[Thromboembolic disease in pneumology. Value of mercury-gauge plethysmography with venous occlusion]. / La maladie thrombo-embolique en pneumologie. Apport de la pléthysmographie à jauge de mercure avec occlusion veineuse.

Mercury gauge plethysmography with venous occlusion (PJC) is an atraumatic procedure for the diagnosis of deep venous thrombosis (TVP) of the lower limbs: 103 patients were studied both by plethysmography and phlebography (the reference examination). 54 were hospitalised for a suspicion of pulmonary emboli (EP), 21 for clinical phlebitis and finally 28 subjects had the studies as part of a systematic work-up. 60 cases of TVP of the lower limbs were discovered: 47 were recent, 34 were proximal and 13 sural. The clinical examination failed to reveal these in 36% of cases; the phlebographic and PJC results were concordant for 75% of cases: PJC seemed particularly to be the technique of high sensibility for the early diagnosis of proximal TVP but of a lesser interest for the early diagnosis of peripheral TVP (sensibility 69%). This examination makes an important contribution: for the early diagnosis of hidden proximal TVP; for the diagnosis of EP in its deceptive forms where the presence of a peripheral embolic focus constitutes one weighing factor towards the diagnosis of peripheral thrombo-embolic disease (MIE); for the control of anti-coagulant therapy in the clinic where the local inflammatory process and the biology controlling the consumption of heparin are jointly observed and the study of venous drainage allows an appropriate decision to be made as to the cessation of anticoagulant therapy and minimises the risk of recurrence or avoiding postphlebitis disease by a prolonged treatment.

[Castleman's tumor with thoracic localization. Apropos of a case]. / Tumeur de Castleman à localisation thoracique. A propos d'une observation.

Castleman tumor usually presents as a mediastinal tumor which is never accurately diagnosed before surgery. Pathological findings and postoperative course establish the benign nature of this tumor. However, plasmocytic forms with prominent hematologic manifestations may be difficult to distinguish from a malignant lymphoma or thymoma. Differential diagnosis is all the more important that no complementary postoperative treatment is indicated in benign lymphoid tumors.

[Cytology and phospholipid content of the bronchoalveolar lavage liquid in diffuse interstitial pneumopathies and in sarcoidosis. Apropos of 96 lavages]. / Etude cytologique et phospholipidique du liquide de lavage broncho-alvéolaire au cours des pneumopathies interstitielles diffuses et des sarcoïdoses. A propos de 96 lavages.

The phospholipid content of bronchoalveolar lavage (LBA) has been little studied till now. This work involved 96 LBA on 7 cases of allergic alveolitis, 11 cases of diffuse interstitial fibrosis (FID) and 42 of sarcoidosis. The liquid collected was submitted to a cellular study (cellularity, total and differential) and biochemical (total proteins, total phospholipids separated into their different fractions by chromatography which enabled the identification of phosphatidyl-choline, phosphatidyl-serine and phosphatidyl-inositol in particular). The cytological results were close to the classical data, a rise in the lymphocyte level in allergic alveolitis and active sarcoid, a rise in polymorphonuclear cells in FID. Biochemical analysis showed a fall in total phospholipids for the whole group, the drop being the greatest in the FID. Phosphatidyl-choline, the principle phospholipid of surfactant in normals, was reduced in all three groups of patient when expressed as a percentage of total phospholipids. This fall was greatest with an allergic alveolitis and occurred on a pro rata basis with a rise in phosphatidyl-serine and inositol. The protein phospholipid ratio (PL/P) expressed in micrograms of phospholipid and milligrams of protein fell in a significant fashion in all the pathological groups. This fall was significantly larger in allergic alveolitis than FID and active sarcoid. The PL/P ratio seems to be a good marker of active sarcoid, correlating with the activity of the disease inversely with the lymphocyte level, and was unchanged by steroids unlike the lymphocyte count. A rise in this ratio correlates with an improvement in the radiological and clinical state.

[Noxytioline in the local treatment of empyema (author's transl)]. / La noxytioline dans le traitement local des épanchements pleuraux purulents.

The importance assumed by local treatment in non-tuberculous purulent pleurisy has suggested that intrapleural applications of a broad spectrum antiseptic could be as useful as in peritonitis. Fifteen adult patients with empyema secondary, in most cases, to local, usually Gram-negative, infections were treated with combined antibiotic therapy and locally administered noxytioline. The patients underwent 3 to 30 intrapleural lavages (average 9) via a pleurotomy drainage tube (11 cases) or after pleural puncture (4 cases). Results were very satisfactory in 12 out of 15 cases, with mild pleural sequelae in 8 cases. No local or systemic reactions were observed. This treatment proved particularly effective in 5 difficult cases.