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International audience; The neurotensin receptor-3 also known as sortilin was the first member of the small family of vacuolar protein sorting 10 protein domain (Vps10p) discovered two decades ago in the human brain. The expression of sortilin is not confined to the nervous system but sortilin is ubiquitouslyexpressed in many tissues. Sortilin has multiple roles in the cell as a receptor or a co-receptor, in protein transport of many interacting partners to the plasma membrane, to the endocytic pathway and to the lysosomes for protein degradation. Sortilin could be considered as the cells own shuttlesystem. In many human diseases including neurological diseases and cancer, sortilin expression has been shown to be deregulated. In addition, some studies have highlighted that the extracellular domain of sortilin is shedded into the culture media by an unknown mechanism. Sortilin can bereleased in exosomes and appears to control some mechanisms of exosome biogenesis. In lung cancer cells, sortilin can associate with two receptor tyrosine kinase receptors called the TES complex found in exosomes. Exosomes carrying the TES complex can convey a microenvironmentcontrol through the activation of ErbB signaling pathways and the release of angiogenic factors. Deregulation of sortilin function is now emerging to be implicated in four major human diseases - cardiovascular disease, Type 2 diabetes mellitus, Alzheimer disease and cancer.

Introduction La decision therapeutique chez les personnes âgees est delicate en raison de la grande heterogeneite de cette population. Notre objectif etait d’evaluer le role de l’âge dans la prise en charge des patients atteints de cancer primitif du poumon vus dans le service de Pathologie respiratoire du CHU de Limoges entre 2002 et 2004. Methodologie Une etude transversale a analyse la prise en charge de 363 patients atteints d’un cancer bronchique primitif. Les patients inclus etaient divises en deux groupes selon leur âge ( Resultats Les comparaisons en fonction de l’âge mettaient en evidence une alteration de l’autonomie plus marquee, un score de Charlson plus eleve, un recours moindre aux traitements pour la radiotherapie et la chimiotherapie, l’utilisation de traitements symptomatiques plus frequemment chez les plus âges (p Conclusions L’evaluation geriatrique des patients âges atteints d’une neoplasie pulmonaire primitive doit permettre de definir l’âge physiologique du patient et d’adapter la prise en charge afin de leur assurer la meilleure prise en charge tout en leur garantissant la meilleure qualite de vie.

INTRODUCTION: We report two cases occurring in 2004 of patients being treated for pleural mesothelioma with a combination of cisplatin or carboplatin and pemetrexed. Investigation by skin tests and flow cytometry confirmed the clinical diagnosis in both cases. CASE REPORTS: Case 1: a man of 62 developed, after 12 courses of cisplatin-pemetrexed, an anaphylactic reaction 5 minutes after the infusion of cisplatin. Treatment was withdrawn permanently. Case 2: a man of 66 developed, after 7 courses of cisplatin-pemetrexed, an anaphylactic reaction within the first minute of the infusion of cisplatin. Subsequently, in March 2004, he received pemetrexed alone without any problems. In August 2004 he was prescribed carboplatin-pemetrexed. Within 5 minutes he developed urticaria, pruritus and abdominal pain. He was treated later with pemetrexed alone with no problems. CONCLUSION: Hypersensitivity to platinum salts usually occurs after several courses of treatment. Skin tests and flow cytometry are a simple, concordant, and reliable way of confirming the diagnosis.

Resume L'allergie alimentaire au porc est rare. Cependant, nous en rapportons 13 cas, concernant surtout l'allergie aux rognons. Les reactions peuvent etre severes. Les sensibilisations croisees sont nombreuses avec d'autres mammiferes. Une meilleure connaissance des allergenes en cause est necessaire pour mieux identifier les risques chez ces patients.

Resume Contexte Le plan Hopital 2007 a favorise le developpement de l’hospitalisation a domicile (HAD). L’objectif de ce travail etait de comparer les couts en HAD d’une chimiotherapie dans le cancer du poumon non a petites cellules (CBP NAPC) a la prise en charge habituelle. Methodes 10 patients ont recu le J de leur cycle de chimiotherapie en HAD versus une administration en hopital de jour. L’analyse a porte sur les tarifs d’administration de cette chimiotherapie. Resultats 30 injections dites « classiques » ont ete comparees aux 24 injections en HAD. Le cout d’un cycle classique est de 2 829,51 [2 560,74-3 147,02]. Pour l’HAD le cout par cycle est de 2 372,50 [1 962,75-2 792,88]. Cette difference est de - 457,01 par cycle en faveur de l’HAD [-919,74 ; 26,82]. Le tarif d’une injection en HAD est de 699,89 [643,64 ; 750,23] alors que le cout reel s’eleve a 484,42 [424,18 ; 540,32]. Il n’y a pas plus d’effets secondaires dans le groupe HAD. Conclusion La realisation d’une chimiotherapie en HAD est possible avec un cout inferieur de 16 %. Les resultats de cette etude, non randomisee, doivent etre confirmes dans le cadre d’essais cliniques ulterieurs.

Resume Objectif Parmi les obstetriciens et les sages-femmes, evaluer le pourcentage de fumeurs, apprecier la proportion des soignants qui evoquent le tabagisme lors de la surveillance d'une grossesse, la qualite de l'information apportee aux patientes, ainsi que leur experience en tabacologie. Patientes et methodes L'echantillon de 188 personnes etait constitue des gynecologues–obstetriciens, sages-femmes et eleves sages-femmes du centre hospitalo-universitaire (CHU) et des etablissements prives de Limoges ainsi que des centres hospitaliers generaux du Limousin. Un questionnaire postal leur a ete envoye en fevrier et mars 2002. Resultats Cent quarante-deux reponses ont ete obtenues (taux de reponse 75,5 %). L'âge moyen des repondants etait de 37 ans (20–59 ans) avec un tabagisme actif de 43,6 %. La question du tabagisme pergravidique et de ses risques est abordee par la grande majorite des soignants. Le conseil minimal est connu et prodigue par 34,4 % des gynecologues et 26,5 % des sages-femmes. Soixante-deux pour cent des gynecologues et 79 % des sages femmes n'ont jamais propose a leurs patientes de consultation de tabacologie. Soixante-dix pour cent des personnes interrogees n'ont pas recu de formation specifique en tabacologie durant leurs etudes. Discussion et conclusion La prise en charge du tabagisme pergravidique semble etre insuffisante en milieu gynecologique en Limousin. La formation en tabacologie du personnel obstetrical fait defaut.

Resume Objectif Il s’agissait de montrer la faisabilite de la substitution a domicile par Tegeline® (immunoglobuline humaine normale) d’un point de vue efficacite, securite, tolerance, de valider la pertinence de la selection et de la formation des patients pouvant beneficier de ce mode d’administration, d’en evaluer a long terme l’efficacite et la securite. Methode Cette etude retrospective a ete realisee chez des patients ayant un deficit immunitaire primitif traites auparavant par immunoglobulines (Ig) intraveineuses au moins 6 mois en milieu hospitalier, formes par le Centre de formation au traitement a domicile de l’enfant (CFTDE) et ayant recu au moins une perfusion a domicile de Tegeline® a partir du 1er janvier 2000. Tegeline® contient en moyenne 97,6 % d’IgG entieres (58,8 % d’IgG1, 34,1 % d’IgG2, 5,4 % d’IgG3 et 1,7 % d’IgG4). Resultats Deux cent dix-huit fiches de suivi ont ete completees par 13 patients pour lesquels tous les criteres d’eligibilite etaient reunis. Le nombre total de perfusions par patient a varie de 4 a 41. Aucune difficulte d’administration n’a ete signalee chez 10 patients, des difficultes de pose ont ete notees chez les 3 autres motivant un retour a une prise en charge hospitaliere (apres 6 et 10 mois) dans 2 cas. Le debit de perfusion a ete habituellement de 2 a 3 ml/kg/h. Au cours de la periode de suivi, il n’y a eu aucun episode infectieux chez 5 patients ; 8 ont eu des episodes traites par antibiotiques. D’un point de vue tolerance, les “kits de securite” (corticoides, adrenaline) dont disposait chaque patient n’ont jamais ete utilises. Au long cours, la duree mediane de ces perfusions a domicile se situe a 5 ans et 6 mois. Conclusion Chez des patients prealablement formes et selectionnes, cette etude demontre l’efficacite, la securite et la tolerance de la substitution par Tegeline® a domicile.

Resume La prevalence et la prise en charge de l’allergie alimentaire en milieu scolaire a Limoges ont ete etudiees par un questionnaire. Sept cent quarante-huit reponses sur 1086 ont pu etre analysees. Il en ressort une prevalence de 5,35 % soit 40 declarations. Les principaux aliments en cause appartiennent a la famille des rosacees, a celle des legumineuses (arachide) ou aux aliments du groupe latex. Une polysensibilisation est surtout observee chez les enfants de plus de 10 ans. Quatre chocs anaphylactiques ont ete rapportes, mais 1 seul beneficie d’un projet d’accueil individualise. Malgre d’evidents progres ces dernieres annees, la prise en charge de ces affections reste encore insuffisante.

The success of transplantation of human embryonic mesencephalic tissue to treat parkinsonian patients is limited by the poor survival of the transplant. We show that an AAV2 vector mediates efficient expression of the egfp reporter gene in organotypic cultures of freshly explanted solid fragments of rat embryonic ventral mesencephalon (VM). We observed early and sustained transgene expression (4 days to > or = 6 weeks). Furthermore, rAAV-infected rat embryonic VM transplanted in the adult striatum continued to express EGFP for > or = 3 months. More than 95% of the transduced cells were neurons. Dopaminergic neurons were transduced at low frequency at earlier time points. This method of gene delivery could prove useful to achieve local, continuous secretion of neurotrophic factors at physiologically relevant doses to treat Parkinson's disease.

International audience; The transfer of exosomes containing both genetic and protein materials is necessary for the control of the cancer cell microenvironment to promote tumor angiogenesis. The nature and function of proteins found in the exosomal cargo, and the mechanism of their action in membrane transport and related signaling events are not clearly understood. In this study, we demonstrate, in human lung cancer A549 cells, that the exosome release mechanism is closely linked to the multifaceted receptor sortilin (also called neurotensin receptor 3). Sortilin is already known to be important for cancer cell function. Here, we report for the first time its role in the assembly of a tyrosine kinase complex and subsequent exosome release. This new complex (termed the TES complex) is found in exosomes and results in the linkage of the two tyrosine kinase receptors TrkB (also known as NTRK2) and EGFR with sortilin. Using in vitro models, we demonstrate that this sortilin-containing complex exhibits a control on endothelial cells and angiogenesis activation through exosome transfer.

A Phase I trial of carboplatin therapy was performed on patients with locally advanced non-small cell lung cancer who had been previously treated with cisplatin, mitomycin and a vinca alkaloid. This was administered as a daily bolus infusion or as a continuous infusion for 6 weeks with concurrent daily thoracic radiation. All patients had to be objective responders or to show no change after chemotherapy. The carboplatin was started at 10 mg/m 2 per day, and increased to 15 mg/m 2 per day and 20 mg/m 2 per day, if treatment was feasible in successive cohorts of at least six patients. The radiation therapy consisted of 62–66 Gray on the tumor and the ipsilateral mediastinal nodes, 50 Gray on the mediastinum and 40–45 Gray on the supraclavicular lymph nodes. Twenty-nine patients took part in this study. Thrombocytopenia was the principal dose-limiting toxicity, with 15 mg/m 2 per day of bolus or continuous infusion. Other toxicities included a fall in haemoglobin level, a fall in white-blood cell count, nausea and vomiting. The median survival time is 12 months, but the response rate cannot be determined among patients selected on the basis of response to chemotherapy. The recommended Phase II dose for patients previously treated with cisplatin containing chemotherapy, is 10 mg/m 2 per day of either a bolus or continuous infusion.

The aim of this study was to assess the percentage of respiratory disorders and airway obstruction in patients with rheumatoid arthritis by comparing lung function test results between patients with rheumatoid arthritis and control subjects with other rheumatological conditions. A prospective case-control study of respiratory symptoms and lung function abnormalities was performed in a series of 100 patients with rheumatoid arthritis. Eighty eight patients with other rheumatological diseases served as controls. Diagnosis of respiratory disorders was based on clinical, radiological and spirometric findings. Airway obstruction was determined from predicted values. The results were compared using Student's t-test and Chi-squared tests. An explanatory analysis was carried out by linear regression. The number of symptoms, respiratory disorders (including bronchiectasis) and lung function abnormalities was higher in patients with rheumatoid arthritis than in controls. After exclusion of smokers, the proportion of airway obstruction in patients with rheumatoid arthritis was 16% (versus 0% in controls), although the patients with rheumatoid arthritis still had more symptoms and respiratory disorders. The Chi-squared test did not identify any relationship between airway obstruction, duration of rheumatoid arthritis and type of treatment and occurrence of Sjogren's syndrome. In the nonsmokers, different explanatory models for the patients with and without a history of cardiac and respiratory disease emerged from multivariate analysis of indices of obstruction. These models included variables characterizing the severity and course of the rheumatoid arthritis. Respiratory disorders (including bronchiectasis) and airway obstruction are more frequent among patients with rheumatoid arthritis than in rheumatological controls. Although the exact pathophysiology of the link between bronchial obstruction and rheumatoid arthritis is still a matter of debate, explanatory factors for obstruction included variables characterizing the rheumatoid arthritis.

Neural stem cells (NSCs) are slowly dividing astrocytes that are intimately associated with capillary endothelial cells in the subventricular zone (SVZ) of the brain. Functionally, members of the vascular endothelial growth factor (VEGF) family can stimulate neurogenesis as well as angiogenesis, but it has been unclear whether they act directly via VEGF receptors (VEGFRs) expressed by neural cells, or indirectly via the release of growth factors from angiogenic capillaries. Here, we show that VEGFR-3, a receptor required for lymphangiogenesis, is expressed by NSCs and is directly required for neurogenesis. Vegfr3::YFP reporter mice show VEGFR-3 expression in multipotent NSCs, which are capable of self-renewal and are activated by the VEGFR-3 ligand VEGF-C in vitro. Overexpression of VEGF-C stimulates VEGFR-3-expressing NSCs and neurogenesis in the SVZ without affecting angiogenesis. Conversely, conditional deletion of Vegfr3 in neural cells, inducible deletion in subventricular astrocytes, and blocking of VEGFR-3 signaling with antibodies reduce SVZ neurogenesis. Therefore, VEGF-C/VEGFR-3 signaling acts directly on NSCs and regulates adult neurogenesis, opening potential approaches for treatment of neurodegenerative diseases.

Described by Reich and Johnson in 1992 [2], the Lady Windermere syndrome occurs exclusively in non-smoking women over the age of 60 years, without significant pre-existing pulmonary disease. It comprises bronchial dilatation, typically in the middle lobe and lingula, together with secondary infection by atypical mycobacteria (Mycobacterium avium in the first cases). Among the 17 cases of atypical mycobacterial infection that we have seen in the past 14 years, there were seven cases of this syndrome. It was associated with cough, sputum, sometimes haemoptysis, febrile episodes and deterioration of general health. The diagnostic criteria and treatment were defined by the American Thoracic Society. The pathophysiological hypothesis proposed by Reich and Johnson was that voluntary suppression of the cough led to congestion of the bronchi and secondary infection with atypical mycobacteria. Currently it is thought more likely that the following factors are involved: progressive increase in dilatation of small bronchi, delayed diagnosis, morphological abnormalities of the thorax, hormonal factors, immune deficiency, genetic neutrophil dysfunction, and even heterozygous forms of cystic fibrosis.

Resume Dans une etude ouverte, randomisee et multicentrique conduite en medecine liberale, cinquante medecins generalistes ont assure le recrutement prospectif de 356 patients presentant un episode de surinfection de broncho-pneumopathie chronique obstructive. Cent soixante-quatorze ont ete repartis dans un groupe de traitement par le cefadroxil, 2 g par jour en deux prises quotidiennes; et 182 autres patients ont recu l'association amoxicilline — acide clavulanique, 1,5 g par jour en trois prises quotidiennes. La duree de traitement etait de 10 j. Sur 333 patients analysables, l'analyse de l'efficacite clinique a montre qu'il n'existait pas de difference significative entre les deux groupes de traitement en terme d'evolution des symptomes de J1 a J10, et de leur presence a J10. Treize patients (7,5%) dans le groupe cefadroxil et 49 (27%) dans le groupe amoxicilline — acide clavulanique ont presente au moins un effet indesirable. La tolerance clinique globale a ete jugee bonne chez 92,5% des patients dans le groupe cefadroxil et 72,3% dans le groupe amoxicilline — acide clavulanique, cette difference etait hautement significative (p = 10−4). L'efficacite clinique du cefadroxil comparable a celle de l'association amoxicilline — acide clavulanique, et sa meilleure tolerance observee au cours de cette etude, suggerent que le cefadroxil est un antibiotique adapte au traitement des surinfections de BPCO.

Resume Un essai multicentrique, ouvert, randomise sur 2 groupes paralleles de traitement a ete realise en medecine communautaire dans le but de comparer l'efficacite clinique et la tolerance du cefadroxil administre a la posologie de 2 g/j et de l'association amoxicilline-acide clavulanique 1,5 g/j, dans le traitement par voie orale des pneumopathies aigues de l'adulte presumees a pneumocoque, sur des criteres cliniques et radiologiques. Les patients etaient revus au 4e jour du traitement puis a la fin de celui-ci, au douzieme jour ± 2. Une visite facultative avait lieu vers le 30e jour de l'essai. Sur les 87 patients inclus dans l'etude, 75 etaient analysables pour l'evaluation de l'efficacite a J12. Les 2 groupes de traitement etaient homogenes a l'inclusion sur l'ensemble des parametres cliniques et demographiques etudies. L'evolution de la symptomatologie etait comparable dans les 2 groupes ; mais la tolerance clinique s'est revelee statistiquement meilleure dans le groupe cefadroxil, le pourcentage de patients ayant presente au moins un effet indesirable etant de 5 % dans ce groupe, versus 26 % dans le groupe oppose, la survenue d'effets indesirables digestifs ayant entraine la sortie d'essai de 3 patients. Dans le traitement de premiere intention des pneumopathies aigues de l'adulte presumees a pneumocoque, le cefadroxil et l'association amoxicilline — acide clavulanique sont apparus avoir une efficacite comparable.

Pirarubicin (THP) (Roger Bellon Laboratory, France) is a new anthracycline under clinical development. In order to assess the efficacy and toxicity of the drug in small-cell lung carcinoma (SCLC), we have undertaken this trial in front-line therapy in patients with metastatic disease, PS less than 3 and at least one evaluable lesion. Responses were assessed after two cycles of THP (60 mg/m2 i.v. bolus every 3-4 weeks) and a further cross over to VP16 + CDDP (three cycles) was systematic whatever the response to THP. This crossover was performed after only one cycle in case of obvious progression. From June 1988 to April 1990, 32 patients were enrolled: 6 were ineligible (4 non-SCLC, 2 M0), 26 patients were fully evaluable for THP and 18 patients for VP16-CDDP. The characteristics of the patients were as follows: mean age 57.4 years (38-71); T4: 54%; T3: 27%; T2: 19%; N3: 62%; N2: 35%; No: 4%. The efficacy was as follows 1 complete response and 2 partial responses (confirmed by endoscopy); 12 patients received only one cycle because of obvious progression; the overall response rate is 12% (95% confidence interval 0-24%). The patient who had complete response after pirarubicin remained in CR after VP16-CDDP, whereas the 2 patients who had partial response achieved CR for one and PR for the other; among the 15 who did not respond 1 CR and 7 PR were observed. The only significant toxicity of THP was granulopenia without infection. THP seems to be an effective anthracycline in SCLC, and the study is continuing. A response could be reached in 50% of the nonresponders with standard therapy and 10 of 24 patients (42%) finally responded. Therefore, this schedule for testing new drugs in metastatic SCLC appears ethically acceptable.

International audience

Multidrug-resistant tuberculosis (MDR-TB), defined by resistance to both isoniazid and rifampin, is an increasing problem that accounts for 400,000 new cases worldwide each year [1]. The prognosis of individuals infected with MDR-TB remains poor, with 10–30% of cases resulting in failure and death [2]. Fluoroquinolones are some of the few potent antibiotics still active against most MDR strains of M. tuberculosis, and their use has been identified as a favorable prognostic factor in cases of MDR-TB [3]. Recently, the emergence of extensively drug-resistant strains (XDR) has been reported and these strains have been associated with a worse prognosis than MDR-TB strains [2]. XDR-TB is an infection with a MDR strain that is resistant to any fluoroquinolone and at least one of the three injectable drugs (capreomycin, kanamycin or amikacin) [4]. We describe here a clinical case of XDR-TB that illustrates the critical role fluoroquinolones play in the management of drugresistant tuberculosis. The case involved a 51-year-old man with no comorbid conditions who had been treated in Algeria for pulmonary tuberculosis since June 2001. The initial antibiotic susceptibility profile of the causative strain was unknown. His original treatment, which included isoniazid, rifampin, ethambutol and pyrazinamide for 3 months followed by isoniazid and ethambutol, had been taken irregularly. When hospitalized in Limoges, France, in June 2002, he suffered fever, anorexia, weight loss (15 kg), cough and hemoptysis. A computed tomography scan showed bilateral cavitations of the upper lobes (Fig. 1). Sputum-smear examination detected abundant acid-fast bacilli. Treatment with rifampin, isoniazid and pyrazinamide was initiated. Culture grew M. tuberculosis. Susceptibility testing of first-line drugs revealed resistance to rifampin, isoniazid, pyrazinamide and streptomycin. Treatment was consequently switched to amikacin (750 mg/day), ofloxacin (800 mg/day), ethionamide (500 mg/day) and ethambutol (1 g/day). Molecular studies performed at the National Reference Center revealed mutations in the katG gene (S315T), rpoB gene (H526D) and pncA gene (T100P), but no mutation in the gyrA gene [5, 6]. Further drug susceptibility tests showed resistance to isoniazid, rifampin, pyrazinamide, streptomycin, ethambutol, kanamycin, ethionamide, thiacetazone and cycloserine. The strain remained susceptible to amikacin, capreomycin, fluoroquinolones and para aminosalicylic acid. As a result, treatment was switched to amikacin (750 mg/day), ofloxacin (800 mg/day) and PAS (10 g/day) for 4 months. Under this treatment the patient’s general condition improved. In January 2003, treatment was continued with the combination of moxifloxacin (400 mg/day) and PAS and maintained for 12 more months. However, in May 2003 the patient returned to Algeria, where he again took his medication irregularly. In March 2004, he was readmitted Eur J Clin Microbiol Infect Dis (2007) 26:423–425 DOI 10.1007/s10096-007-0298-0

We report two cases occurring in 2004 of patients being treated for pleural mesothelioma with a combination of cisplatin or carboplatin and pemetrexed. Investigation by skin tests and flow cytometry confirmed the clinical diagnosis in both cases.Case 1: a man of 62 developed, after 12 courses of cisplatin-pemetrexed, an anaphylactic reaction 5 minutes after the infusion of cisplatin. Treatment was withdrawn permanently. Case 2: a man of 66 developed, after 7 courses of cisplatin-pemetrexed, an anaphylactic reaction within the first minute of the infusion of cisplatin. Subsequently, in March 2004, he received pemetrexed alone without any problems. In August 2004 he was prescribed carboplatin-pemetrexed. Within 5 minutes he developed urticaria, pruritus and abdominal pain. He was treated later with pemetrexed alone with no problems.Hypersensitivity to platinum salts usually occurs after several courses of treatment. Skin tests and flow cytometry are a simple, concordant, and reliable way of confirming the diagnosis.

The transfer of exosomes containing both genetic and protein materials is necessary for the control of cancer cell microenvironment to promote tumor angiogenesis. The nature and function of proteins found in the exosomal cargo, their mechanisms in membrane transport and related signaling events are not clearly understood. The multifaceted receptor, neurotensin (NT) receptor-3, also called sortilin plays a multitude of roles in the cell as a receptor or a co-receptor, in protein transport to the plasma membrane and to lysosomes, and in the regulated secretion. Numerous studies indicate that sortilin expression is elevated in several human cancers. These same reports suggested that NT mediated by sortilin stimulated by an autocrine/paracrine function could be a mechanism associated with the tumorigenesis. In this study, we demonstrate in human lung cancer A549 cells, that the exosome release mechanism is closely linked to a multifaceted receptor, neurotensin (NT) receptor-3 also called sortilin. Sortilin is already known to be important for cancer cell function. We report for the first time its role in the assembly of a tyrosine kinase complex and subsequent exosome release. This novel complex (TES complex) found in exosomes results in the linkage of two tyrosine kinase receptors, TrkB and EGFR with sortilin. Using in vitro models, we demonstrate that this complex containing sortilin exhibits a control on endothelial cells and angiogenesis activation through exosome transfer. We show for the first time, a new role for sortilin in the release and the assembly TES complex in lung cancer cells. Our data suggest a paracrine function for sortilin and its partners in exosome transfer and the control of the microenvironment. This novel complex containing sortilin could act as a molecular switch in cancer progression by promoting angiogenesis.

Sclerosing epithelioid fibrosarcoma is a rare tumor recently described. The histological presentation can be confused with certain soft tissue benign tumors and certain sarcomas. Metastatic spread is usually late in the natural course of the disease. We report a case of recurrent sclerosing epithelioid fibrosarcoma with pleural metastases which developed ten years after surgical resection of the primary tumor. The tumor was formed by small uniform round epithelioid cells with a clear cytoplasm. The tumor cells were strongly positive for vimentin. This clinical case is discussed in light of other cases reported in the literature.

French law and government decisions have induced new development for home base treatments. The objective was to compare cost of home base chemotherapy (HBC) versus outpatient infusions, for non small cell lung cancer (NSCLC).10 patients were selected in each category. D8 of their cycles was performed at home compared to outpatient infusion. Costs were based on national fees with cytostatic drugs as supplement. The real cost was also assessed through a specific questionnaire.30 D8 infusions were carried out at hospital and 24 D8 infusions at home. Average cost by cycle was 2,829.51 euros [2 560.74-3 147.02] for hospital infusion, 2,372.50 euros [1 962.75-2 792.88] for HBC (-16.15%). Difference was -457.01 euros by cycle [-919.74; 26.82]. Real costs by injection for BHC was 484.42 euros [424.18; 540.32] versus a fee of 699.89 euros [643.64; 750.23]. There were no difference in terms of adverse events.HBC for NSCLC is feasible. Average costs by cycle is lower of 16% versus hospital infusion. The results of this non randomized study had to be confirm by further clinical trials.

According to physician, Aspirin and NSAIDS hypersensitivity are causing three major problems: how to make the diagnosis? Which treatment are to he given to these patients? What kind of anti-inflammatory drugs are to be prescribed? For these last three years, several articles regarding these matters were being published.

The purpose of this study was to evaluate the performance of 18 F-fluorodeoxyglucose ( 18 FDG) imaging via coincidence detection emission tomography (CDET) in identifying malignant lesions in subjects exposed to asbestos. A total of 30 patients exposed to asbestos underwent 18 FDG-CDET between January 2000 and June 2003. A CDET scan of the thorax and abdomen was performed 60 min after injection of 18 FDG in fasting patients, and results were obtained in slices in three axes. The CDET results were compared to those from computed tomography (CT), and pleural or surgical biopsy in patients with positive 18 FDG-CDET results. All primary malignant mesotheliomas accumulated 18 FDG (n=6), and, in two patients, CDET findings were superior to those of CT, allowing early detection. In two cases, lung carcinomas with malignant pleural effusion were also detected. There were five false positive CDET results: three unilateral pleural thickening, one rounded atelectasis, and one benign lung nodule. All patients with pleural plaques showed no significant 18 FDG uptake. Malignant diseases were detected by 18 FDG-CDET imaging with a sensitivity of 89% and specificity of 71%. Coincidence detection emission tomography can identify malignant mesothelioma in selected subjects exposed to asbestos. Coincidence detection emission tomography appears to be a useful noninvasive method for the follow-up of subjects with exposure risk of asbestosis.

To demonstrate the feasibility of administration Tegeline at home from a point of view of efficacy, safety, tolerance, to validate the pertinence of the selection and the training of patients who could benefit from this type of administration and to assess the long term efficacy and safety.This retrospective study was conducted in patients exhibiting primary immune deficiency and formerly treated with intravenous immunoglobulins at least six months in hospital settings, trained by the centre for the training of children in the home (Centre de formation au traitement à domicile de l'enfant--CFTDE) and having received at least one administration of Tegeline at home from January 1st 2000. Tegeline contains a mean of 97.6% of whole IgG (58.8% of IgG1, 34.1% of IgG2, 5.4% of IgG3 and 1.7% of IgG4).Two hundred and eighteen follow-up sheets were completed by 13 patients in whom all the eligibility criteria were fulfilled. The total number of infusions per patient ranged from 4 to 41. No difficulty in administration was reported in 10 patients, difficulties in placing the needle were encountered in 3 other patients and motivating their return to the hospital for treatment (after 6 and 10 months) in 2 cases. The infusion flow rate was usually of 2 to 3 ml/kg/h. During the follow-up period, no episode of infection was noted in 5 patients and 8 presented infections that were treated with antibiotics. Regarding safety, the security 'kits' (corticosteroids, adrenalin) that were supplied to each patient were never used. Over time, the median duration of the infusions at home was of 5 years and 6 months.In trained and selected patients, this study demonstrated the efficacy, safety and tolerance to the administration of Tegeline at home.

107 patients have discontinued Hymenoptera venom immunotherapy between 1988 and 2000. 31 have been seen again with intradermal tests with IgEs, and 81 responded to a questionnaire. Intradermal reactions and IgEs decrease together significantly during immunotherapy and then persist at low level during three years. Beyond, the number of patients is insufficient. 32 patients were stung by the same Hymenoptera and not had any systemic reaction. However, five have beta blockers, three have IEC and half of the patients don't take precautions to avoid Hymenoptera.

Risperidone is an atypical neuroleptic which has been incriminated as a cause of respiratory symptoms. The purpose of this prospective study was to assess over a three-month period the respiratory status of patients free of allergic or respiratory disease treated with risperidone. Thirty-nine patients were enrolled. Twenty dropped out. One patient developed cough very likely related to risperidone but with no change in function. Bronchial hyperreactivity developed in two other patients who had no clinical symptom or sign of respiratory disorder. Despite the small number of patients in this study, risperidone would appear to have secondary respiratory effects. The high frequency of bronchial hyperreactivity observed in patients at inclusin and the nearly constant co-prescription of other psychiatric drugs suggests a potential combination effect (notably with selective seritonin reuptake inhibitors).

Although asthma is the most common pulmonary condition in pediatrics, the incidence of exercise-induced asthma (EIA) in school children is not well documented and few studies have been devoted to the condition. There are considerable variations in morbidity and mortality between countries. This study was designed to evaluate the prevalence of EIA in children in the 6th grade (11-14 year-olds) in one French department (Haute-Vienne) and to identify undiagnosed cases.The representative sample was obtained over a period of 28 days (February 2(nd) to April 10(th) 1998) by cluster sampling method, stratified by size of the schools. The number of subjects planned was 891. The selected children filled in a questionnaire on their asthma history and were subjected to an outdoor exercise test (6 minute run). Respiratory function was measured with a peak flow-meter.Seven hundred and eighty two school children were included in this survey. Participation rate was 87.8%. The prevalence of asthma from the questionnaire was 10.7% (CI 95%: 8.7 - 12.8). After exercise, 68 school children presented exercise-induced bronchospasm: the prevalence of the EIA was 8.7% (CI 95%: 6.9 - 10.5). Among these 68 school children, 27 were known asthmatics and 41 were not. With the 10 treated asthmatics, the overall prevalence of EIA was therefore estimated at 9.9% (CI 95%: 8.2 - 11.7).The prevalence of asthma and EIA was close to that found in other studies using a similar methodology. EIA remains under-diagnosed since 41 undeclared asthmatic school children were identified in our population. Nurses'information is necessary to initiate the use of systematically testing respiratory function (with a peak flow meter) at least once a year. Efficient management of the asthmatic child requires cooperation between the various professionals dealing with school children.

Gemcitabine is used to treat solid tumours such as non small-cell lung cancer. In general, it is a well tolerated cytotoxic agent and myelosuppression is the major dose limiting side-effect. Pulmonary toxicity has been described and dyspnoea occurs in approximately 8% of patients in whom, for the majority, it is mild and reversible. But several cases of acute respiratory distress syndrome (ARDS) related to Gemcitabine treatment have been reported since 1997 and a few were fatal. We present a case of Gemcitabine toxicity in a patient treated for a lung cancer. He presented with a respiratory distress syndrome due to acute interstitial pneumonitis from which he promptly recovered with corticosteroid therapy.

The purpose of this study was to investigate the utility of 18fluorodeoxyglucose (FDG) coincidence detection position emission tomography (CDET) in the evaluation of metastatic mediastinal lymph nodes in patients with potentially operable non-small-cell lung cancer (NSCLC). A prospective study was performed in thirty patients with newly suspected NSCLC. Thoracic computed tomography (CT), FDG CDET, and invasive surgical staging were performed in patients. Blinded prospective interpretation was performed for each test and compared to pathological staging obtained by mediastinoscopy and/or by thoracotomy. Patients were followed for six months to detect occult metastases. The sensitivity and specificity of CDET for the detection of mediaStinal lymph nodes were 75% and 94.4% respectively. The corresponding value for CT were 50% and 80.9%. Three patients with N1 disease were classified as N0 by CDET. With regard to definitive surgical node staging, CDET could identify nodal disease in 26 patients and CT only in 18 patients (n = 30). FDG full-ring positron emission tomography (PET) is the most accurate non-invasive method for the detection and staging of lung cancer. In addition, FDG CDET shows high accuracy for the detectability of pulmonary lesions with a diameter at least 2 cm and the evaluation of lymph node in NSCLC.

Chronic obstructive bronchiolitis with organizing lung disease is an anatomoradioclinical entity characterized by nonspecific inflammation associated with recurrent migratory minimally dense alveolar opacities on the chest x-ray poorly responsive to corticosteroid therapy. Excepting this typical presentation, other clinical forms may occur. We report the cases of two patients with an exceptional localized presentation raising the differential diagnosis of lung cancer.

Renal metastasis from carcinoma of the lung is rarely a clinical problem. Autopsic series however prove that the kidney is a frequent metastatic organ (20%). We report the case of a 43-years-old male patient affected with a squamous cell carcinoma of the lung, with bilateral renal extension. These secondary localizations were detected through a left flank pain prior to a systemic inflammatory response syndrome. The absence of hematuria (even microscopic) contrasted with the importance of the lesions. The age, along with the poor general state of our patient and the absence of any CT specificity justified an exploratory lobotomy. The pathologic analysis of the renal biopsies confirmed the metastatic nature of the lesion.

Thoracic infection by anaerobes are uncommon diseases and often presents difficulty in diagnosis. We report a case of thoracic infection due to Fusobacterium Nucleatum. A 60-year old man presented a lesion infiltrating from the lung to the thoracic wall. Fusobacterium Nucleatum was isolated on pus collected. Treatment by penicillin, metronidazole combined with surgical drainage was highly effective.

A Phase I trial of carboplatin therapy was performed on patients with locally advanced non-small cell lung cancer who had been previously treated with cisplatin, mitomycin and a vinca aklaloïd. This was administered as a daily bolus infusion or as a continuous infusion for 6 weeks with concurrent daily thoracic radiation. All patients had to be objective responders or to show no change after chemotherapy. The carboplatin was started at 10 mg/m2 per day, and increased to 15 mg/m2 per day and 20 mg/m2 per day, if treatment was feasible in successive cohorts of at least six patients. The radiation therapy consisted of 62-66 Gray on the tumor and the ipsilateral mediastinal nodes, 50 Gray on the mediastinum and 40-45 Gray on the supraclavicular lymph nodes. Twenty-nine patients took part in this study. Thrombocytopenia was the principal dose-limiting toxicity, with 15 mg/m2 per day of bolus or continuous infusion. Other toxicities included a fall in haemoglobin level, a fall in white-blood cell count, nausea and vomiting. The median survival time was 12 months, but the response rate cannot be determined among patients selected on the basis of response to chemotherapy. The recommended Phase II dose for patients previously treated with cisplatin containing chemotherapy, is 10 mg/m2 per day of either a bolus or continuous infusion.

We report two cases of perindopril-associated pneumonitis with typical drug-induced clinical features. In the first case, biopsies showed granulomatous sarcoid-like lesions; in the second, bronchial wall eosinophil infiltratf2p4was reported with increased blood eosinophil count. In these two cases, improvement was obtained by withdrawal of the drug and was completed with steroids. All other causes were ruled out. Angiotensin-converting enzyme inhibitor (ACEI)-induced pneumonitis is still rare but has to be recognized as a real side-effect.

The reappearance of tuberculosis in France, in Europe and throughout the world has rekindled interest not only in curative treatment of the disease but also in its prevention. Since its appearance in 1921, the BCG vaccine has been the subject of debate; however, recent studies have fully demonstrated its interest, particularly in countries where tuberculosis is most endemic. The technical aspects of the treatment have changed little and are essentially based on intrademic administration, but the impact of BCG, especially for individual protection, are discussed. Its role in protection of the general population and in prevention of tuberculosis requires careful analysis. Study of iatrogenic effects of the vaccine shows that its side effects are minor when recommendations for use are followed. With the development of molecular biology techniques and mycobacteria genetics, the future use of the BCG vaccine seems promising.

OBJECTIVE--To assess the prevalence of distal airway obstruction and its risk factors in agricultural areas. METHODS--A cross sectional study of respiratory symptoms and lung function was performed among French farmers and their spouses (1122 subjects) who came for preventive medicine examinations. They answered a respiratory questionnaire and performed pulmonary function tests on a portable spirometer. Diagnoses of chronic bronchitis were made on the basis of reported chronic respiratory symptoms. Airway obstruction was determined from predicted values. Odds ratio (OR) and linear regression coefficients were calculated after stratification by smoking and history of cardiac and other respiratory diseases. RESULTS--Of respiratory symptoms prevalence of chronic cough was 8.47%, and chronic bronchitis 7.66%. Prevalence of distal airway obstruction was 11.4%, and overall airflow obstruction 3.2%. Smokers were 20.2% men, and 5.7% women. Linear regressions showed high association between pack-years in smokers or exsmokers and forced expiratory volume in one second/forced vital capacity (FEV1/VC) and forced expiratory flow between 25% and 75% of vital capacity (FEF25-75). In non-smokers without any history of cardiac or respiratory diseases, age and the size of farms had the highest correlations with these variables. OR for distal airway obstruction was 2.1 in subjects > 50 years old v the younger ones and 3.02 in the smaller farms v the larger ones. CONCLUSION--After stratification by smoking and history of cardiac and respiratory diseases, distal airway obstruction is present in agricultural areas. The age, and the size of farm are the highest respiratory risk factors in non-smokers.

Respiratory diseases are known to have consequences on health status. The objective of this study was to assess the quality of life of subjects with obstructive respiratory disorders coming for preventive medicine examinations. We conducted a study on a sample of adults living in agricultural areas (n = 1,235). We used two questionnaires: a respiratory questionnaire and the Nottingham Health Profile (NHP), which is a questionnaire designed to capture self-reported morbidity. It has been recently validated in french. Each subject performed a pulmonary function test on a portable spirometer to separate lung function obstructive abnormalities. Statistical analysis was realized by non parametric test. The number of positive responses (which shows bad health status) and the scores of the six dimensions are higher in females than males. According to sex and smoking habits, cough and chronic bronchitis are responsible for bad scores of health profile (for the total number of positive responses and the scores of each dimension). In case of airway obstruction, there is no major consequences on health profile. Subjective health measurements are interesting tools in subjects with non-chronic diseases. They can be associated with medical questionnaires because they give complementary inquiries.

Between February 1992 and May 1993, 22 patients older than 75 years, with non small cell lung cancer, were treated with carboplatin and oral etoposide. There were 18 men and four women with a median age of 79 years. Fourteen patients had an epidermoid carcinoma: four had an adenocarcinoma and four had an undifferentiated carcinoma. Carboplatin was administered intravenously on day 1 at a dose of 300 mg/m2; oral etoposide was administered at a dose of 600 mg/m2 (two capsules daily) for 9, 10, 11, or 12 days according to body surface. Courses were repeated every 28 days for a total of three courses.15 patients (68%) had received previous chemotherapy. Myelosuppression was the main problem with one grade IV and five grade III hematologic toxicities. We observed one mild neurologic toxicity.19 patients were evaluable for response. We observed one complete response (5%), five disease stabilizations (26%) and 13 disease progressions. Median survival was 5 months. These results led to discontinue this study.

Utilization of Diagnosis Related Groups (DRGs') for hospital payments in France.To search the variations and the explicative factors of length of stay in a pneumologic unit, to analyse the relevance of the indicators by using the DRG's and the supplementary variables in a medical and economical perspective.Pneumologic unit of Limoges' teaching hospital.From 1-4-93 to 31-5-94, a prospective study analysed 1081 stays (one-day-longer) by the medical unit summary and by some variables describing the stay (planned admission, appropriateness), the patient (physical mobility at entrance, severity of disease), the procedures (physiotherapy, social needs). Statistical tests associated univariate analysis, linear and logistic regressions, hierarchic segmentation.DRG's explain 23% of logarithm length of stay. The mathematical model has separated five variables, which are associated with an increase of length of stay (age, number of procedures, physical mobility at entrance, social complexity, intensity of physiotherapy), one associated with a decrease of length of stay (planned admission).DRG's, alone, do not describe the dispersion of the length of stay, which is usually used to assess the consumption of resources during an hospitalization. The record of supplementary variables needs further studies, to improve the patients' classification.