Prenatal microarray comparative genomic hybridization: Experience from the two first years of activity at the Lyon university-hospital.

OBJECTIVES: This study aims to describe how microarray comparative genomic hybridization (aCGH) has shifted to become a prenatal diagnosis tool at the Lyon university-hospital. MATERIALS AND METHODS: This retrospective study included all patients who were referred in the 3 pluridisciplinary centers for prenatal diagnosis of the Lyon university-hospital and who received a prenatal aCGH between June 2013 and June 2015. aCGH was systematically performed in parallel with a karyotype, using the PréCytoNEM array design. RESULTS: A total of 260 microarrays were performed for the following indications: 249 abnormal ultrasounds (95.8%), 7 characterizations of chromosomal rearrangements (2.7%), and 4 twins with no abnormal ultrasounds (1.5%). With a resolution of 1 mega base, we found 235 normal results (90.4%), 23 abnormal results (8.8%) and 2 non-returns (0.8%). For the chromosomal rearrangements visible on the karyotype, aCGH identified all of the 12 unbalanced rearrangements and did not identify the 2 balanced rearrangements. Among the fetuses with normal karyotypes, 11 showed abnormal microarray results, corresponding to unbalanced cryptic chromosomal rearrangements (4.2%). CONCLUSION: Transferring aCGH to a prenatal diagnosis at the Lyon university-hospital has increased the detection rate of chromosomal abnormalities by 4.2% compared to the single karyotype.

[Fetal transcerebellar diameter measured in screening ultrasound: Feasibility and reproducibility]. / Mesure du diamètre transverse du cervelet en échographie de dépistage : faisabilité et fiabilité.

OBJECTIVE: The aim of the study was to evaluate feasibility and reproducibility of fetal transcerebellar diameter measurement during second and third trimester ultrasound mass screening by junior and senior physicians. MATERIALS AND METHODS: A monocentric prospective study was conducted at the tertiary care teaching hospital in Lyon, including patients undergoing their second or third trimester planned ultrasound exam. For each patient, a resident and a senior practitioner measured each fetal transcerebellar diameter, during a blinded experiment, according to the transcerebellar plane described by the International Society of Ultrasound in Obstetrics and Gynecology. Images have been scored on 4 criteria. The inter-observer variability for transcerebellar diameter and image quality was assessed using an intra-class correlation coefficient. Image quality has been analyzed according to pregnancy term and to fetal presentation. RESULTS: Sixty-six patients were included, 44 patients before and 22 patients after 30 weeks. Inter-observer variability of transcerebellar diameter measurement was 0.4%. Inter-observer variability of image quality was 13.5%. Image quality was not significantly different between seniors and residents (P=0.06). Gestational age and fetal presentation did not affect significantly image quality (P=0.42) and (P=0.64) respectively. CONCLUSION: Transcerebellar diameter measurement during mass screening is simple and reliable. Posterior fossa abnormalities can be explored through its measurement.

Evolutionary origins of the placental expression of chromosome 19 cluster galectins and their complex dysregulation in preeclampsia.

INTRODUCTION: The dysregulation of maternal-fetal immune tolerance is one of the proposed mechanisms leading to preeclampsia. Galectins are key regulator proteins of the immune response in vertebrates and maternal-fetal immune tolerance in eutherian mammals. Previously we found that three genes in a Chr19 cluster encoding for human placental galectin-13 (PP13), galectin-14 and galectin-16 emerged during primate evolution and may confer immune tolerance to the semi-allogeneic fetus. MATERIALS AND METHODS: This study involved various methodologies for gene and protein expression profiling, genomic DNA methylation analyses, functional assays on differentiating trophoblasts including gene silencing, luciferase reporter and methylation assays. These methods were applied on placental specimens, umbilical cord blood cells, primary trophoblasts and BeWo cells. Genomic DNA sequences were analyzed for transposable elements, transcription factor binding sites and evolutionary conservation. RESULTS AND DISCUSSION: The villous trophoblastic expression of Chr19 cluster galectin genes is developmentally regulated by DNA methylation and induced by key transcription factors of villous placental development during trophoblast fusion and differentiation. This latter mechanism arose via the co-option of binding sites for these transcription factors through promoter evolution and the insertion of an anthropoid-specific L1PREC2 transposable element into the 5' untranslated region of an ancestral gene followed by gene duplication events. Among placental Chr19 cluster galectin genes, the expression of LGALS13 and LGALS14 is down-regulated in preterm severe preeclampsia associated with SGA. We reveal that this phenomenon is partly originated from the dysregulated expression of key transcription factors controlling trophoblastic functions and galectin gene expression. In addition, the differential DNA methylation of these genes was also observed in preterm preeclampsia irrespective of SGA. CONCLUSIONS: These findings reveal the evolutionary origins of the placental expression of Chr19 cluster galectins. The complex dysregulation of these genes in preeclampsia may alter immune tolerance mechanisms at the maternal-fetal interface.

[First-trimester cystic hygroma: prenatal diagnosis and fetal outcome]. / Hygroma kystique découvert à l'échographie obstétricale du 1er trimestre : caractéristiques échographiques, caryotypiques et devenir de la grossesse.

OBJECTIVES: To describe the ultrasonographic (US) and fetal karyotyping data of fetuses with cystic hygroma diagnosed in the first trimester. PATIENTS & METHODS: Maternal and fetal data of 69 consecutive fetal cystic hygroma were analysed between 2002 and 2009. RESULTS: The mean size of the cystic hygroma was 6.3 mm ± 2.4 mm. US abnormalities were present in 54% of cases (37/69) (essentially hydrops fetalis in 45%), with an unfavourable prognosis (P=0.006). Chromosomal abnormalities were present in 53% of cases (36/68) (including 44% of Down syndrome). The rate of unfavourable outcome of pregnancy was 71% of cases (49/69) and was associated with the oldest mothers (P=0.011). In the chromosomally normal pregnancies, there were 59% (19/32) fetus with no apparently abnormalities. Among these 19 children, 13 have been followed up until an average age of 5 years and a half, the infant development was strictly normal. DISCUSSION AND CONCLUSION: The current results suggest to look for the poor prognosis data: nuchal thickness superior to 6 to 6,5 mm, presence of a hydrops fetalis and/or US abnormalities, fetal karyotyping and/or US evolution of cystic hygroma.

Evaluation of ready-to-use and multi-dose influenza vaccine formats in large clinic settings.

Large immunization clinics are commonly held to deliver influenza vaccine to seniors and others. Vaccine is typically dispensed from multi-dose vials but pre-filled syringes are now available, offering time savings for vaccinators. To determine if the higher purchase price of such syringes is offset by savings in time and injection supplies, we did a controlled comparison of syringe and vial formats in two large, concurrent, community-based influenza vaccination clinics. Vaccine preparation and immunization times were carefully documented along with costs for vaccine purchase, storage and injection supplies. Servicing 1,000 clients required 27 nurse hours using syringes and 36 hours using vials but the savings for personnel ($234) and supplies ($1,190) using syringes were exceeded by higher vaccine cost ($2,090 premium) and extra storage costs ($260) for bulkier packaging. Depending upon product and packaging style, programs using vials are cheaper by $709-$926 per 100 doses delivered compared to using pre-filled syringes.

[Cognitive inhibition and psychopathology: toward a less simplistic conceptualization]. / L'inhibition cognitive et la psychopathologie: vers une conceptualisation moins simpliste.

"Cognitive inhibition" is a concept that has found a firm place in the interpretation of performance by normal subjects on tasks involving adherence to a plan and suppression of incorrect responses to distractors. The presence of "negative priming" is the classical indicator of cognitive inhibition. Negative priming occurs when, in a sequence of stimuli each of which is composed of a target and a distractor, the distractor of the first stimulus becomes the target of the second stimulus: reaction time to the second stimulus is slowed because of the inhibition applied to the distractor of the first stimulus. The concept has been extended to the interpretation of pathological behavior and symptoms. Pathological subjects have been found to show deficient negative priming. Thus, negative ideation in depression as well as intrusive paranoid associations in schizophrenia have been related to a deficit in the capacity to inhibit inappropriate representations. In this paper, we briefly review some of the experimental evidence from normal subjects that has contributed to the acceptance of cognitive inhibition as a key process in the control of normal cognition, as well as more recent evidence that has led to a revision of the concept. Negative priming in normal subjects has been found to be dependent upon characteristics of the experimental situation as perceived by the subject. In particular, priming is observed when the subject anticipates difficulty in determining the response and proceeds with caution. Thus, inhibition is not an automatic "brake" applied to irrelevant material, but rather the product of strategic considerations within the experimental situation. This revision of the cognitive inhibition hypothesis leads to a re-interpretation of the apparently deficient cognitive inhibition seen in depressed or schizophrenic subjects. According to this more recent interpretation, deficient cognitive inhibition in pathological subjects can be seen as a less adaptive strategic adjustment to the task. The pathology seems to touch higher-level executive functions rather than a deficient inhibitory "brake". In depressed subjects, abnormal performance in selective attention tasks could be related to the underlying pathology in two ways: some depressed subjects show a marked lack of energy and a psychomotor slowing: these subjects do not exhibit normal negative priming, probably because of a reduction of cognitive resources. Other depressed subjects show abnormal performance as reflected by negative priming greater than normal: this result could be related to an exaggerated tendency to verify a correct response. Schizophrenic subjects show a lack of negative priming that seems most plausibly to be related to an ineffectual integration of the experimental instructions concerning both speed and accuracy in the response. This re-interpretation of the cognitive deficiency in pathological patients provides a better fit with recent experimental results from normal subjects, and with cognitive deficits measured in pathological subjects.

[Deficit in suppression of interference in visual information processing by schizophrenic subjects]. / Déficit dans la suppression de l'interférence au niveau du traitement de l'information visuelle chez des patients schizophr nes.

Although many studies have indicated information processing deficits in schizophrenic patients, the precise nature and underlying causes of these deficits remain largely uncertain. One prominent hypothesis is that these patients show insufficient attentional inhibition. This deficit to inhibition has been linked to certain cognitive disorders in schizophrenic patients, including attention deficits, as well as to some clinical symptoms, especially those involving delusional thought, hallucinations,and poor contact with reality. The hypothesis of deficient attentional inhibition, although attractive in some ways, is difficult to work with, because it is not easy to directly measure "attentional inhibition". Several studies involving normal subjects have linked attentional inhibition with performance on a task demanding the suppression of distracting information: the presumption is that efficient attentional inhibition will permit rapid responses because the distracting information will be quickly suppressed, allowing undistracted processing of the target information. The present study measures schizophrenic patients' performance on a task demanding suppression of rapidly-presented visual information. An important methodological feature of this study is that performance is measured in terms of "percent correct responses" rather than the reaction time measures typically used in tasks demanding distractor suppression, such as Stroop-like selective attention tasks. Since reaction times are not considered, the results cannot be interpreted in terms of deficient response organization and execution. Schizophrenic (18) and normal (18) subjects underwent trials in which a visual target was the second of two stimuli presented in rapid succession. Interference produced by a non-target significantly impaired perception of the target for schizophrenic patients. This effect persisted longer in the schizophrenic subjects possibly because of deficient attentional inhibition.

Effect of reminder notices on the timeliness of early childhood immunizations.

OBJECTIVE: To determine whether reminder notices would improve the timeliness of toddler-age vaccinations. DESIGN: Prospective, randomized, controlled trial. POPULATION STUDIED: Two convenience cohorts of 320 children due to receive either measles-mumps-rubella (MMR) vaccine (at 12 months of age) or diphtheria-pertussis-tetanus (DPT)-inactivated polio (IPV)- Haemophilus influenzae type b (Hib) booster vaccine (at 18 months of age). SETTING: Suburban community. INTERVENTIONS: Parents of the identified children were randomly assigned either to a group to receive a reminder notice of pending vaccinations or a control group that did not receive a notice at a ratio of 1:1. Immunization uptake was assessed eights weeks after the initial due date for vaccination. RESULTS: Information was obtained for 224 children in the MMR group and 227 children in the DPT-IPV-Hib booster group. MMR uptake within eight weeks of the due date was about 90% in both the test and control groups, probably because of publicity surrounding a local college-based measles outbreak. In the DPT-IPV-Hib group, reminder notices had no effect; the uptake rates within eight weeks of the due date were 73.7% to 75.2%. Delays in immunization resulted mostly from parents' scheduling problems and provider-recommended delays. More than half of the parents whose child had delayed immunization did not recall receiving the reminder notice. CONCLUSIONS: Mailed reminders did not increase on-time immunization rates in the second year of a child's life. A telephone call or a more memorable reminder notice may be better suited to catch the attention of parents.

Serologic responses to measles, mumps, and rubella (MMR) vaccine in healthy infants: failure to respond to measles and mumps components may influence decisions on timing of the second dose of MMR.

Measles, mumps, and rubella-specific IgG antibodies were evaluated in 134 healthy infants routinely immunized with trivalent live attenuated measles-mumps-rubella (MMR) vaccine at one year of age. Blood samples were collected just before, and at 1, 3, and 12 months after MMR. Specific IgG was measured by commercial enzyme immunoassays. Before vaccination, 98.5%, 99.2%, and 98.5% of the infants tested were seronegative for measles, mumps, and rubella, respectively. One year after MMR, 16.4% and 22.4% of vaccinees lacked demonstrable antibody to measles and mumps while none were found to be seronegative for rubella. Response profile analysis revealed primary failure rates of 12.1% (measles) and 8.6% (mumps) while 4% (measles) and 13.8% (mumps) of the infants responded initially but became seronegative within one year. These observations suggest that earlier administration (at age 18 months) of the second dose of MMR may be more desirable than revaccination at school entry.

[Use of low doses of bromocriptine in chronic schizophrenia resistant to neuroleptics. A preliminary study]. / Utilisation de faibles posologies de bromocriptine dans la schizophrénie chronique résistante aux neuroleptiques. Une étude préliminaire.

In this work, we report the efficiency of bromocriptine (1.25 and 2.5 mg/day) in 9 neuroleptic resistant chronic schizophrenics. Following an initial four-week placebo period, the subjects successively received bromocriptine (1.25 mg/day), placebo and bromocriptine (2.5 mg/day). The 2 bromocriptine treatments significantly improved the global psychiatric symptomatology and different scores and factors related to the more specific schizophrenic symptomatology. An escape phenomenon seems to occur during the 4th week of the first bromocriptine treatment (1.25 mg/day) but is not observed with the second treatment (2.5 mg/day). All patients improved.

[Tardive dyskinesia. After more than 2 decades]. / Les dyskinésies tardives. Après plus de deux décennies.

The clinical aspects of tardive dyskinesia are describe, outlining the difficulties and the limits encountered by the clinician. The tools for its evaluation are reviewed, as well the epidemiology data and the current neuropathological hypothesis.

[Lithium, pregnancy and breast feeding]. / Lithium, grossesse et allaitement.

Due to its teratogenic potential and its passage in the maternal milk, the administration of lithium during pregnancy and post-partum, if breast-feeding is contemplated, raises specific issues. The kinetics of lithium during pregnancy is reviewed, as well as its influence on the foetus during this period and during breast-feeding. Its teratogenicity affects particularly the cardiovascular system, the Ebstein's anomaly being the most typical and frequent malformation. As a general rule, the administration of lithium should be avoided during pregnancy, at least during the first trimester. However, pregnancy and breast-feeding do not represent an absolute contraindication for the continuation of lithium therapy if it is deemed necessary, in spite of the risks that can be incurred and of which the patient should be informed.

[Neuropsychology of a psycho-organic syndrome caused by idiopathic hypoparathyroidism. Apropos of a case]. / Neuropsychologie d'un syndrome psycho-organique secondaire à une hypoparathyroïdie idiopathique. A propos d'un cas.

A case of organic psychosis secondary to an idiopathic hypoparathyroidism with intracranial calcifications affecting the basal ganglia and the cortico-medullary junction is described. The results of the skull X-ray, cerebral TACO and nuclear magnetic resonance imaging analyses are presented, as well as a battery of neuropsychological tests. In spite of the extensive calcifications found, deficits on the neuropsychological tests were minimal or non-existent; possible explanations of this discrepancy are discussed.

[Clinical aspects of tardive dyskinesias induced by neuroleptics]. / Aspects cliniques des dyskinésies tardives induites par les neuroleptiques.

Initially, the reality of the existence of tardive dyskinesia raised some controversy, but rapidly this syndrome was recognized as a complication arising from usually long-term administration of neuroleptics. These extrapyramidal abnormal movements represent an important problem due to their prevalence, their potential irreversibility, their complex and still disputed physiopathologic mechanism, the absence of specific and generally effective treatment, and more recently the medico-legal problems entailed. At first, it was believed that these dyskinetic movements, of various intensity, were localized only at the oro-facial area (face, tongue, maxillary), or consisted of limited or generalized choreo-athetosic movements, or were a mixture of both types of movements. However, digestive and respiratory tardive dyskinesia also occur. Tardive dyskinesia can develop insidiously during neuroleptic treatment, or appear when this medication is decreased or ceased. It can coexist with parkinsonian signs. Age (over 50) and gender (female) appear to be risk factors. Other types of tardive syndromes associated with neuroleptic administration have been reported, such as tardive akathisia, tardive dystonia and a tardive Tourette-like syndrome. Involuntary movements resembling tardive dyskinesia can be observed in elderly individuals who never received neuroleptic medication. With respect to the rabbit syndrome, a rapid tremor of the perioral area, with a rhythmicity similar to the parkinsonian tremor, it is clearly different from tardive dyskinesia. It is essential to detect as precociously as possible tardive dyskinesia. The diagnosis is sometimes difficult and even if the clinical features seem pathognomonic of tardive dyskinesia, it is nevertheless important to establish a differential diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

[The treatment of psychopathologic disorders associated with tardive dyskinesias]. / Traitement des troubles psychopathologiques associés aux dyskinésies tardives.

Tardive dyskinesia, an extrapyramidal syndrome consisting of involuntary hyperkinetic movements, is a serious side effect induced by the administration, usually on a long-term basis, of neuroleptic therapy mostly for psychotic disorders. Therefore, psychopathologic disturbances, florid or residual may coexist with the appearance and persistence of tardive dyskinesia. Thus, the exact nature of the psychopathology observed with the presence of tardive dyskinesia and its origin is difficult to delineate and to assess. Indeed, the psychopathological findings observed can possibly originate from the initial psychiatric disorder itself from the intrinsic effect of the neuroleptic medication on psychic processes, may be specifically related to tardive dyskinesia, or be the result of all these factors. Cognitive, thymic or psychotic disturbances have been closely associated with tardive dyskinesia, but their systematic studies is still scarce. Based on these findings, some tentative therapeutic considerations will be outlined, keeping in mind that exact nature and origin of these disturbances still remains to be elucidated, that no really specific and generally effective treatment of tardive dyskinesia has been found.