Whole-exome sequencing in patients with maturation arrest: a potential additional diagnostic tool for prevention of recurrent negative testicular sperm extraction outcomes.

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.

Anti-Müllerian hormone: A function beyond the Müllerian structures.

The anti-Müllerian hormone (AMH) is a heterodimeric glycoprotein belonging to the TGFb superfamily implicated in human embryonic development. This hormone was first described as allowing regression of the epithelial embryonic Müllerian structures in males, which would otherwise differentiate into the uterus and fallopian tubes. It activates a signaling pathway mediated by two transmembrane receptors. Binding of AMH to its receptor induces morphological changes leading to the degeneration of Müllerian ducts. Recently, new data has shown the role played by this hormone on structures other than the genital tract. If testicular AMH expression decreases in humans over the course of a lifetime, synthesis may persist in other tissues in adulthood. The mechanisms underlying its production have been unveiled. The aim of this review is to describe the different pathways in which AMH has been identified and plays a pivotal role.

Granulosa cells provide elimination of apoptotic oocytes through unconventional autophagy-assisted phagocytosis.

STUDY QUESTION: Do human granulosa cells (GCs) ingest and destroy apoptotic oocytes? SUMMARY ANSWER: Somatic GCs ingest and destroy apoptotic oocytes and other apoptotic substrates through unconventional autophagy-assisted phagocytosis. WHAT IS KNOWN ALREADY: Most (99%) ovarian germ cells undergo apoptosis through follicular atresia. The mode of cleaning of atretic follicles from the ovary is unclear. Ovarian GCs share striking similarities with testicular Sertoli cells with respect to their origin and function. Somatic Sertoli cells are responsible for the elimination of apoptotic spermatogenic cells through unconventional autophagy-assisted phagocytosis. STUDY DESIGN, SIZE, DURATION: Human GCs were tested for the ability to ingest and destroy the apoptotic oocytes and other apoptotic substrates. A systemic study of the main phagocytosis steps has been performed at different time points after loading of apoptotic substrates into the GC. PARTICIPANTS/MATERIALS, SETTING, METHODS: Primary cultures of GC retrieved following controlled ovarian stimulation of five women for IVF/ICSI and a human granulosa KGN cell line were incubated with different apoptotic substrates: oocytes which underwent spontaneous apoptosis during the cultivation of immature germ cells for IVF/ICSI; apoptotic KGN cells; and apoptotic membranes from rat retinas. Cultured GC were analyzed for the presence of specific molecular markers characteristic of different steps of phagocytic and autophagy machineries by immunocytochemistry, confocal microscopy, transmission electron microscopy and western blotting, before and after loading with apoptotic substrates. MAIN RESULTS AND THE ROLE OF CHANCE: Incubation of human GC with apoptotic substrates resulted in their translocation in cell cytoplasm, concomitant with activation of the phagocytosis receptor c-mer proto-oncogene tyrosine kinase MERTK (P < 0.001), clumping of motor molecule myosin II, recruitment of autophagy proteins: autophagy-related protein 5 (ATG5), autophagy-related protein 6 (Beclin1) and the rise of a membrane form of microtubule-associated protein 1 light chain 3 (LC3-II) protein. Ingestion of apoptotic substrates was accompanied by increased expression of the lysosomal protease Cathepsin D (P < 0.001), and a rise of lysosomes in the GCs, as assessed by different techniques. The level of autophagy adaptor, sequestosome 1/p62 (p62) protein remained unchanged. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The number of patients described here is limited. Also the dependence of phagocytosis on reproductive hormone status of patients should be analyzed. WIDER IMPLICATIONS OF THE FINDINGS: Removal of apoptotic oocytes by surrounding GC seems likely to be a physiological mechanism involved in follicular atresia. Proper functioning of this mechanism may be a new strategy for the treatment of ovarian dysfunctions associated with an imbalance in content of germ cells in the ovaries, such as premature ovarian failure and polycystic ovary syndrome. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Rennes Metropole (AIS 2015) and Agence de BioMédecine. This work was supported by funding from Université de Rennes1, Institut National de la Santé et de la Recherche Médicale (INSERM) and CHU de Rennes. A.B. is funded in part by the program Actions Concertées Interpasteuriennes (ACIP) and a research grant from the European Society of Pediatric Endocrinology. This work is supported by the Agence Nationale de la Recherche Grants ANR-17-CE14-0038 and ANR-10-LABX-73. The authors declare no competing interests.

Diagnostic yield of chromosomal microarray analysis in fetuses with isolated increased nuchal translucency: a French multicenter study.

OBJECTIVE: To determine the frequency and nature of copy number variants (CNVs) identified by chromosomal microarray analysis (CMA) in a large cohort of fetuses with isolated increased nuchal translucency thickness (NT) ≥ 3.5 mm. METHODS: This was a retrospective, multicenter study, including 11 French hospitals, of data from the period between April 2012 and December 2015. In total, 720 fetuses were analyzed by rapid aneuploidy test and the fetuses identified as euploid underwent CMA. CNVs detected were evaluated for clinical significance and classified into five groups: pathogenic CNVs; benign CNVs; CNVs predisposing to neurodevelopmental disorders; variants of uncertain significance (VOUS); and CNVs not related to the phenotype (i.e. incidental findings). RESULTS: In 121 (16.8%) fetuses, an aneuploidy involving chromosome 13, 18 or 21 was detected by rapid aneuploidy test and the remaining 599 fetuses were euploid. Among these, 53 (8.8%) had a CNV detected by CMA: 16/599 (2.7%) were considered to be pathogenic, including 11/599 (1.8%) that were cryptic (not visible by karyotyping); 7/599 (1.2%) were CNVs predisposing to neurodevelopmental disorders; and 8/599 (1.3%) were VOUS. Additionally, there was one (0.2%) CNV that was unrelated to the reason for referral diagnosis (i.e. an incidental finding) and the remaining 21 were benign CNVs, without clinical consequence. Interestingly, we identified five genomic imbalances of the 1q21.1 or 15q11.2 regions known to be associated with congenital heart defects. CONCLUSION: Our study demonstrates the benefit of CMA in the etiological diagnosis of fetuses with isolated increased NT. It is worth noting that most (69%) of the detected pathogenic CNVs were cryptic. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Pregnancy outcomes of prenatally diagnosed Turner syndrome: a French multicenter retrospective study including a series of 975 cases.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Cytogenetics profiles of renal carcinoma]. / Cytogénétique des carcinomes rénaux.

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.

Mayer-Rokitansky-Küster-Hauser syndrome patients' interest, expectations and demands concerning uterus transplantation.

OBJECTIVE: To better understand patients' conditions and expectations before starting a uterus transplantation (UTx) program for women suffering from Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome). METHOD: A web-based survey was conducted among MRKH patients via the French national association network from March to August 2020. The questionnaire comprised twenty-eight questions about their desire for parenthood, their condition's characteristics and previous reconstructive procedures, opinions and knowledge about UTx. RESULTS: Among the 148 participants, 88 % reported a desire for parenthood, and 61 % opted for UTx as their first choice to reach this aim. The possibility of bearing a child and having the same genetic heritage were the main motivations. Once informed about the usual course of an UTx protocol, only 13 % of the participants changed their mind and 3 out of 4 of them opted for UT. CONCLUSION: Uterus transplantation seems to be the first option to reach motherhood in patients suffering from MRKH syndrome. The development of UTx programs could meet the demands of this already well-informed population.

Role of chromosomal imbalances in the pathogenesis of DSD: A retrospective analysis of 115 prenatal samples.

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.

MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations.

BACKGROUND: Over the last few years, array-comparative genomic hybridisation (CGH) has considerably improved our ability to detect cryptic unbalanced rearrangements in patients with syndromic mental retardation. METHOD: Molecular karyotyping of six patients with syndromic mental retardation was carried out using whole-genome oligonucleotide array-CGH. RESULTS: 5q14.3 microdeletions ranging from 216 kb to 8.8 Mb were detected in five unrelated patients with the following phenotypic similarities: severe mental retardation with absent speech, hypotonia and stereotypic movements. Facial dysmorphic features, epilepsy and/or cerebral malformations were also present in most of these patients. The minimal common deleted region of these 5q14 microdeletions encompassed only MEF2C, the gene for a protein known to act in brain as a neurogenesis effector, which regulates excitatory synapse number. In a patient with a similar phenotype, an MEF2C nonsense mutation was subsequently identified. CONCLUSION: Taken together, these results strongly suggest that haploinsufficiency of MEF2C is responsible for severe mental retardation with stereotypic movements, seizures and/or cerebral malformations.

[The Sertoli cell]. / La cellule de Sertoli.

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.

Delineation of 15q13.3 microdeletions.

The increasing use of array-comparative genomic hybridization (array-CGH) to identify copy number variations (CNVs) in patients with developmental delay (DD), mental retardation and/or dysmorphic features has allowed the recent recognition of numerous genomic imbalances, including the 15q13.3 microdeletion. Patients with this microdeletion generally present with relatively consistent breakpoints at BP4 and BP5, which include the CHRNA7 gene. About 100 index cases have been reported since the first publication in 2008. This large number of patients ascertained through highly variable samples has been necessary to describe the full phenotypic spectrum of this microdeletion, ranging from mental retardation with dysmorphic features, epilepsy, neuropsychiatric disturbances with or without cognitive impairment to complete absence of anomalies. Here, we describe a collaborative study reporting a new cohort of 12 index patients and 13 relatives carrying a heterozygous BP4-BP5 microdeletion out of a series of 4625 patients screened by array-CGH for DD. We confirm the clinical expressivity of the disease as well as the incomplete penetrance in seven families. We showed through a review of the literature that males are more likely to be symptomatic. Sequence analysis of CHRNA7 yielded no data to support the unmasking of recessive variants as a cause of phenotypic variability. We also report the first patient carrying a 15q13.3 homozygous microdeletion inherited from both parents. He had severe epileptic encephalopathy with retinopathy, autistic features and choreoathetosis. Besides the classical approximately 1.5 Mb BP4-BP5 microdeletion, we also describe three index patients and two relatives with a smaller 500 kb microdeletion, including the CHRNA7 gene.

2q23.1 microdeletion identified by array comparative genomic hybridisation: an emerging phenotype with Angelman-like features?

BACKGROUND: Genome-wide screening of patients with mental retardation using array comparative genomic hybridisation (CGH) has identified several novel imbalances. With this genotype-first approach, the 2q22.3q23.3 deletion was recently described as a novel microdeletion syndrome. The authors report two unrelated patients with a de novo interstitial deletion mapping in this genomic region and presenting similar "pseudo-Angelman" phenotypes, including severe psychomotor retardation, speech impairment, epilepsy, microcephaly, ataxia, and behavioural disabilities. METHODS: The microdeletions were identified by array CGH using oligonucleotide and bacterial artificial chromosome (BAC) arrays, and further confirmed by fluorescence in situ hybridisation (FISH) and semi-quantitative polymerase chain reaction (PCR). RESULTS: The boundaries and sizes of the deletions in the two patients were different but an overlapping region of about 250 kb was defined, which mapped to 2q23.1 and included two genes: MBD5 and EPC2. The SIP1 gene associated with the Mowat-Wilson syndrome was not included in the deleted genomic region. DISCUSSION: Haploinsufficiency of one of the deleted genes (MBD5 or EPC2) could be responsible for the common clinical features observed in the 2q23.1 microdeletion syndrome, and this hypothesis needs further investigation.

[Anonymity of gamete donation and genetic testing]. / L'anonymat du don de gamètes à l'heure des tests génétiques.

Development of genetic testing direct-to-consumer (DTC) for recreational purposes, although prohibited in France, is a real challenge to the current practice of gamete donation. Indeed, anonymity is a fundamental principle contributing to the ethics of donation. This principle is weakened due to the availability to the general public of these tests on the Internet. Several thousands of people are conceived by gamete donation worldwide, some of whom do not know how they were conceived. Gamete donors should be informed that their anonymity is no longer guaranteed, as they can be found by homologies of their DNA, or that of a parent or a child, potentially available in databases. Thus, adults conceived by gamete donation but not informed by their parents can discover their way of conception. Recipients of gamete donation should also be informed that their child's DNA will establish the biological discrepancy and they should be encouraged to disclose the conception to their child. Several countries now allow children conceived by donation to obtain donor's identity. In France, the Bioethics Law is currently being finalized and will now allow access to donor's identity for people conceived by gamete donation.

[Neo-oogenesis in the adult ovary: What do we know?] / « Néo-ovogenèse dans l'ovaire adulte : mythe ou réalité ? ¼.

For more than a decade, the existence of ovarian stem cells that can contribute to neo-oogenesis in the adult ovary is reported by some teams, challenging the dogma according to which mammalian females are born with a fixed and non-renewed germinal cell pool. The presence of germinal stem cells with mitotic activity suggests the possibility of potential postnatal oogenesis. These cells have both germ-line and stem cell markers in culture. They have been isolated using different strategies and their ability to differentiate into oocytes has been demonstrated since after reintroduction in an ovarian somatic environment, these cells generate follicles capable of producing healthy offspring in rodents. However, many scientists remain skeptical and question the reliability of the methods used. Despite that there is no consensus on the origin of these ovarian stem cells, private companies are now proposing to use their stem cell potential to treat human infertility.

Two years' follow-up of newborn infants after extracorporeal membrane oxygenation (ECMO).

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) (n=23), neonatal sepsis (NS) (n=14), meconium aspiration syndrome (MAS) (n=12), and others (n=8). Mean gestational age and birth weight were 38+/-2 weeks and 3200+/-500 g, respectively. Oxygenation index was 61+/-8. Both venovenous (n=28) or venoarterial ECMO (n=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 (n=30), cerebral palsy (n=5), and neurologic developmental delay (n=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 (n=10), <50% stenosis (n=9), and >50% stenosis (n=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.

Effects of inhaled nitric oxide on gas exchange and acute lung injury in premature lambs with moderate hyaline membrane disease.

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, term=147 days) were randomly assigned to treatment with 20 ppm inhaled NO (n=7) from the onset of ventilation or control (n=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 PaCO(2) between 40 and 50 mmHg and post-ductal SpO(2) 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.

[Placing an endoprosthesis to maintain arterial canal permeability in lamb neonates]. / Mise en place d'une endoprothèse pour maintenir le canal artériel perméable chez l'agneau nouveau-né.

Placing an endoprosthesis in the arterial canal in order to maintain permeability is a possible alternative to performing a modified Blalock-Taussig type surgical systemico-pulmonary anastomosis. This was studied in an animal model. Twelve newborn lambs, weighing from 1.8 to 3.5 kg, were catheterised in the neonatal period in order to place a stent. Three had a partial ligature of the pulmonary artery in utero. During the initial angiography, the canal was occluded in ten of them. Different types of coronary endoprosthesis were used: Multi link tetra TM and RX Herculink TM (Guidant Europe SA), Niroyal (Boston Scientific International), Bx Velocity (Cordis, Johnson and Johnson), Jostent (Jomed). The length of the endoprostheses varied from 12 to 18 mm and the diameter from 3.5 to 6 mm. Implantation was successful 10 out of 12 times: in one case, implantation was complicated by a fatal haemopericardium, and in another by pulmonary artery embolism. Nine animals out of 10 were followed up for 1 to 2 months. At autopsy verification, the canal was permeable in 7 cases with the development of a neointima and zones of moderate stenosis with intimal hyperplasia. In 2 animals the canal was occluded at the aortic level in a zone not covered by the endoprosthesis. Three animals died after implantation: the 2 implantation failures. A third animal with a well inserted prosthesis and a permeable canal died on day 1 from an unknown cause. Placing a stent in the arterial canal is a possible alternative to performing an aorto-pulmonary shunt. Coronary stents seem well adapted and this study does not allow any conclusions to be made at this time on the best type of stent. Further studies will be necessary in order to validate this concept before its use in congenital cardiopathies.

[Important of magnetic resonance angiography with gadolinium injection in pulmonary vein diseases]. / Intérêt de l'angiographie par résonance magnétique avec injection de gadolinium dans le bilan des pathologies des veines pulmonaires.

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.

[Acinar cell carcinoma of the pancreas revealed by Weber-Christian syndrome]. / Carcinome à cellules acineuses du pancréas révélé par un syndrome de Weber-Christian.

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.