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L’infertilité est considérée comme un problème de santé publique majeur, et le recours aux traitements de l’infertilité est en augmentation. Chaque année, 200 000 enfants naissent dans le monde et 1 enfant sur 30 en France grâce aux techniques d’assistance médicale à la procréation (AMP). L’incidence globale des malformations congénitales (MC), y compris les formes majeures, semble augmentée chez ces enfants par rapport à celle observée chez les enfants conçus spontanément. Le risque malformatif spécifique est également augmenté avec notamment l’implication des systèmes cardiovasculaire, urogénital, nerveux et musculosquelettique. Le risque de maladies liées à l’empreinte parentale apparaît également plus élevé chez les enfants conçus par AMP. Les techniques d’AMP pourraient avoir un impact délétère. Néanmoins, d’autres facteurs sont à prendre en compte tels que l’âge parental avancé, les facteurs à l’origine de l’infertilité et le mode de vie. L’impact de l’AMP sur la santé des individus qui en sont issus est une préoccupation majeure, notamment avec l’arrivée de la nouvelle loi de bioéthique qui ouvre un accès élargi à cette procédure et qui se traduira inévitablement par une augmentation du nombre de grossesses conçues par AMP. La poursuite des recherches sur les différentes techniques d’AMP et leurs conséquences sur la santé des enfants paraît indispensable, les données issues des registres régionaux des MC pourraient apporter une aide en ce sens.

STUDY QUESTION Could whole-exome sequencing (WES) be useful in clinical practice for men with maturation arrest (MA) after a first testicular sperm extraction (TESE)? SUMMARY ANSWER WES in combination with TESE yields substantial additional information and may potentially be added as a test to predict a negative outcome of a recurrent TESE in patients with MA. WHAT IS KNOWN ALREADY At present, the only definitive contraindications for TESE in men with non-obstructive azoospermia (NOA) are a 46,XX karyotype and microdeletions in the azoospermia factor a (AZFa) and/or AZFb regions. After a first negative TESE with MA, no test currently exists to predict a negative outcome of a recurrent TESE. STUDY DESIGN, SIZE, DURATION In a cohort study, we retrospectively included 26 patients with idiopathic NOA caused by complete MA diagnosed after a first TESE. PARTICIPANTS/MATERIALS, SETTING, METHODS Twenty-six men with MA at the spermatocyte stage in all seminiferous tubules, according to a histopathological analysis performed independently by two expert histologists, and a normal karyotype (i.e. no AZF gene microdeletions on the Y chromosome) were included. Single-nucleotide polymorphism comparative genomic hybridization array and WES were carried out. The results were validated with Sanger sequencing. For all the variants thought to influence spermatogenesis, we used immunohistochemical techniques to analyse the level of the altered protein. MAIN RESULTS AND THE ROLE OF CHANCE Deleterious homozygous variants were identified in all seven consanguineous patients and in three of the 19 non-consanguineous patients. Compound heterozygous variants were identified in another 5 of the 19 non-consanguineous patients. No recurrent variants were identified. We found new variants in genes known to be involved in azoospermia or MA [including testis expressed 11 (TEX11), meiotic double-stranded break formation protein 1 (MEI1), proteasome 26s subunit, ATPase 3 interacting protein (PSMC3IP), synaptonemal complex central element protein 1 (SYCE1) and Fanconi anaemia complementation group M (FANCM) and variants in genes not previously linked to human MA (including CCCTC-binding factor like (CTCFL), Mov10 like RISC complex RNA helicase 1 (MOV10L1), chromosome 11 open reading frame 80 (C11ORF80) and exonuclease 1 (EXO1)]. LARGE SCALE DATA Data available on request LIMITATIONS, REASONS FOR CAUTION More data are required before WES screening can be used to avoid recurrent TESE, although screening should be recommended for men with a consanguineous family background. WES is still a complex technology and can generate incidental findings. WIDER IMPLICATIONS OF THE FINDINGS Our results confirmed the genetic aetiology of MA in most patients: the proportion of individuals with at least one pathologic variant was 50% in the overall study population and 100% in the consanguineous patients. With the exception of MEI1 (compound heterozygous variants of which were identified in two cases), each variant corresponded to a specific gene—confirming the high degree of genetic heterogeneity in men with MA. Our results suggest that WES screening could help to avoid recurrent, futile TESE in men with MA in general and in consanguineous individuals in particular, but these results need to be confirmed in future studies before clinical implementation. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the Fondation Maladies Rares (Paris, France), Merck (Kenilworth, NJ, USA), IRSF (Montigny le Bretonneux, France) and Agence de la Biomédecine (Saint Denis, France). There are no competing interests. TRIAL REGISTRATION NUMBER N/A.

International audience; Differences of sex development (DSDs) are a group of congenital conditions characterized by a discrepancy between chromosomal, gonadal, and genital sex development of an individual, with significant impact on medical, psychological and reproductive life. The genetic heterogeneity of DSDs complicates the diagnosis and almost half of the patients remains undiagnosed. In this context, chromosomal imbalances in syndromic DSD patients may help to identify new genes implicated in DSDs. In this study, we aimed at describing the burden of chromosomal imbalances including submicroscopic ones (copy number variants or CNVs) in a cohort of prenatal syndromic DSD patients, and review their role in DSDs. Our patients carried at least one pathogenic or likely pathogenic chromosomal imbalance/CNV or low-level mosaicism for aneuploidy. Almost half of the cases resulted from an unbalanced chromosomal rearrangement. Chromosome 9p/q, 4p/q, 3q and 11q anomalies were more frequently observed. Review of the literature confirmed the causative role of CNVs in DSDs, either in disruption of known DSD-causing genes (SOX9, NR0B1, NR5A1, AR, ATRX, …) or as a tool to suspect new genes in DSDs (HOXD cluster, ADCY2, EMX2, CAMK1D, …). Recurrent CNVs of regulatory elements without coding sequence content (i.e. duplications/deletions upstream of SOX3 or SOX9) confirm detection of CNVs as a mean to explore our non-coding genome. Thus, CNV detection remains a powerful tool to explore undiagnosed DSDs, either through routine techniques or through emerging technologies such as long-read whole genome sequencing or optical genome mapping.

Introduction L’insuffisance ovarienne primitive (IOP) atteint 1 % des femmes avant 40 ans. Un nombre croissant de genes responsables est identifie grâce au sequencage nouvelle generation (NGS). La diminution de la reserve ovarienne (DOR) concerne 10 % des femmes en parcours d’AMP, mais les etiologies sont largement inconnues. Patientes et methodes 70 patientes Caucasiennes de 16–35 ans avec DOR (AMH Resultats et discussion Quatorze patientes (20 %) portent des variants pathogenes (VP) ou probablement pathogenes (VPP) de differentes familles de genes : (1) Reparation de l’ADN : notamment une mutation tronquante de BNC1 et des VPP de ERCC6 dans deux familles non apparentees. Dans l’une d’elle, 2 sœurs ont chacune une IOP ou une DOR confirmant un mecanisme physiopathologique commun. (2) Etablissement du capital folliculaire : notamment SOHLH2 (3) Fonctions mitochondriales notamment POLG, mute dans des IOP avec atteinte neurologique, mais ici remarquablement dans une DOR isolee. Conclusion Ce travail est la premiere etude genetique complete d’une cohorte de DOR. Elle montre (i) la necessite de l’etude genetique des DOR (ii) le lien genetique entre IOP et DOR qui permettrait d’agir sur un plan preventif. Une preservation de la fertilite pourrait etre necessaire chez certaines patientes et leurs apparentees asymptomatiques. (iii) De plus la genetique pourrait apporter des elements importants sur le pronostic de fertilite des DOR.

Resume Le mesotheliome pleural malin est un cancer de mauvais pronostic et de traitement difficile. La place de la chirurgie est de plus en plus debattue dans la prise en charge des patients, la chirurgie dite « radicale » etant actuellement abandonnee, une chirurgie de reduction etant proposee dans le cadre de therapies multimodales. La chimiotherapie a base de sel de platine et d’anti-metabolite est le seul traitement pour le mesotheliome qui ait prouve son efficacite sur la survie dans des essais controles, randomises et l’association pemetrexed plus sel de platine reste le traitement de reference. Les progres en termes de comprehension de la carcinogenese et de biologie moleculaire laissent cependant esperer de nouveaux outils et strategies therapeutiques a type de traitements cibles, voire de therapies geniques ou cellulaires.

Resume Les pleuresies cancereuses sont frequentes, source d’inconfort, et d’alteration de la qualite de vie des patients. Afin de prevenir leur recidive, les options therapeutiques locales sont multiples (ponction pleurale, pleurodese chirurgicale, catheter pleural ambulatoire, bouillie talquee). Nous verrons dans cet article les avantages et inconvenients de ces differentes techniques ainsi que les recommandations actuelles afin d’aider le clinicien dans ses choix therapeutiques.

Resume La decortication est la technique qui consiste a supprimer les poches pleurales enkystees (entourees d’une gangue fibreuse) et ce quelles que soient leurs origines. Les pleuresies enkystees sont constituees de liquide exsudatif et surviennent souvent dans un contexte infectieux (pleuresie purulente, tuberculose), traumatique (sang avec inflammation et/ ou infection secondaire), ou de chylothorax (accumulation de liquide lymphatique). Les premieres techniques de decortication ont ete decrites il y a longtemps par Hippocrate. Aujourd’hui, il existe de nombreuses techniques differentes, plus ou moins invasives, allant du simple drainage avec fibrinolyse a la pleurostomie. La technique de reference de la decortication reste la thoracotomie, bien que la videothoracoscopie prenne une place de plus en plus importante et s’approprie des indications de plus en plus larges. Les indications de chacune de ces techniques sont a discuter au cas par cas entre pneumologues, chirurgiens et reanimateurs. L’indication retenue dependra de l’anciennete et de la cause de la poche pleurale, du terrain sous-jacent, et du plateau technique disponible.

Resume Les techniques chirurgicales d’exerese de la plevre sont au nombre de trois, pleurectomie decortication, pleurectomie decortication radicale et la pneumonectomie extrapleurale. Nous verrons dans cet article la place de ces differents gestes selon l’etiologie tumorale, en particulier dans le cadre du mesotheliome pleural, et selon l’indication curative ou palliative de cette chirurgie.

Resume Le pneumothorax catamenial (PC) est defini comme un pneumothorax recidivant et survenant entre la veille des regles et 72 heures apres leur debut dont la difficulte reside dans le diagnostic et la strategie therapeutique. Nous rapportons le cas de deux jeunes femmes ayant presente de nombreux episodes de pneumothorax. La premiere patiente de 28 ans avait presente 18 recidives de pneumothorax avant que le diagnostic de PC ne soit retenu. Elle beneficiait alors d’une mini-thoracotomie video-assistee qui retrouvait de multiples perforations du diaphragme qui seront suturees apres resection et biopsie. La seconde patiente presentait quatre recidives avant le diagnostic de PC, posant l’indication d’une mini-thoracotomie video-assistee permettant de mettre en evidence des breches diaphragmatiques, suturees avec pose d’un materiel prothetique resorbable, d’une pleurectomie et d’un avivement pleural. Le PC est considere comme une entite rare de pneumothorax spontane. Il est souvent associe a une endometriose thoracique. La difficulte reside dans le diagnostic (retard diagnostique frequent avec de nombreux episodes avant le debut d’une prise en charge adaptee), ainsi que dans le traitement et la necessite d’une prise en charge multidisciplinaire associant la pneumologie, la chirurgie thoracique et la gynecologie.

The Sertoli cell is essential for the formation and functioning of the testis. This is the first cell to differentiate into the initially bipotential genital ridge and is the only somatic cell present in seminiferous tubules. Maturation involves the loss of proliferative capacity, formation of intercellular tight junctions and the appearance of some specific markers. We can consider schematically two distinct roles associated with different features: a process of sexual differentiation with testicular formation and a role in spermatogenesis allowing the germ cells progression into sperm through close contact in the seminiferous tubules. These events, separated in time, are in fact intimately linked.

The fetus is able to exhibit a stress response to painful events, and stress hormones have been shown to modulate pulmonary vascular tone. At birth, the increased level of stress hormones plays a significant role in the adaptation to postnatal life. We therefore hypothesized that pain may alter pulmonary circulation in the perinatal period. The hemodynamic response to subcutaneous injection of formalin, which is used in experimental studies as nociceptive stimulus, was evaluated in chronically prepared, fetal lambs. Fetal lambs were operated on at 128 days gestation. Catheters were placed into the ascending aorta, superior vena cava, and main pulmonary artery. An ultrasonic flow transducer was placed around the left pulmonary artery. Three subcutaneous catheters were placed in the lambs' limb. The hemodynamic responses to subcutaneous injection of formalin, to formalin after fetal analgesia by sufentanil, and to sufentanil alone were recorded. Cortisol and catecholamine concentrations were also measured. Pulmonary vascular resistances (PVR) increased by 42% ( P < 0.0001) after formalin injection. Cortisol increased by 54% ( P = 0.05). During sufentanil infusion, PVR did not change significantly after formalin. Cortisol increased by 56% ( P < 0.05). PVR did not change during sufentanil infusion. Norepinephrine levels did not change during any of the protocols. Our results indicate that nociceptive stimuli may increase the pulmonary vascular tone. This response is not mediated by an increase in circulating catecholamine levels. Analgesia prevents this effect. We speculate that this pulmonary vascular response to nociceptive stimulation may explain some hypoxemic events observed in newborn infants during painful intensive care procedures.

Objective: Adaptation to extra-uterine life requires dramatic increase in pulmonary blood flow. Mechanisms that induce pulmonary vasodilatation at birth are incompletely understood but include alveolar ventilation, increase in PaO2, and production of vasoactive mediators. We hypothesized that antenatal glucocorticoids (GC) increase pulmonary vasodilatation to birth-related stimuli. Study Design: To test this hypothesis, we studied the pulmonary hemodynamic response at birth to mechanical ventilation with low (2 in chronically prepared late-gestation fetal lambs treated or not by antenatal maternal steroids. Results: Basal mean aortic and pulmonary artery pressure (PAP), left pulmonary blood flow, pulmonary vascular resistance (PVR), and blood gas were similar between control and dexamethasone-treated animals (GC group). During mechanical ventilation with low FiO2, mean PVR decreased by 40% in the control group (from 0.44 ± 0.01 to 0.25 ± 0.01 mm Hg/ml/min) and by 60% in the GC group (from 0.44 ± 0.02 to 0.19 ± 0.02 mm Hg/ml/min) (p < 0.01). When subsequently ventilated with 100% O2, there was no difference in PVR decrease between groups (0.15 ± 0.02 mm Hg/ml/min in the GC group vs. 0.14 ± 0.01 mm Hg/ml/min in the control group). Conclusion: Antenatal GC enhance pulmonary vasodilatation induced by alveolar ventilation at birth but do not alter the pulmonary vascular response to O2. We speculate that antenatal steroids exposure improve adaptation at birth through acceleration of both parenchymal and vascular lung maturation.

International audience; The objectives of this study were to report pregnancy outcomes after prenatal diagnosis of Turner syndrome (TS) and to compare and assess termination of pregnancy rates during two periods. The intervals selected were before and after 1997 when multidisciplinary centers for prenatal diagnosis (MCPDs) were established in France. A database of 975 cases of TS diagnosed between 1980 and 2012 was created from 21 French cytogenetics laboratories. For each case, the karyotype indication, maternal age, year of prenatal testing, sampling procedure, karyotype, associated ultrasound findings, and outcomes were recorded. Karyotypes were mainly performed because of abnormal sonographic findings (84%). Before 1997, there were no changes in the rate of termination (90%) of affected fetuses. After 1997, the rate fell to 80%. This decrease was mainly observed in cases of mosaicism, incidental diagnosis, and in later gestations. US abnormalities were more likely to be associated with a full 45,X karyotype. There was an evolution in the way genetic counseling was performed following prenatal diagnosis of Turner syndrome that coincided with the opening of MCPDs in France. This resulted in a decrease in the rate of termination of affected fetuses.

Resume But de l’etude : Les mecanismes de regulation de la circulation pulmonaire fœtale et les modifications hemodynamiques entourant la periode perinatale sont nombreux et restent imparfaitement compris. Le but de ce travail experimental etait de decrire un modele animal permettant une etude prolongee de la circulation pulmonaire perinatale. Materiel et methodes : Les brebis gravides ont ete operees entre 126 et 128 jours de gestation (terme = 145 jours). Chez le fœtus in utero une incision cutanee a permis d’inserer des catheters dans les vaisseaux axillaires vers l’aorte ascendante et la veine cave superieure. Puis, apres thoracotomie, des catheters ont ete places dans l’artere pulmonaire gauche, le tronc de l’artere pulmonaire, et l’oreillette gauche. Un capteur de debit et un ballonnet gonflable ont ete egalement places autour de l’artere pulmonaire gauche et du canal arteriel. L’animal ainsi prepare a fait l’objet d’etudes hemodynamiques selon divers protocoles (injection de substaces au fœtus ou a la brebis, compression du canal arteriel, test a l’oxygene, etc.). Les etudes ont ete effectuees in utero pendant dix jours (et eventuellement poursuivies lors de l’extraction fœtale) avec mesures continues de la pression arterielle pulmonaire (PAP), de la pression aortique (PAo), de la pression de l’oreillette gauche (POG), du debit arteriel pulmonaire (Q) et de la frequence cardiaque. Resultats : Sur 18 animaux operes, neuf seulement ont ete utilises pour l’experimentation. Le modele decrit a permis de realiser differentes etudes et en particulier d’etudier l’effet des catecholamines sur le tonus pulmonaire de base, et l’effet de la compression partielle du canal arteriel sur la circulation pulmonaire perinatale. Conclusion : Le fœtus de brebis opere in utero pour une etude hemodynamique chronique represente, pour une equipe entrainee, un excellent modele d’etude de la circulation pulmonaire fœtale et de ses mecanismes.

High levels of circulating catecholamines are found in the fetus, and fetal stress and birth induce a marked surge in catecholamine secretion. Little is known about the role of catecholamines on the fetal pulmonary circulation. To determine the effects of catecholamines on the pulmonary vascular tone, we tested the hemodynamic response to norepinephrine and dopamine infusion in chronically prepared late-gestation fetal lambs. We found that norepinephrine infusion (0.5 μg · kg−1· min−1) increased pulmonary artery pressure (PAP) by 10 ± 1% ( P < 0.01), left pulmonary artery blood flow by 73 ± 14% ( P < 0.01), and decreased pulmonary vascular resistance (PVR) by 33 ± 6% ( P < 0.01). The pulmonary vasodilator effect of norepinephrine was abolished after nitric oxide synthase inhibition. Dopamine infusion at 5 μg · kg−1· min−1did not significantly change PVR. Conversely, dopamine infusion at 10 μg · kg−1· min−1increased PAP ( P < 0.01) and progressively increased PVR by 30 ± 14% ( P < 0.01). These results indicate that catecholamines may modulate basal pulmonary vascular tone in the ovine fetus. We speculate that catecholamines may play a significant role in the maintenance of the fetal pulmonary circulation and in mediating changes in the transitional pulmonary circulation.

Resume La prise en charge des hernies diaphragmatiques congenitales au cours de la derniere decennie a beneficie de l'apparition de nouvelles techniques. Les mecanismes physiopathologiques responsables de l'hypoxemie dans les formes les plus graves sont egalement mieux connus. Objectif Le but de cette etude etait de verifier si la modification de la prise en charge avait eu une influence sur la mortalite des nouveau-nes porteurs d'une hernie diaphragmatique congenitale et sur leur devenir a moyen et long terme. Populations et methodes Il s'agit d'une etude retrospective portant sur les nouveau-nes porteurs d'une hernie diaphragmatique congenitale et hospitalises dans le service de medecine neonatale du CHRU de Lille entre le 1 er janvier 1985 et le 31 octobre 1996. Deux populations ont ete comparees, en fonction de la periode de prise en charge: du 1 er janvier 1985 au 31 decembre 1990 d'une part, du 1 er janvier 1991 au 31 octobre 1996 d'autre part. Les deux groupes ont ete compares en termes de mortalite ainsi qu'en termes de complications et sequelles. Resultats Cent-vingt-trois enfants ont ete admis pour hernie diaphragmatique congenitale. Neuf ont ete exclus du fait de malformations graves associees. La mortalite au terme de la periode neonatale est passee de 77 % (40 sur 52) durant la periode 1985–1990 a 44 % (27 sur 62) durant la periode 1991–1996 ( p Conclusion Les moyens actuels, l'oxygenation extracorporelle en particulier, autorisent la survie d'enfants qui, il y a quelques annees, etaient consideres comme etant au-dela de toute ressource therapeutique. Lamelioration de la survie se fait cependant au prix de sequelles plus frequentes et plus graves. L'identification de criteres fiables permettant d'evaluer le degre d'hypoplasie pulmonaire permettra de reconnaitre precocement les enfants susceptibles de developper des sequelles.

Objective: To determine whether inhaled nitric oxide (NO) may alter pulmonary vascular permeability and respiratory function in an In vivo model. Design: Prospective, randomized, controlled, experimental study. Setting: University experimental pharmacology laboratory. Subjects: Mechanically ventilated newborn piglets, 1 to 2 days old, exposed to 100% oxygen for 76 hrs. Interventions: The piglets were randomly assigned either to a treatment group receiving 20 ppm inhaled NO from the onset of ventilation (n = 5) or to a control group (n = 6) receiving no treatment Measurements and Main Results : The main variables studied were gas exchange (Pao 2 /FIO 2 ratio, lung diffusing capacity), respiratory mechanics (static compliance of the respiratory system, stat, quasi-static hysteresis area, functional residual capacity), and pulmonary vascular permeability assessed by simultaneous intravenous administration of iodine-125-labeled albumin and chromium-51-labeled red blood cells. Extravascular albumin space of the lung and dry lung weight were significantly higher in the NO group vs. the control group (albumin space, 1.08 ± 0.16 vs. 0.70 ± 0.26 [SD] mUkg body weight [p

Background Retroperitoneoscopy (RPS) is a form of direct vision endoscopy, used to explore the retroperitoneal space, and was first described by Bartel in 1969. Methods RPS was performed prospectively to diagnose infiltrating retroperitoneal lymphadenopathy or masses when needle aspiration biopsy under computed tomographic guidance (NABCT) failed to establish a definite diagnosis. Results From May 1985 to August 1995, RPS was performed in 118 patients (121 procedures). Mean hospital stay was 2.4 (range 2-5) days. The peroperative and perioperative morbidity rate was 6.6 per cent of the procedures. A precise diagnosis was obtained in 108 of the 118 patients. The sensitivity was 84 per cent for malignant lymphoma, 94 per cent for Hodgkin's lymphoma, 95 per cent for metastatic lymph nodes of carcinomas and 100 per cent for primary retroperitoneal tumours. The overall sensitivity was 91.5 per cent. Conclusion RPS is an alternative procedure to NABCT when aspiration biopsy is not technically feasible because a lesion is too small to sample or failed to establish a precise histopathological diagnosis.

Background: In view of the surgical lymphadenectomy morbidity and of the low accuracy of the preoperatory radiological investigations, minimal access surgery procedures are needed to assess lymph node involvement in pelvic cancers. Methods: Extraperitoneal pelvioscopy (EPP) is a direct vision endoscopy permitting the exploration of the retroperitoneal space of the pelvic area. Beginning 1/05/1995, 235 patients with apparently resectable tumors underwent EPP for lymph node staging of 133 bladder, 89 prostate, 12 cervix, and one endometrium cancers. Results: Lymph node involvement was discovered in 68 cases; the absence of lymph node involvement was demonstrated in 155 cases; and there were 12 false-negative results of the procedure. The feasibility was of 98.3%. The global sensitivity and accuracy were, respectively, 85% and 94%. Conclusion: This study demonstrates that EPP is a safe and accurate procedure to evaluate the lymph node status of pelvic cancers.

Renal carcinomas are histologically and prognostically heterogeneous. Genomic as well as chromosomal studies of these tumors have permitted a better comprehension of molecular mechanisms implicated in their development and progression. The most frequent histological subtypes are characterized by recurrent cytogenetic abnormalities, such as the loss of the chromosome 3 short arm involving a VHL gene copy in clear cell renal carcinomas, or trisomies 7 and 17 in papillary renal cell carcinomas. New histological subtypes like renal carcinomas associated with Xp11.2 translocations have also been individualized. Besides diagnosis, some chromosomal aberrations like the loss of a short arm of chromosome 9 in different renal carcinoma histological subtypes have a worse prognostic impact. The identification of chromosomal shuffles contributes in backing histological diagnosis and in precising the individual prognosis of patients. This review describes chromosomal abnormalities associated to renal carcinomas and their impact for an accurate classification of these tumors and the evaluation of their prognosis.

The catamenial pneumothorax (CP) is defined as recurrent pneumothorax occurring from the day before menstruations until 72 hours after their beginning, but remains a diagnostic and therapeutic problem. We herein report the cases of two young women who presented several episodes of pneumothorax. The first patient (28 years old) underwent 18 recurrent pneumothorax before the diagnosis of CP. The video-assisted mini-thoracotomy found many diaphragmatic perforations, which were sutured after resection and biopsy. The latter patient underwent four pneumothorax before diagnosis of CP. A video-assisted mini-thoracotomy associated with pleurectomy and pleural freshening was then performed. CP is a rare entity of spontaneous pneumothorax often associated with thoracic endometriosis. The difficulty remains in diagnosis (diagnostic delay before the start of appropriate care), as well as in the treatment. Overall, CP requires a multidisciplinary approach combining pulmonology, thoracic surgery and gynecology.

Sixty-five patients, aged 15 to 65 years, including 48 men (73.8%), were operated on for pulmonary (60) or endobronchial (5) hamartoma: there were 36 enucleations, 17 lobectomies (1 sleeve resection), 7 wedge resections, 4 segmentectomies, and 1 pneumonectomy. The average tumor diameter was between 2 and 4 cm; 15 were calcified. All were benign. Two were parts of an incomplete Carney's triad. Eight were associated with carcinomas, and three of these were bronchial carcinomas. Concerning these latter three tumors, a study of the incidence tables for northern France and of the standardized mortality ratio showed that the risk of bronchial cancer developing in patients with hamartoma, after a sufficient follow-up (61 patients), was multiplied by 6.66, and the chi 2 test showed a significant difference of incidence compared with that in the general population (p < 0.001). It is concluded that patients with hamartoma should be submitted to a complete evaluation and to a regular follow-up.

Backgrounds: Lung retransplantation (LRT) has become a recognized option for chronic lung graft failure. However, besides scarcity of organs or technical problems, retransplantation may be hazardous for patients on the waiting list (WL). In this study we analyzed the course of chronic lung graft failure in 5 patients and the ultimate evolution to death or LRT.

We investigated the pulmonary vascular effects of prophylactic use of sildenafil, a specific phosphodiesterase-5 inhibitor, in late-gestation fetal lambs with chronic pulmonary hypertension. Fetal lambs were operated on at 129 ± 1 days gestation (term = 147 days). Ductus arteriosus (DA) was compressed for 8 days to cause chronic pulmonary hypertension. Fetuses were treated with sildenafil (24 mg/day) or saline. Pulmonary vascular responses to increase in shear stress and in fetal PaO2were studied at, respectively, day 4 and 6. Percent wall thickness of small pulmonary arteries (%WT) and the right ventricle-to-left ventricle plus septum ratio (RVH) were measured after completion of the study. In the control group, DA compression increased PA pressure (48 ± 5 to 72 ± 8 mmHg, P < 0.01) and pulmonary vascular resistance (PVR) (0.62 ± 0.08 to 1.15 ± 0.11 mmHg·ml−1·min−1, P < 0.05). Similar increase in PAP was observed in the sildenafil group, but PVR did not change significantly (0.54 ± 0.06 to 0.64 ± 0.09 mmHg·ml−1·min−1). Acute DA compression, after brief decompression, elevated PVR 25% in controls and decreased PVR 35% in the sildenafil group. Increased fetal PaO2did not change PVR in controls but decreased PVR 60% in the sildenafil group. %WT and RVH were not different between groups. Prophylactic sildenafil treatment prevents the rise in pulmonary vascular tone and altered vasoreactivity caused by DA compression in fetal lambs. These results support the hypothesis that elevated PDE5 activity is involved in the consequences of chronic pulmonary hypertension in the perinatal lung.

Objective To characterize effects of sympathetic tone on fetal heart rate (FHR) reflex responses and FHR variability in late gestation. Design/Methods Changes in FHR and autonomic tones were studied (i) after electrical vagal stimulation and (ii) during nitroprusside-induced hypotension, in seven late gestation ovine fetus in control condition (ctrl), after dobutamine (β1-activation) and atenolol (β1-blockade). Results are expressed as mean ± SEM. Results (i) Minimal FHR after vagal stimulation was not influenced by atenolol or dobutamine but dobutamine accelerated FHR normalization. (ii) During nitroprusside induced hypotension atenolol inhibited the initial increases in FHR and FHR variability (measured by SD and LFnu) but not the bradycardia occurring below a mean arterial pressure of 38 ± 2 mmHg. Dobutamine did not abolish the depressor reflex. During hypotension the positive chronotropic effect of sympathetic tone increased from 15 ± 2 to 42 ± 7 bpm then decreased at a rate of − 7.6 ± 1.5 bpm mmHg − 1 , vagal negative chronotropic influence steadily increased at a rate of 1.9 ± 0.4 bpm mmHg − 1 . Changes in FHR variability were not correlated with vagal or sympathetic chronotropic effects. Conclusions β1-stimulation does not affect sinus-node response to vagal stimulation but improves the speed of FHR normalization. FHR response to hypotension depends on an initial increase in both sympathetic and parasympathetic chronotropic effects that is associated with a sympathetic dependent increase in FHR variability and is followed by a withdrawal of sympathetic tone.

This experimental study was performed to determine the effects of norepinephrine on: (i) the pulmonary vascular tone during the development of pulmonary hypertension (PH) in the fetus and (ii) the circulatory adaptation at birth after chronic intrauterine PH.Chronically instrumented fetal lambs were randomized into two groups: (i) a group with PH obtained by antenatal partial ligation of the ductus arteriosus (DA) (n=9) and (ii) a control group without DA ligation (n=6). Pulmonary vascular responses to norepinephrine (1.5 microg min(-1)) were measured in utero 7 days after surgery. At day 8 post-surgery, after delivery, animals were ventilated for 3 h with oxygen 100%. The group with PH was randomly assigned to receive norepinephrine or saline.Mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) were higher in the PH group (P0.01). Norepinephrine-induced decrease in PVR was more pronounced in the PH group than in the control group (63 vs 35%, respectively; P0.01). In the PH group, the decrease in PVR during mechanical ventilation was greater in the animals receiving norepinephrine than in the animal receiving saline (from 1.05 (0.12) to 0.1 (0.02) vs from 1.04 (0.1) to 0.2 (0.04) mm Hg ml(-1) min(-1), respectively; P0.01). After 3 h of ventilation, mean PVR in the PH lambs treated by norepinephrine was similar to those measured in the control lambs. Aortic pressure was higher in the group treated with norepinephrine.The data suggest that norepinephrine may improve post-natal pulmonary adaptation in the newborn with persistent PH both by increasing systemic vascular pressure and by increasing pulmonary blood flow.

Authors suggest that high incidence of persistence pulmonary hypertension among neonates delivered by elective cesarean is related to lower levels of circulating norepinephrine in neonates after cesarean section than after vaginal delivery.

The study of the pulmonary veins by echocardiography is sometimes difficult especially when the ultrasonic window is restricted. Conventional angiography is the classic reference examination but it exposes the patient to ionising radiation and requires the injection of an iodine contrast product. Another technique that can provide the essential information is magnetic resonance angiography (MRA) with injection of gadolinium. It was performed in 9 patients for suspected congenital or acquired anomalies of the pulmonary veins between June 1999 and December 2001. The patient's ages varied from 1 month to 10 years. The examinations were carried out on a 1.5 T Vision machine (Siemens, Erlangen, Germany) without "cardiac gating" or apnoea after parental consent. MRA with gadolinium injection showed 5 drainage anomalies (3 partial pulmonary venous refluxes in the superior vena cava, 2 scimitar syndromes) and 3 stenoses (one due to compression by an aneurysm of the left pulmonary artery, a second secondary to pericardial agenesis, and a third secondary to hypoplasia of an isolated vein). MRA allowed three dimensional visualisation of these anomalies. This is a rapid, non-invasive and certain imaging technique which does not expose the patient to ionising radiation. It is therefore of significance in the investigation of anomalies of the pulmonary veins complementing echocardiography, and could in future replace cardiac catheterisation.

Mechanisms that modulate fetal pulmonary circulation and transitional circulation at birth are incompletely understood. The aim of this experimental study was to describe an animal model in order to study the perinatal pulmonary circulation.Pregnant ewes were operated on between 126 and 128 days gestation (term = 145 days). A skin incision was performed to the fetal lambs in utero and catheters were placed into the ascending aorta and the superior vena cava after insertion in the axillary artery and vein. Then, catheters were inserted into the left pulmonary artery (LPA), main pulmonary artery, and left atrium via a thoracotomy. Moreover, an ultrasonic flow transducer, and an inflatable vascular occluder were placed around the LPA and around the ductus arteriosus. During 10 days, studies were performed in utero (possibly continued when fetal lambs were delivered by caesarean section). This chronically prepared animal may be used to perform hemodynamic studies according to different protocols (drugs injection to the fetus or to the ewes, ductus arteriosus compression, oxygen test). The main pulmonary artery, aortic, left atrial and amniotic pressures, heart rhythm, and flow signal were continuously recorded.Eighteen pregnant ewes were operated on and nine only could be used for experimentation. This ovine model permitted several studies, particularly about effects of catecholamines on the pulmonary circulation, and about effects of ductus arteriosus compression on the pulmonary circulation.Chronically instrumented fetal lambs are an excellent model in order to study the perinatal pulmonary circulation.

Objective: The purpose of this study was to examine whether inhaled nitric oxide (iNO) may change lung injury in moderate hyaline membrane disease (HMD). Methods: Fifteen moderately premature lambs (128 days gestation, terma 147 days) were randomly assigned to treatment with 20 ppm inhaled NO (na 7) from the onset of ventilation or control (na 8). Except for inhaled NO, treatments were intentionally similar to those applied in clinical situations. After porcine surfactant administration (Curosurf, 100 mg/kg), mechanical ventilator settings were modified during the course of the study to maintain PaCO2 between 40 and 50 mmHg and post-ductal SpO2 between 90 and 95%. The main studied parameters were gas exchanges parameters, respiratory mechanics (static compliance and functional residual capacity) and pulmonary vascular permeability and/or filtration rate indices. Results: We found that 20 ppm of inhaled NO for 5 h significantly reduce ventilatory and oxygen requirements, but only during the first hour of mechanical ventilation. No increase in extravascular lung water content (5.41 ^ 0.96 vs. 5.46 ^ 1.09 ml/g bloodless dry lung in the control group and in the NO group, respectively) and no impairment of the respiratory mechanics could be found in the NO-treated group. However, inhaled NO increased the albumin lung leak index in this model (6.09 ^ 1.51 in the NO-treated group vs. 4.08 ^ 1.93 in the control group; P , 0:05). Conclusions: Our results do not therefore support a detrimental effect of short-term exposure to low doses of NO inhalation in moderate HMD. However, it may induce an increase in lung vascular protein leakage. The pathophysiological consequences of this finding remain to be elucidated. q 2000 Elsevier Science B.V. All rights reserved.

Objective: Extracorporeal membrane oxygenation (ECMO) is a technique of extracorporeal oxygenation used in newborn infants with refractory hypoxemia after failure of maximal conventional medical management, when mortality risk is higher than 80%. We retrospectively reviewed all the neonates treated by ECMO between October 1991 and September 1997 in our newborn intensive care unit. Methods: Fifty-seven patients were treated with ECMO for severe respiratory failure: congenital diaphragmatic hernia (CDH) (na 23), neonatal sepsis (NS) (na 14), meconium aspiration syndrome (MAS) (na 12), and others (na 8). Mean gestational age and birth weight were 38 ^ 2 weeks and 3200 ^ 500 g, respectively. Oxygenation index was 61 ^ 8. Both venovenous (na 28) or venoarterial ECMO (na 29) were used. The mean time at ECMO initiation was 47 h (range 8 h‐2 months). The mean duration was 134 ^ 68 h. In each case of VA ECMO, carotid reconstruction was performed. Survival at 2 years was 40/57 (70%) (CDH 12/23 (52%), NS 11/14 (79%), MAS 12/12 (100%), others 5/8). Follow-up at 2 years was available in 36 survivors. Results: Neurodevelopmental outcome was not related to the initial diagnosis: normal neurologic development (na 30), cerebral palsy (na 5), and neurologic developmental delay (na 1). Two patients remained oxygen dependant at 2 years, and four required surgical treatment for severe gastroesophageal reflux. Respiratory and digestive sequelae were more frequent in the CDH group (P , 0:01). Patency and flow of the repaired carotid artery was assessed in 20 infants at 1 year of age using Doppler ultrasonography: normal (na 10), , 50% stenosis (na 9), and . 50% stenosis (na 1). Conclusion: ECMO increased survival of newborn infants with refractory hypoxemia. However, higher a survival rate and lower morbidity were found in non-CDH infants than in congenital diaphragmatic hernia. q 2000 Elsevier Science B.V. All rights reserved.

Lumboscopy is an endoscopic surgical technique providing direct visualization of the retroperitoneal space from the kidney hilium to the iliac bifurcation. We report our 10-year experience with this technique used to diagnose masses in the retroperitoneal space. This method is not very invasive and the morbidity is low. The sensitivity is greater than needle biopsy under CT guidance.

The frequency of lung cancers associated with synchronous head and neck malignancies can be evaluated between 1.5 to 2%. The purpose of our work was to determine if complete endoscopic head and neck examination performed under general anesthesia was superior than clinical head and neck examination for the diagnosis of these synchronous additional tumors. From july 1991 to august 1992, we realised a prospective study on 58 consecutive patients suffering from pulmonary removable lung cancers. All the patients had a clinical head and neck examination during the preoperative period. Immediately before thoracotomy a complete endoscopy of head and neck aerian and digestive tract was performed. During this last examination 18 new macroscopical lesions were discovered in 13 patients: benign lesions (n = 17), oral cavity and laryngeal dysplasia (n = 1). The one gingivolingual sulcus carcinoma, already discovered by the clinical examination, was confirmed. This study suggests that complete head and neck endoscopy is not superior than clinical examination for the diagnosis of synchronous malignancies before lung cancers removal.

Acinar cell carcinoma of the pancreas is a rare tumor of the exocrine pancreas that may be associated with a characteristic syndrome of disseminated fat necrosis with a bad prognosis. We report a case of this tumor occurring in a 63 year-old man who presented with polyarthralgia and panniculitis of the legs. The histological features and the differential diagnosis of acinar cell carcinoma are discussed.

Background: Nitric Oxide (NO) released by pulmonary vascular endothelium is a potent vasodilator related to increased cGMP content. Hydrolysis of cGMP is achieved predominantly by cGMP–specific phosphodiesterases (PDEs). Sildenafil (SILD) is a selective phosphodiesterase–5 (PDE–5) inhibitor. The purpose of the study was to assess the effects of sildenafil on pulmonary vascular circulation during the perinatal period.

Potential beneficial and/or detrimental effects of inhaled NO on oxidant-induced lung injury have not been fully investigated in newborn infants. The purpose of this investigation was to examine whether inhaled nitric oxide (NO) may alter pulmonary vascular permeability and respiratory function in mechanically ventilated newborn piglets -1 to 2 days old-, exposed to 100% O2 for 76 hours. They were randomly assigned to treatment with 20 ppm inhaled NO (n=5) from the onset of ventilation or control (n=6). Peak inspiratory pressure was set to maintain PaCO2 between 35 and 45 mmHg. The other ventilator parameters were not changed during the course of the study (FiO2=1; PEEP=5cmH2O; RR=25/min). The main studied parameters were gas exchange (PaO2/FiO2 ratio, lung diffusing capacity=DLCO), respiratory mechanics (static compliance of the respiratory system=Crs,stat measured at 5, 10, 15, and 20 ml/kg during inspiration and expiration, quasi-static hysteresis area, functional residual capacity=FRC) and pulmonary vascular permeability assessed by simultaneous intravenous administration of 125I-labeled albumin and 51Cr-labeled red blood cells. PaO2/FiO2 decreased significantly between 2 and 76 hours of 100% O2 exposure in the control and the NO groups (from 388±63 to 225±63 and from 375±84 to 200±64 mmHg respectively). The extravascular albumin space of the lung and the dry lung weight were significantly higher in the NO group versus control group (Alb space: 1.08 ± 0.16 ml / kg body weight versus 0.70 ±0.26 ml / kg body weight and dry lung weight: 3.20 ± 0.34 g / kg body weight versus 2.66 ± 0.14 g / kg body weight respectively). Moreover, hysteresis area was higher from 24 hours of NO exposure. Conversely, NO inhalation did alter neither the extravascular lung water content (12.98 ± 2.79 ml / kg body weight in the NO group versus 12.18 ± 2.26 ml / kg body weight in the control group; NS), nor the main respiratory mechanic parameters (Crs,stat, FRC) and gas exchange (DLCO, PaO2/FiO2 ratio). In conclusion, our results do not support the hypothesis that NO inhalation combined with hyperoxia may alter the main lung function parameters in neonates. However, it may induce an increase in lung vascular protein leakage. Pathophysiological consequences of this finding remain to be elucidated.

Does Inhaled Nitric Oxide (No) Modify Lung Function and Oxidative Stress Parameters in Experimental Hyaline Membrane Disease (Hmd)? 231

DOES INHALED NITRIC OXIDE MODIFY LUNG DIFFUSING CAPACITY AND MECHANICS IN EXPERIMENTAL HYALINE MEMBRANE DISEASE (HMD)? 2073

Gas exchange improvment by low dose NO inhalation without increase of vascular permeability was reported by Kinsella et al. in experimental severe HMD (Pediatr Res 1995; 38: 337A). Our hypothesis was that inhaled NO could be deleterious in less severe respiratory failure by increasing pulmonary blood flow and/or altering vascular permeability. The effects of inhaled NO on gas exchange and lung vascular permeability in moderate HMD were studied. Eighteen moderatly premature lambs (130 days gestation, term=147 days) were randomly assigned to treatment with 20 ppm inhaled NO from the onset of ventilation(HO) or control. After porcine surfactant administration (Curosurf® 100 mg/kg), ventilator was set to maintain PaCO2 values between 40 and 50 mmHg and SpO2 values between 90 and 95%. After 4 hours,125 I-labeled albumine and 51Cr-tagged red blood cells were injected. One hour later, gamma-counting was performed on lung tissue and blood. Wet and dry weights of blood and lung were measured. Pulmonary edema was assessed by measurement of extravascular lung water content (Qwl) normalized for bloodless dry lung weight. Vascular permeability was evaluated by the Lung Leak Index (LLl) measurement (Am Rev Respir Dis. 1993; 148: 1194-203). Oxygenation (OI = Mean Airway Pressure*FiO2/PaO2) and ventilatory index (VI = Mean Airway Pressure*Respiratory Rate) were calculated at 1 and 5 hours. OI was significantly lower after 1 hour of ventilation in the NO vs. control group. However, OI and ventilatory requirement were not significantly different after 5 hours of ventilation. In spite of similar extravascular lung water content in both groups, vascular protein leak was increased in NO group. In conclusion, no benefit of short term NO inhalation (5 hours) could be demontrated for gas exchange in premature lambs with moderate HMD. Moreoever increased lung vascular protein leak in the NO group suggests an alteration of vascular permeability. Benefits of long term NO inhalation should be demonstrated before its clinical use in moderate HMD.Table