Search

OBJECTIVE To characterize the phenotypic expression of children with conductance regulator-related metabolic syndrome (CRMS)/cystic fibrosis screen positive inconclusive diagnosis (CFSPID) designation after positive newborn screening, reassign labeling if applicable and better define these children's prognosis. METHODS A multicenter cohort with CRMS/CFSPID designation was matched with cystic fibrosis (CF)-diagnosed cohort. Cohorts were prospectively compared on baseline characteristics, cumulative data and when they reached 6 to 7 years at endpoint assessment. RESULTS Compared to infants with CF (n = 63), the CRMS/CFSPID cohort (n = 63) had initially lower immunoreactive trypsinogen (IRT) and sweat chloride (SC) values, delayed visits, less symptoms, and better nutritional status; during follow-up, they had fewer hospitalizations, Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus identification, CF comorbidities, and treatment burden. At endpoint assessment, they presented a milder pulmonary phenotype on Brody computed tomography scores (0.0[0.0; 2.0] vs 13[2.0; 31.0]; P

Background: To evaluate safety and efficacy of inhaled mannitol treatment in subgroups of a large global CF population. Methods: Data were pooled from two multicentre, double-blind, randomised, controlled, parallel group phase III studies in which 600 patients inhaled either mannitol (400 mg) or control (mannitol 50 mg) twice a day for 26 weeks. Results: Both the mean absolute change in FEV1 (mL) and relative change in FEV1 by % predicted from baseline for mannitol (400 mg) versus control were statistically significant (73.42 mL, 3.56%, both p

Resume La pneumopathie necrosante a Staphylococcus aureus secreteur de toxine leucocidine de Panton-Valentine (SA-LPV+) represente moins de 1 % des pneumopathies communautaires de l’enfant et de l’adulte jeune. Les cas neonatals sont exceptionnels. Nous rapportons les observations de deux enfants nouveau-nes, des jumelles non allaitees, qui ont successivement presente une pneumopathie necrosante due a la meme souche de SA-LPV+ malgre les mesures de decolonisation nasale instaurees. Ces deux cas mettent en lumiere la possibilite d’infections pulmonaires severes a SA-LPV+ chez de jeunes nourrissons, et leur mode de transmission intrafamiliale stricte pour lesquelles les mesures d’eradication se sont averees inefficaces.

Introduction The French cystic fibrosis (CF) practice recommendations were published at the end of 2002. They advise each patient to be checked up at least once every 3 months in a reference centre for cystic fibrosis. Objective To describe the activity of the four reference centres in the Rhone-Alpes area and the patients' follow-up. Methods All patients with cystic fibrosis consulting one of the four CF centres between 1996 and 2005 were retrospectively included. All outpatient visits were recorded and classified according to (i) patient and year; and (ii) month and year. The two series were assessed graphically to determine a transition threshold, that is, the 2 consecutive years between which practices differed the most. Results A total of 616 patients were included, representing 17 594 outpatient visits. The average number of visits per patient increased from 3.7 in 1996 to 5.0 in 2005, the graphical representation showed a sharp change between 2000 and 2001. Among patients with less than 4 visits in 2000, 88 of them visited a centre 4 times or more in 2001 (44%). The annual number of outpatient visits went from 1035 to 2420. The monthly average number of outpatient visits was 86 in 1996 and 202 in 2005. The graphical representation of activity also showed a sharp change from 2001. Conclusion We showed that the implementation of guidelines occurred the year before its official publication. We also showed that the growth of this implementation was sharp rather than gradual.

Resume La maladie de Crohn (MC) affecte preferentiellement le tube digestif mais peut aussi atteindre d’autres organes : œil, foie et voies biliaires, peau, systeme osteoarticulaire. L’atteinte pulmonaire est classique mais rare. Elle peut etre primitive avec presence de granulomes, ou secondaire aux traitements. Nous presentons le cas d’une adolescente dont l’entree dans la MC a ete dominee par des symptomes respiratoires lies a une atteinte pulmonaire granulomateuse, qui ont fait d’abord suspecter une infection tuberculeuse, une sarcoidose ou une pneumopathie d’hypersensibilite.

The commercial production of Brazilian mangos is highly concentrated on cultivar 'Tommy Atkins', which has low fruit quality. Brazilian cultivars, such as IAC 110 and Roxa have been evaluated to substitute 'Tommy Atkins', although 'Keitt', 'Palmer', 'Joa', 'Bourbon' and other cultivars are also being evaluated. Some of these cultivars have been cultivated in different regions with high phenotypic variations. The objective of this work was to evaluate the genetic similarities of 11 mango genetic materials cultivated in different Brazilian regions using RAPD markers. The genomic DNA of each cultivar was extracted and amplified using 18 decamer primers to obtain RAPD markers. These markers were transformed into a binary matrix data to estimate genetic similarities among varieties and to perform cluster analysis. Of the 186 molecular markers obtained, 29.0% were monomorphic. The genetic similarities among the 11 cultivars ranged from 0.728 to 0.985. There is no genetic variation between 'Tommy Atkins' cultivated in Sao Paulo and Savanna region. The same result was observed for Keitt and Palmer cultivars. The 'Bourbon' cultivated in Sao Paulo was genetically different from 'Bourbon' cultivated in Savanna (Cerrado) region. 'Joa' was less genetically related to any other cultivar analyzed. Brazilian cultivar IAC 110 and Roxa showed the shortest genetic distances to 'Tommy Atkins'.

Embrapa Cerrados has been working on mango breeding program through intervarietal hybridization using cultivars from India, South Africa, Nigeria, Mexico, USA and Brazil since 1983. The objective of this work was to evaluate the genetic variability of 28 mango cultivars of the parental group used in the Embrapa Cerrados breeding program. The genomic DNA of each cultivar was extracted and amplified using 21 decamer primers to obtain RAPD molecular markers. These markers were transformed into a binary matrix data to estimate genetic distances among cultivars and to perform cluster analysis. From the 350 molecular markers obtained, 16.3% were monomorphic. The genetic distances among the 28 cultivars ranged from 0.098 and 0.331. The lowest genetic distances were detected between the cultivars 'Edward' and 'Glenn' (0.098), 'Tommy Atkins' and 'Keitt' (0.101), as well as 'Apple' and 'Malindi' (0.112). There is high genetic variability among mango cultivars from different countries, including the Brazilian ones. There was a grouping tendency of the important cultivars from USA. These results emphasize the importance of the cultivars used in the Embrapa Cerrados breeding program and provide useful information for future mango breeding activities.

Resume La neoangiogenese, la formation de nouveaux capillaires a partir de vaisseaux existants, joue un role central dans un grand nombre de processus physiologiques et pathologiques. Sa regulation met en jeux une pleiade de molecules exercant des activites proangiogenes ou antiangiogenes. Le monoxyde d’azote est un des principaux acteurs du declenchement de ce processus et sa production depend d’enzymes intracellulaires, les nitric oxide synthase , dont la regulation depend d’une proteine kinase B, AKT. Au cours du vieillissement, le processus de neoangiogenese est altere et ce disfonctionnement entraine un retard du processus de cicatrisation, favorise le developpement de pathologies neurodegeneratives et renales, et est particulierement prejudiciable a la revascularisation de la region du myocarde atteinte par l’ischemie ou aux developpements de vaisseaux collateraux dans les pathologies cardiovasculaires. Le systeme cardiovasculaire et en particulier le cœur subit un certain nombre de modifications structurales, moleculaires, cellulaires et fonctionnelles avec l’âge. Ces changements diminuent la capacite du cœur âge a resister a un certain nombre de stress et renforcent non seulement la sensibilite des sujets âges a l’ischemie cardiaque mais aussi sa frequence. Au cours du vieillissement le contenu en elastine diminue au detriment des fibres de collagene et des microfibrilles constituees majoritairement de fibrilline 1 dont l’expression augmente dans les fibroses cardiaques suite a une ischemie myocardique. L’elastine et les elastokines, de par leurs proprietes proangiogeniques, cardioprotectrices et regeneratrices du tissu ischemie et en contribuant a la revascularisation et au remodelage du myocarde atteint d’ischemie, pourrait constituer une alternative aux strategies therapeutiques actuelles.

International audience; Patients with cystic fibrosis (CF) experience repeated infectious respiratory exacerbations leading to a continuous decline in lung function. The exacerbations are treated in hospital or at home. Our aim was to compare the clinical outcome for patients undergoing intravenous antibiotic treatment either in hospital or at home. A retrospective 10-year study was performed in four regional CF Centers. The outcome measures were percentage changes in forced expiratory volume in 1 sec (FEV(1)), forced vital capacity (FVC) and weight for age z-score (WZS). FEV(1), FVC, and WZS changes were calculated for the entire study period and for each course. A total of 1,164 courses were analyzed. For each course, the mean improvement in FEV(1) and FVC was significantly higher when performed in hospital than when performed at home (P < 0.05). FEV(1) and FVC values were 10.2%, 9.5% respectively in the hospital group and 7.3%, 6.8% in the home group. A total of 153 patients were analyzed (51 inpatients matched to 102 patients treated at home). The two groups had no significant differences in any outcome variable at baseline. The mean variation per year in FEV(1) was greater in the hospital group versus the home group (-0.4% vs. -1.8%; P = 0.03). The mean variation per year in WZS was greater in the hospital group versus the home group (P < 0.01). Clinical outcome, as defined by spirometric parameters and body weight, was better after a course of treatment in hospital than after a home treatment. This benefit was maintained throughout of the study period.

International audience; Objective To assess whether pulmonary arteriovenous malformation (PAVM) is associated with hereditary hemorrhagic telangiectasia (HI-IT). Study design This study wits a review of 12 children (sex ratio = 1) including family history, mutation analysis, and long-term follow-up. Results Five children were under age 3 years when PAVM was diagnosed. Presentations included pulmonary, symptoms (11 8), cerebral abscess (n = 2), and transient ischemic attack (TIA) (n = 1); 1 patient was asymptomatic. Nine of the 12 children (75%) had a family history of PAVM The diagnosis of HHT was con finned in all cases. A mutation in ENG was found in 9 of the 10 children available for testing. No mutation in ACVRL1 was found. During long-term follow-up (mean, 16 years), the following complications occurred: TIA (n = 2), hemoptysis (n = 2), and cerebral abscess (n = 2). Nine children experienced recurrence of PAVM The children with no recurrence were those without a family history of PAVM. Conclusions The diagnosis of HHT should be considered in a child with an apparently isolated PAVM. Because serious complications may occur at any age, we recommend screening for PAVM and long-term follow-up in children from families with HHT, especially those with air ENG mutation.

As part of an international intercomparison project, the weak temperature gradient (WTG) and damped gravity wave (DGW) methods are used to parameterize large‐scale dynamics in a set of cloud‐resolving models (CRMs) and single column models (SCMs). The WTG or DGW method is implemented using a configuration that couples a model to a reference state defined with profiles obtained from the same model in radiative‐convective equilibrium. We investigated the sensitivity of each model to changes in SST, given a fixed reference state. We performed a systematic comparison of the WTG and DGW methods in different models, and a systematic comparison of the behavior of those models using the WTG method and the DGW method. The sensitivity to the SST depends on both the large‐scale parameterization method and the choice of the cloud model. In general, SCMs display a wider range of behaviors than CRMs. All CRMs using either the WTG or DGW method show an increase of precipitation with SST, while SCMs show sensitivities which are not always monotonic. CRMs using either the WTG or DGW method show a similar relationship between mean precipitation rate and column‐relative humidity, while SCMs exhibit a much wider range of behaviors. DGW simulations produce large‐scale velocity profiles which are smoother and less top‐heavy compared to those produced by the WTG simulations. These large‐scale parameterization methods provide a useful tool to identify the impact of parameterization differences on model behavior in the presence of two‐way feedback between convection and the large‐scale circulation., Key Points: All CRMs show a increase of precipitation with the SSTSCMs exhibit a much wider range of behaviorCRMs shows similar relationships between precipitation and column‐relative humidity

La prevalence de l'asthme et de l'asthme induit par l'exercice augmente chez les athletes de haut niveau (competiteurs nationaux ou internationaux), en particulier dans les sports d'endurance. L'hyperventilation prolongee d'un air froid ou sec ou charge de polluants et d'allergene en est une explication. L'inflammation consecutive des voies aeriennes, qui regresse apres l'arret de la competition, differe de celle de l'asthme classique. Elle pourrait representer une reponse adaptative a l'hyperventilation. Avec un traitement approprie, l'asthme et l'asthme induit par l'exercice ne sont pas un facteur limitant vis-a-vis des performances, mais les effets a court et long terme de l'entrainement sportif tres intensif necessitent une evaluation complementaire. De ce fait, une surveillance specifique est necessaire chez tous les sportifs de ce niveau, qu'ils soient asthmatiques ou non.

We retrospectively reviewed the results of serial pulmonary function tests (PFT) after allogeneic bone marrow transplantation (BMT) performed in 80 children at a single institution over a 16-year period. We looked for associations linking PFT results to graft-versus-host disease (GVHD), conditioning regimen (total body irradiation (TBI) vs busulphan), and cytomegalovirus immune status. The median follow-up after BMT was 4 years. At 2 years after BMT, significant declines were found in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), as compared to baseline. Both FEV1 and the FEV1/FVC ratio showed significantly greater reductions in the group conditioned with busulphan (n=22) than in the group conditioned with TBI (n=49) and were significantly lower in the patients with (n=16) than without (n=64) chronic GVHD. Busulphan may be associated with greater long-term lung toxicity than TBI. The relevance of this finding to selection of conditioning regimens for BMT should be examined in the light of the overall pattern of side effects. Chronic GVHD was associated with airway obstruction.

Resume Face a l’augmentation du nombre de consultations pediatriques urgentes, deux enquetes « un jour donne » ont ete menees sur le territoire de la Communaute urbaine de Lyon, avec pour objectifs l’analyse des motifs, des circonstances et de la pertinence de la non-programmation de ces demandes de soins, et la meilleure connaissance de l’itineraire des patients. Methodes. – Les consultations non programmees concernant les enfants de moins de 18 ans ont ete repertoriees le samedi 21 avril et le jeudi 13 decembre 2001 dans l’ensemble des structures susceptibles d’assurer des soins medicaux urgents. La collecte de l’information a ete realisee par questionnaire propose a la famille et aux medecins (medecins generalistes tires au sort, ou pediatres volontaires), exercant dans les secteurs de garde generalistes, a la garde du Groupement des pediatres lyonnais, et dans tous les services d’accueil d’urgence hospitaliers recevant des enfants (hopitaux publics et cliniques privees). SOS medecins n’a pas participe a l’etude, mais a communique son activite a posteriori. Six cent quatre-vingt-trois consultations le samedi et 1183 le jeudi ont ete analysees. Resultats. – En rapportant a l’ensemble des praticiens exercant le jour donne l’activite des praticiens participants sur un mode proportionnel, on pouvait estimer a 1813 le nombre total des actes le samedi et a 4576 le jeudi. La medecine liberale (cabinets et gardes organisees) en a assure 82 % le samedi (generalistes 70 %, pediatres 12 %) et 93 % le jeudi (generalistes 75 %, pediatres 18 %), les hopitaux publics 13 et 4 %, les cliniques 5 et 2 % respectivement. Pour les parents, les problemes etaient juges serieux ou graves dans 10 a 40 % des cas selon la filiere. Le motif de consultation etait le plus souvent d’ordre medical (douleur, gene physique, crainte de complications, plus rarement sentiment de gravite immediate). Les motifs non medicaux de consultation (approche du week-end, convenance personnelle, absence ou indisponibilite du medecin traitant) ont concerne un quart des consultations le jeudi et plus de la moitie le samedi. Le recours a la consultation en urgence n’etait pas justifie, selon les medecins, dans 13 % des cas. Le recours direct a une structure d’hospitalisation etait motive avant tout par l’assurance « d’avoir tout sur place ». Le samedi, l’absence du medecin traitant etait le motif le plus frequemment invoque. Le circuit du patient avant sa prise en charge etait juge globalement satisfaisant par les medecins dans 82 % des cas. Conclusion. – Les consultations non programmees correspondent a trois situations : pratique habituelle et acceptee des cabinets medicaux (consultations sans rendez-vous) ; probleme medical urgent (ou ressenti comme tel) ; resultat d’un dysfonctionnement entre l’offre de soins et son utilisation par les parents. Ce dernier point permet d’envisager deux axes d’action, l’information–education des familles et la mise en reseau des acteurs de l’urgence avec pour objectif la reduction de 15 a 20 % de l’afflux dans les hopitaux.

Ondine syndrome is the central congenital hypoventilation syndrome (CCHS) caused by the mutation of the PHOX2B gene. In late onset cases, the symptomatology often appears after an acute event (infection, general anesthesia, drug intake), increasing hypoventilation. We report a case of late onset Ondine curse in a 9-year-old girl. The diagnosis was made based on a hypercapnic coma complicating a respiratory infection caused by Mycoplasma pneumoniae and was confirmed by genetic testing. In the patient's history we found symptoms that had not been noted (e.g., enuresis, morning headache, adynamia), attesting to chronic hypoventilation. Through this observation, we review the literature on CCHS, notably late onset cases, which are rare and insidious, emphasizing the pre-existing hypoventilation symptoms in this child. This case underlines the need for all practitioners not to trivialize these symptoms so as to decrease the current delay in diagnosis for late onset CCHS and to introduce optimal care as soon as possible.

Resume Plus de 20 ans apres la decouverte du gene, en l'absence de traitement etiologique, l'amelioration observee du pronostic de la mucoviscidose apparait tout autant liee a l'organisation des soins qu'au diagnostic precoce, dans le cadre du depistage, ou a la performance croissante des traitements symptomatiques. La creation des Centres de ressources et de competence de la mucoviscidose (CRCM) a ete un prealable indispensable a la generalisation du depistage neonatal fin 2002. La prise en charge des patients et de la maladie s'est ensuite progressivement structuree au sein des 49 CRCM et de leurs reseaux de soins dans une filiere animee au niveau national par la Societe Francaise de la Mucoviscidose (SFM) creee en mars 2004, les deux centres de references (juillet 2006), en collaboration avec l'association de parents et de patients Vaincre la Mucoviscidose.

Resume Les auteurs rapportent deux observations de sensibilisation possible a la serumalbumine bovine chez des enfants âges de cinq et quatre ans. Celle-ci est associee a une intolerance au lait de vache (œdeme des paupieres et douleurs abdominales) chez le premier, a une intolerance a la viande de bœuf peu cuite chez le second (urticaire generalisee et œdeme de la face). Les profils biologiques des deux enfants sont identiques, caracterises par la presence dˈIgE specifiques vis-a-vis du lait de vache total, de la viande de bœuf et de la serumalbumine bovine. Il nˈexiste pas d’IgE specifiques dirigees contre les fractions « classiques » du lait de vache, alpha-lactalbumine, beta-lactoglobuline et caseine. Chez les deux sujets, les prick-tests sont negatifs pour le lait et ses fractions. Le prick-test est positif pour la viande de bœuf uniquement chez l’enfant intolerant a cet aliment. Il est difficile d’expliquer cette dissociation semeiologique en presence d’une vraisemblable sensibilisation commune a la serumalbumine bovine. La sensibilisation a la serumalbumine bovine est rare, surtout quand elle est isolee et, en pratique, il faut s’assurer que la recherche d’IgE vis-a-vis du lait total (Rast) comporte bien, entre autres, celle d’IgE specifiques vis-a-vis de cette proteine. Elle explique chez nos deux sujets la positivite du Rast a la fois au lait de vache total et a la viande de bœuf, mais l’exclusion d’un seul de ces deux aliments est justifiee chez chacun deux.

Resume Objectif. – Evaluer les effets physiques et psychologiques d’un entrainement sportif personnalise chez des enfants et adolescents obeses. Patients et methodes. – L’etude porte sur 36 garcons obeses âges de 12 a 16 ans, sejournant pendant au moins quatre mois au centre medical de Chanay ; 18 sont entraines selon la methode SELF. Cet entrainement est global, progressif, individualise et controle. Il se deroule sur dix semaines a raison de cinq seances par quinzaine, chaque seance durant de 30 a 45 minutes. Les parametres etudies concernent l’auxologie, l’exploration fonctionnelle respiratoire, les capacites aerobies et anaerobies, la force musculaire et les qualites psychomotrices ; les effets subjectifs de l’entrainement sont apprecies par un questionnaire qualite de vie et le hand-test. A l’inclusion, les resultats sont rapportes a une population standard. A la fin de l’entrainement, les resultats des 18 sujets entraines sont compares a ceux des 18 sujets temoins. Resultats. – Chez les enfants obeses, la puissance maximale, la capacite anaerobie, la force musculaire et les qualites psychomotrices sont diminuees par rapport a une population standard ; mais la consommation maximale d’oxygene (VO2 max) est identique en valeur absolue. Leur psychisme est marque par la maladie. Apres trois mois d’entrainement, on constate par rapport au groupe temoin une amelioration significative des aptitudes psychomotrices, une forte tendance a l’amelioration de la capacite aerobie et des effets tres benefiques sur le psychisme. Conclusion. – L’entrainement de type SELF, associe a la dietetique, apparait tres utile dans la prise en charge therapeutique de l’enfant et de l’adolescent obese. Pour etre poursuivi a domicile, il devrait etre inscrit a la nomenclature des actes de kinesitherapie.

AIM: To describe the pattern of distribution of thrombospondin (TSP1) and its receptors, alpha root of beta 3 integrin and CD36, in normal human thyroid tissue and to compare their expression in different benign and malignant thyroid conditions. METHODS: Immunohistochemistry was used to study TSP1 and its receptors in 40 surgical thyroidectomy specimens (normal parenchyma, 7; follicular adenoma, 4; multinodular goitre, 13; papillary carcinoma, 6; follicular carcinoma, 8; anaplastic carcinoma, 2). RESULTS: In the normal thyroid parenchyma, there was weak expression of TSP1 limited to the vessels with no staining of the extracellular matrix. In goitres, the expression of TSP1 was more pronounced in areas of fibrosis, with staining of alpha root of beta 3 on thyrocytes located in the vicinity. In thyroid adenomas, expression of TSP1 was slightly enhanced compared with normal tissue, located in the basement membrane of vessels. In papillary carcinomas, TSP1 was abundant in the desmoplastic stroma with a cytoplasmic distribution of alpha root of beta 3 integrin in thyrocytes. In follicular carcinomas, TSP1 was less abundant in the extracellular matrix, limited to the vessels of the stroma with a weaker expression of alpha root of beta 3 on thyrocytes than in papillary carcinomas. In anaplastic carcinomas, TSP1 was only present in the numerous capillaries of the stroma, with a marked positivity for alpha root of beta 3 in one case. No immunostaining of thyrocytes is observed with CD36. CONCLUSIONS: These results suggest the importance of the interaction between alpha root of beta 3 integrin and TSP1 during remodelling of the matrix in fibrous goitres with areas of early sclerosis comparable with wound healing. In papillary carcinomas, the overexpression of TSP1 restricted to the stroma suggests protective effects against tumour progression.

Background/Aims: Liver disease is a leading cause of morbidity in adult patients with cystic fibrosis. Diagnosis of limited liver involvement in asymptomatic patients is important since a safe and effective treatment with ursodeoxycholic acid can be used. We carried out a prospective open study to describe the intrahepatic biliary lesions using magnetic resonance cholangiography. Methods: Twenty-seven adult patients with cystic fibrosis were prospectively enrolled, whatever their hepatobiliary status. All patients underwent liver function tests, ultrasonography and magnetic resonance cholangiography. Magnetic resonance cholangiograms were acquired on a Philips 1.5 Tesla unit using a 3D TSE MR sequence. Acquisition parameters (120 slices, 1.6 mm thickness, interslice overlap 0.8 mm) were followed by MIP reconstruction in two orthogonal planes. Magnetic resonance cholangiography images were assessed for the presence of stenosis, dilatations and rigidity corresponding to current criteria of cholangitis. Among the 27 cystic fibrosis patients, 18 (Group I) fulfilled none of the clinical, biological or ultrasonographic criteria of liver disease; the remaining nine (Group II) fulfilled the criteria for liver disease. In every patient, current causes of secondary sclerosing cholangitis had been excluded. Results: All the Group II patients had abnormal magnetic resonance cholangiograms with features resembling those of primary sclerosing cholangitis in five, and simple biliary lesions in four. Nine Group I patients had abnormal magnetic resonance cholangiograms with primary sclerosing cholangitis-like lesions in five and simple biliary lesions in four. Magnetic resonance cholangiography anomalies were always dilatations, either isolated or associated with strictures and rigidity, both resembling those seen in cholangitis. They were seen in all the patients with knownliver disease and in half the patients without evidence of liver disease. Conclusion: This study confirms the high frequency of intrahepatic biliary abnormalities in CF patients, which is probably underestimated by clinical, biological and ultrasonographic evaluation. The magnetic resonance cholangiography technique could be useful to detect early intrahepatic biliary tract involvement in cystic fibrosis patients.

Chez les patients atteints de mucoviscidose, les infections virales et notamment l’infection grippale, joueraient un role important dans l’evolution respiratoire et pourraient favoriser l’infection a Pseudomonas aeruginosa . Au total, 415 patients atteints de mucoviscidose, dont 44 cas infectes par la grippe, ont ete inclus dans une etude prospective cas-temoins au cours de la grippe pandemique A/H1N1 de 2009. La fonction respiratoire et la colonisation bronchique ont ete surveillees un an apres. Au cours de la grippe, 74 % des patients ont presente une exacerbation respiratoire et 92 % ont beneficie d’une antibiotherapie. Quatre-vingt-deux pour cent ont ete traites par oseltamivir. Dans l’annee qui a suivi l’infection, la colonisation bronchique n’a pas ete modifiee, mais les cas ont recu un nombre significativement plus important d’antibiotiques (2,8 ± 2,4 chez les cas, contre 1,8 ± 2,1 chez les temoins ; p = 0,002). Nous n’avons pas mis en evidence de difference significative du VEMS a 1, 3 et 12 mois de la grippe. Au 12 e mois, l’evolution moyenne du VEMS etait de +1,2 % ( ± 13,3) pour les cas, contre –1,8 % ( ± 11) pour les temoins (NS). Deux patients ont du beneficier d’une transplantation pulmonaire au decours precoce de la grippe (l’un n’ayant pas recu d’oseltamivir, le second l’ayant recu tardivement). Notre etude n’a pas retrouve de degradation significative de l’atteinte respiratoire et de modification de la colonisation bronchique de patients atteints de mucoviscidose, apres la pandemie de grippe H1N1. Ces resultats soulignent la necessite d’administrer un traitement antiviral precoce, et de prevenir les exacerbations bacteriennes par une antibiotherapie chez ces patients presentant un episode grippal.

Resume La description recente de la polarisation Th1/Th2 des lymphocytes dans la reaction inflammatoire a permis une meilleure comprehension de la reponse inflammatoire au cours de pathologies telles que l'allergie. Decrite tout d'abord chez la souris, cette distinction de deux souspopulations lymphocytaires, Th1 et Th 2 est basee sur le profil de secretion des cytokines par ces cellules. La reponse Th1 se caracterise par les secretions d'IL-2, TNFα et IFNγ et intervient essentiellement dans les reactions de type cellulaire alors que la reponse Th2 est responsable d'une secretion d'IL-4, IL-5, IL-6, IL-10 et joue un role important dans la reponse immunitaire humorale. Si cette distinction s'avere vraie chez la souris, la situation semble plus complexe chez l'homme chez lequel on parlera plus de polarisation globale de la reponse inflammatoire que d'une differenciation achevee des lymphocytes T. Une polarisation Th2 semble caracteriser les manifestations allergiques, qu'il s'agisse de l'asthme, de la rhinite allergique ou de l'eczema. Les facteurs influencant l'evolution de la reponse inflammatoire vers un type Th2 sont multiples : la reponse immunitaire du nouveau-ne de type Th2 evoluera vers un type Th2 ou Th1 en fonction de facteurs genetiques mais egalement de facteurs environnementaux. La possibilite d'une evolution de la reaction inflammatoire d'un type Th2 vers un type Th1 permet d'envisager de nouvelles strategies therapeutiques dans le traitement des manifestations allergiques en prenant comme cible les determinants de la reponse Th2.

Resume L'agenesie bilaterale des canaux deferents est responsable d'une sterilite masculine par azoospermie excretoire et represente 1de l'ensemble des sterilites masculines. Cette forme de sterilite peut beneficier maintenant d'un programme de fecondation in vitro utilisant un prelevement de sperme epididymaire qui impose un conseil genetique en raison d'une parente genetique avec la mucoviscidose. Nous avons etudie le genotype, le taux de chlore sudoral, la fonction respiratoire, la presence d'anomalies sinusiennes, la fonction pancreatique et hepatiqu de 22 sujets presentants une agenesie bilaterale des canaux deferents (ABCD). Parmi ces 22 sujets, quatre sont heterozygotes composites, tous porteurs de la mutation R117H. Dix ont un test de la sueur positif, dont un heterozygote composite. L'association ABCD et double mutation ou test sudoral positif permet de porter le diagnostic tres probable de mucoviscidose chez 13 sujets. Six sujets sont heterozygotes, ce qui associe a l'ABCD ne permet pas de poser un diagnostic de mucoviscidose; cinq d'entre eux presentent des anomalies sinusiennes, frequentes dans la mucoviscidose, et retrouvees chez 11 des 22 sujets. Seuls trois sujets ont un test sudoral negatif et ne sont porteurs d'aucune mutation decelee. Ce travail retrouve la grande frequence des mutations du gene CFTR chez les sujets porteurs d'une agenesie bilaterale des canaux deferents, un test de la sueur frequemment positif et une frequence elevee d'anomalies sinusiennes. Cette expression phenotypique monosymptomatique suggere de nouvelles hypotheses pour expliquer les relations genotype-phenoptype dans cette pathologie.

Resume L'etude retrospective de 215 dossiers d'enfants allergiques aux venins d'hymenopteres a permis de comparer les reactions aux repiqures accidentelles dans deux groupes de patients, l'un desensibilise par venins purifies (28 sujets, 44 repiqures), l'autre non traite (25 sujets, 30 repiqures). Dans le groupe traite, 43 repiqures n'ont donne lieu qu'a des reactions locales benignes, dans tous les cas moins intenses que lors de la piqure initiale ; une repiqure a provoque une reaction identique a celle de la piqure initiale (urticaire generalisee, oedeme de Quincke et dyspnee). Dans le groupe non traite, 29 repiqures ont entraine une reaction benigne (27 fois un oedeme local ou regional, 2 fois une urticaire generalisee avec oedeme de Quincke rapidement reversible) dans tous les cas moins intenses qu'apres la piqure initiale ; une seule repiqure a provoque un tableau plus grave, mais sans collapsus (urticaire generalisee, oedeme de Quincke, signes respiratoires et digestifs). Les reactions a la repiqure different finalement peu, qu'il y ait eu desensibilisation ou non. Ceci pose une nouvelle fois la question de la justification d'un tel traitement Psychologiquement securisant, mais qui souffre, au moins a l'âge pediatrique, d'un manque de preuves incontestables d'efficacite.

More than 20 years after the gene discovery, without specific treatment, the observed improvement of the cystic fibrosis prognosis appears due to management's organization as well as early diagnosis (neonatal screening) or progress in symptomatic treatment. The CF Centers (CRCM) official recognition was a necessary step before generalization of routine neonatal screening (October, 2002). Actually French CF management relies on three levels of organization: CF centers, regional care networks and French CF Society, in close relationship with patients association (Vaincre la Mucoviscidose).

Ondine syndrome is the central congenital hypoventilation syndrome (CCHS) caused by the mutation of the PHOX2B gene. In late onset cases, the symptomatology often appears after an acute event (infection, general anesthesia, drug intake), increasing hypoventilation. We report a case of late onset Ondine curse in a 9-year-old girl. The diagnosis was made based on a hypercapnic coma complicating a respiratory infection caused by Mycoplasma pneumoniae and was confirmed by genetic testing. In the patient's history we found symptoms that had not been noted (e.g., enuresis, morning headache, adynamia), attesting to chronic hypoventilation. Through this observation, we review the literature on CCHS, notably late onset cases, which are rare and insidious, emphasizing the pre-existing hypoventilation symptoms in this child. This case underlines the need for all practitioners not to trivialize these symptoms so as to decrease the current delay in diagnosis for late onset CCHS and to introduce optimal care as soon as possible.

Resume Pour etre efficace, une prescription medicamenteuse implique l'apport d'un principe actif en concentration suffisante sur le site pathologique, sans toxicite locale ou generale, pendant le temps necessaire, dans des conditions pratiques acceptables. Ceci est particulierement vrai pour les therapeutiques inhalees, d'autant plus qu'il s'agit de nourrissons. L'efficacite depend donc de la methode elle-meme, du solvant, des caracteristiques granulometriques de l'aerosol, du mode de ventilation au cours de l'inhalation, de la nature et de la pathologie a traiter. Les caracteristiques de l'aerosol sont fonction de l'appareil (pneumatique classique ou ultrasonique), de la galenique du medicament, des conditions pratiques de realisation… La prescription doit porter sur le couple appareil-medicament. Le plus souvent les essais cliniques en terme d'aerosolisation ne sont encore qu'une estimation globale de ces differents facteurs, ce qui peut expliquer des divergences dans les resultats, qu'il s'agisse de bronchodilatateurs (beta-2-mimetiques ou atropiniques) dans le traitement des acces paroxystiques, de corticoides inhales ou de cromoglycate de sodium dans le traitement de fond.

Necrotizing Staphylococcus aureus Panton-Valentine leukocidin (SA-PLV+) accounts for less than 1% of community-acquired lung diseases in children and young adults. Neonatal cases are exceptional. We report the observations of two newborn female twins, who were not breastfed, presenting a necrotizing lung disease due to the same strain of SA-PVL+ despite nasal decolonization measures taken. These two cases are informative and bring to light (1) the possibility of severe SA-PVL+ lung infections in young infants and (2) their strictly intrafamilial mode of transmission for which eradication measures were ineffective.

We report 2 cases of multifocal cystic (type 1) pleuropulmonary blastoma, diagnosed during the first 6 months of life. This rare entity must be recognized before evolution into the prognostically unfavorable type 2 or type 3 pleuropulmonary blastoma.

Crohn disease (CD) is a chronic bowel disorder that may affect many other organs such as the eyes, hepatobiliary system, skin, and joints. Pulmonary involvement in association with CD is a classic but uncommon manifestation. It can be primitive with granulomas or secondary to treatments. We report on the case of a teenager in whom the onset of CD was dominated by respiratory symptoms. Because of this presentation, we also suspected opportunistic infections such as tuberculosis and other granulomatous pulmonary diseases such as sarcoidosis or hypersensitivity pneumonitis.

Microbiological analysis of sputum samples, from children affected by cystic fibrosis (CF) and showing signs of acute or chronic infections, is routinely performed by culture-dependent approaches involving selective media and biochemical tests. These identification schemes are time-consuming, and may lead to false negative results. The aim of this work was to evaluate the efficacy of a Ribosomal Intergenic Spacer Analysis (RISA) coupled to high performance liquid chromatography (HPLC) for the detection and monitoring of CF lung microbial colonizers including Staphylococcus aureus, Haemophilus influenzae, Pseudomonas aeruginosa, the Burkholderia cepacia complex, Stenotrophomonas maltophilia, and Achromobacter xylosoxidans. These RISA-HPLC analyses were performed over a 10-months period on infants (below 18 months) and children that were or were not yet known to be colonised by P. aeruginosa. The RISA-HPLC profiles were found specific of the patients' microbial communities. A specific P. aeruginosa RISA-HPLC peak corresponding to 550 bp PCR products was recorded, and used to investigate P. aeruginosa persistence through time and after various therapeutic treatments. The RISA-HPLC profiles showed the CF children to be colonized by few bacterial species, and sometimes revealed peaks corresponding to bacterial species that were not detected by the selective plating approaches. Significant RISA-HPLC infra-specific variations were observed for most bacterial colonizers of CF lungs except P. aeruginosa. These species could yield as much as 5 distinct RISA-HPLC peaks, with some of these profiles being strain-specific. RISA-HPLC shows a great potential for revealing colonization by novel emerging pathogens, and for evaluating the efficacy of therapeutic treatments on the global bacterial community of CF lungs.

Nitration of tyrosine residues has been observed during various acute and chronic inflammatory diseases. However, the mechanism of tyrosine nitration and the nature of the proteins that become tyrosine nitrated during inflammation remain unclear. Here we show that eosinophils but not other cell types including neutrophils contain nitrotyrosine-positive proteins in specific granules. Furthermore, we demonstrate that the human eosinophil toxins, eosinophil peroxidase (EPO), major basic protein, eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP), and the respective murine toxins, are post-translationally modified by nitration at tyrosine residues during cell maturation. High resolution affinity-mass spectrometry identified specific single nitration sites at Tyr349 in EPO and Tyr33 in both ECP and EDN. ECP and EDN crystal structures revealed and EPO structure modeling suggested that the nitrated tyrosine residues in the toxins are surface exposed. Studies in EPO-/-, gp91phox-/-, and NOS-/- mice revealed that tyrosine nitration of these toxins is mediated by EPO in the presence of hydrogen peroxide and minute amounts of NOx. Tyrosine nitration of eosinophil granule toxins occurs during maturation of eosinophils, independent of inflammation. These results provide evidence that post-translational tyrosine nitration is unique to eosinophils.

Community-acquired pneumonia is complicated by purulent pleural effusion in approximately 28% of affected children. Its incidence has increased over the last decade. Streptococcus pneumoniae is the most frequent causal microorganism, encountered in roughly 80% of cases. We report the case of an immunocompetent 13-year-old teenager wearing orthodontic braces who suffered from pleuropneumonia due to Capnocytophaga sputigena. To date, this Gram-negative bacillus, a commensal of the buccal cavity, had never been reported to be responsible for pleural or lung infection. The clinical presentation is similar to that observed with usual bacteria, while bacterial sensitivity to betalactam antibiotics is excellent.

Three children with cartilage-hair hypoplasia presented with chronic obstructive symptoms and bronchiolar wall thickening on high-resolution computed tomography scanning. In all children, surgical lung biopsy demonstrated diffuse dilated lymphoplasmacytic bronchiolitis. The bronchiolar wall was infiltrated by a lymphocyte sheath with plasma cell differentiation and dispersed secondary follicles. Clarithromycin substantially improved respiratory symptoms and pulmonary function, allowing children to return home.

Aim To evaluate an immunochromatographic membrane test for Streptococcus pneumoniae antigen (Binax NOW, Inverness medical France) applied to pleural fluid samples. Methods Binax NOW was applied to the pleural fluids of 69 children with thoracic empyema, in comparison with conventional culture and molecular techniques. Results Binax NOW was positive on all 15 pleural fluid samples that yielded S. pneumoniae in culture, on two samples that yielded S. oralis and S. salivarius in culture and on 34 culture-negative samples. Fifteen of these 34 culture-negative samples were retrospectively tested by PCR methods, and 14 were shown to contain S. pneumoniae DNA. Thus, S. pneumoniae was identified by culture in 22% of samples and by Binax NOW in 69% of samples. Conclusion Binax NOW may thus be useful for rapid diagnosis of S. pneumoniae thoracic empyema.