Refining the phenotypical and mutational spectrum of Taybi-Linder syndrome.

Taybi-Linder syndrome (TALS, OMIM 210710) is a rare autosomal recessive disorder belonging to the group of microcephalic osteodysplastic primordial dwarfisms (MOPD). This syndrome is characterized by short stature, skeletal anomalies, severe microcephaly with brain malformations and facial dysmorphism, and is caused by mutations in RNU4ATAC. RNU4ATAC is transcribed into a non-coding small nuclear RNA which is a critical component of the minor spliceosome. We report here four foetuses and four unrelated patients with RNU4ATAC mutations. We provide antenatal descriptions of this rare syndrome including unusual features found in two twin foetuses with compound heterozygosity for two rare mutations who presented with mild intrauterine growth retardation and atypical dysmorphic facial features. We also carried out a literature review of the patients described up to now with RNU4ATAC mutations, affected either with TALS or Roifman syndrome, a recently described allelic disorder.

[Initial training in psychotherapy for psychiatrists in France: results of a national survey]. / La formation aux psychothérapies des internes de psychiatrie en France : résultats d'une enquête nationale.

INTRODUCTION: According to a recent change in the French legislation (2010) regarding the regulation of the use of the title of "psychotherapist", psychiatrists are now allowed to use this title at the end of their training, without any additional training. However, various publications from 2000 have shown that there is no specific training in psychotherapy at a professional level during the training of psychiatrists. GOALS: To study the current situation of the Academic training of French psychiatrists in psychotherapy during their residency, their interest for these therapies, their level of satisfaction regarding their training, and the importance of additional private training programs. METHODOLOGY: A survey was carried out among residents in psychiatry from October 2010 until January 2011. An anonymous questionnaire covering five domains (academic teaching, psychoanalysis, extra-academic training, interest in a more developed model of training, supervision) was sent by the French Federative Association of Psychiatrists Trainees (AFFEP) to all French psychiatrist trainees, through their local trainee associations (n=26). RESULTS: The questionnaire was answered by 869 of the 1334 psychiatry residents (65%). The vast majority of the trainees reported being interested in psychotherapy, but 75% thought that their training in psychotherapy (psychoanalysis, cognitive-behavioral therapy [CBT] and systemic therapy) is insufficient. In 20 of the 26 universities, more than half of the trainees reported that their training was insufficient in the three fields; in four universities, more than half of the trainees were satisfied with at least one field. Yet, satisfaction rates were very different among universities: for example, 27% were satisfied with their psychoanalytic training in Paris and 87% in Strasbourg; 7% were satisfied with their CBT training in Strasbourg, but 65% in Nice. The vast majority (97%) believes that supervision about therapeutic relationship is necessary during residency rotations in the hospital. More than three quarters (78%) would like to have supervision at least twice a month. Yet, only 51% of respondents have such supervision. Once again, large disparities were observed between different Academies: for example 74% had supervision in Montpellier, but only 29% in Marseille. The vast majority (95%) of trainees would like a two-phase model of training (general theoretical teaching plus in-depth training in one or more methods), which is different to the current training model. CONCLUSION: Our results show a clear discrepancy between the importance of training in psychotherapy for psychiatrists, the interest of psychiatry students for these therapies, and the very high rate of dissatisfaction for the training received, as well as the rate of students supervised during their training period at the hospital. These results differ from what is observed in other countries, where satisfaction rates are much higher among students, and various psychotherapy training methods are proposed in a much more homogeneous manner. More research is required to understand the reasons for these difficulties with the psychotherapy training of psychiatrists in France, and to propose new models of training to improve this situation.

[Evaluation of hospital stays linkage quality to study health spatial variation. a feasibility study in three French regions]. / Évaluation de la qualité du chaînage des séjours hospitaliers pour l'étude des variations spatiales de santé à partir des données du PMSI. Étude de faisabilité dans trois régions françaises.

BACKGROUND: Since 2001, the French hospital stay databases (Programme de médicalisation des systèmes d'information, PMSI) have included a unique and anonymous identifier in order to cross-link discharge abstracts from a given patient, within and across hospitals. These data could be used to estimate prevalence for some diseases at a territorial level provided that linkage quality is good enough. Few morbidity data are available at this scale. This study analyzes the link between linkage quality and hospitalization rates in three French regions (Picardy, Brittany and Provence-Alpes-Côte d'Azur-Paca). METHODS: We studied short stays in medicine-chirurgical-obstetrical units for the 2004-2005 period (all stays, and stays with mention of cancer or asthma). To study linkage quality, the percentage of linkable stays (no error during the production of the anonymous identifier) was calculated at regional and territorial levels (areas used by regional health authorities). The interquartile range (IQR=third quartile-first quartile) of the percentage of linkable stays was calculated and the link between this percentage and standardized rates of people hospitalized at least once in 2004 or 2005 tested by Spearman correlation coefficients. RESULTS: For all stays, percentages of linkable stays were 94.4%, 96.6% and 97.0% in Picardy, Paca and Brittany respectively in 2004-2005. Geographical variation at the territorial level was higher in Picardy (IQR between 4 and 6) than in the two other regions (IQR between 1 and 2). The percentage of linkable stays was positively and significantly associated with the hospitalization rate for all stays and those with mention of cancer in Picardy only. CONCLUSION: According to these results, PMSI data earlier than 2006 should be used with precaution; linkage quality should be analyzed before making geographical or time comparisons of hospitalization rates. Comparisons cannot always be made. Other studies should be carried out in other regions, and to analyze recent trends in linkage quality.

Fetal right ventricular diverticulum with pericardial effusion: report of a new case treated by in utero pericardiocentesis.

Right ventricular diverticulum associated with pericardial effusion was diagnosed in a male fetus at 13 weeks of gestation. Screening for infectious, chromosomal, or structural disease was negative. Because there was concern about pulmonary hypoplasia, fetal pericardiocentesis was performed at 17 weeks of gestation. The pericardial fluid did not reaccumulate, and the diverticulum decreased and finally disappeared before the third trimester. The diverticulum could not be seen on the neonatal echocardiography scan performed on the full-term live baby, who was delivered vaginally. The child is doing well at 11 months of age. Given the good outcome of this case, in utero drainage should be considered in similar cases.

[Feto-maternal metabolism in human normal pregnancies: study of 73 cases]. / Métabolisme foeto-maternel au cours de grossesses humaines normales: étude de 73 cas.

From 73 normal pregnancies of gestational age between 17 and 41 weeks of gestation (WG), the concentrations of glucose, pyruvate and lactate, free fatty acids, ketone bodies (aceto-acetate and beta-hydroxybutyrate) and cholesterol were assessed on maternal venous blood (MVB) and umbilical venous blood (UVB), sampled by cordocentesis. The objective of this work was to study feto-maternal metabolism, as well as nutritional exchange between maternal blood and fetal blood during the second and third trimesters of pregnancy. Maternal and fetal glycemias, as well as maternal-fetal glucose concentration gradient, were found stable during the studied gestational period; maternal glucose is always higher than fetal glucose, with a mean concentration delta of 0.69+/-0.34 mmol/L. Maternal lactate level (1.26+/-0.38 mmol/L) is lower than fetal lactate level (1.48+/-0.46 mmol/L), whereas maternal blood pyruvate concentration (0.042+/-0.020 mmol/L) is higher than fetal blood pyruvate concentration (0.025+/-0.010 mmol/L). Consequently, mean lactate / pyruvate ratio is found twice lower in maternal blood (31.77+/-9.89) than in fetal blood (64.10+/-17.12). Free fatty acids concentration is approximately three times higher in maternal blood than in fetal blood (respectively 0.435+/-0.247 mmol/L and 0.125+/-0.046 mmol/L). Maternal venous aceto-acetate (0.051+/-0.042 mmol/L) and beta-hydroxybutyrate (0.232+/-0.270 mmol/L) concentrations are significantly lower than those in UVB (respectively 0.111+/-0.058 and 0.324+/-0.246 mmol/L) and the beta-hydroxybutyrate/aceto-acetate ratio is on average 1.7 times higher in MVB (4.75+/-2.5) than in UVB (2.82+/-1.18). Cholesterol concentration is significantly higher in maternal blood (6.26+/-1.40 mmol/L) than in fetal blood (1.66+/-0.34 mmol/L). Our results show the characteristics of oxidative metabolism of the fetus compared with that of the adult. Blood concentration in energy substrates, measured with glucose and free fatty acids levels, is low in UVB and suggests increased energy needs of the growing fetus. Mean high concentrations in aceto-acetate and beta-hydroxybutyrate in UVB, indicate probably fetal ketogenesis. UVB low cholesterolemia suggests high cholesterol consumption in the fetal compartment for cellular membrane synthesis and steroid biosynthesis.

[Biochemical profile of fetal blood sampled by cordocentesis in 35 pregnancies complicated by growth retardation]. / Etude biochimique du sang foetal prélevé par cordocentèse au cours de 35 grossesses compliquées de retard de croissance.

AIM OF THE STUDY: Intra-uterine growth retardation (IUGR) is a frequent pathology in obstetrics characterized by high heterogeneity. Fetal smallness is sometimes constitutional, but can also be accompanied by fetal distress and vital risks for the infant. In 35 pregnancies complicated by IUGR of different etiologies, we measured on fetal blood obtained by cordocentesis, biochemical variables characteristic of the fetuses' respiratory and metabolic status. The aim of the study was to identify the discriminative biological alterations, related to growth retardation and fetal distress. PATIENTS AND METHODS: The studied population includes 27 cases of severe IUGR, of gestational age 30,2+/-4,6 weeks of gestation (WG) (divided into 20 cases of isolated IUGR and 7 cases of IUGR associated with malformative syndrome), as well as 8 cases of moderate IUGR, of gestational age 26+/-4,5 WG; all fetuses had normal karyotypes. A group of 73 normal fetuses, of gestational age 26,3+/-5,7 WG, constituted a reference population. PH, pCO(2), bicarbonate concentration, pO(2) and SaO(2), as well as glucose, pyruvate, lactate, free fatty acids, aceto-acetate, beta-hydroxybutyrate and cholesterol concentrations were measured on umbilical venous blood (UVB). RESULTS: In case of severe but isolated growth retardation, UVB analysis showed the frequency of acid-base and gasometric disturbances: acidemia and hypoxemia (65% of cases), hypercapnia (60% of cases). Metabolic abnormalities were shown: decrease in glycemia (35% of cases), increase in pyruvatemia and lactatemia (40% of cases), increased free fatty acids serum concentration; a diminution of umbilical venous cholesterol level, the most frequent abnormality, can be seen in 70% of fetuses. In case of severe IUGR associated with malformative syndrome, UVB acid-base and metabolic changes were rarely seen; however, UVB cholesterol level is low in some cases. In case of growth retardation classified as moderate, modifications are relatively not frequent and essentially gasometric. CONCLUSION: In about 60% of cases of severe and isolated IUGR, there is a risk of fetal distress, related to an alteration of the transplacental transfer of respiratory gases and nutritional substrates; chronic fetal malnutrition can be involved, with an impact on the growth of the fetus. In case of IUGR associated with malformative syndrome, fetal smallness is probably a result of intrinsic fetal damage, without nutritional origin.

Planned vaginal delivery versus elective caesarean section in singleton term breech presentation: a study of 1116 cases.

OBJECTIVE: To compare neonatal and maternal morbidity and mortality between planned vaginal delivery and elective cesarean section for singleton term breech presentation. STUDY DESIGN: We studied retrospectively all deliveries of singleton breech presentations at term in the public Hospitals of Lyon between 1 January 1991 and 31 December 1995. To take only the effect of delivery on the fetus into account, we eliminated high risk pregnancies and fetal malformations. Fetal parameters were corrected perinatal mortality, Apgar score<7 at 1 and 5 min, umbilical cord arterial pH<7.15, neurological disorders, trauma and need for neonatal intensive care. Maternal parameters were mild, moderate and severe complications. RESULTS: Of the 1116 breech presentations, 702 (62.9%) underwent an elective caesarean section and 414 (37.1%) a planned vaginal delivery. In the latter group, 342 (30.6%) had a vaginal delivery and 72 (6.5%) a non-elective caesarean section. Infants for whom the vaginal route was planned were at higher risk of mortality and morbidity. There were 2 deaths in this group and none in the elective caesarean section group and all fetal parameters were poorer: more Apgar<7 at 5 min (RR: relative risk=3.05; 1.03-9.05), arterial pH<7.15 (RR=1.64; 1.11-2.43), intubations (RR=7.35; 2.10-25.6), neurological disorders, trauma (RR=4.24; 1.66-10.8), transfer to intensive care units (RR=3.23; 1.57-6.64). The overall maternal morbidity was lower in the planned vaginal delivery group (RR=0.65; 0.44-0.94) but this was only because of less mild complications. The moderate and severe complications were the same in the two groups (RR=0.97; 0.59-1.57). CONCLUSIONS: Planned vaginal delivery in singleton term breech presentation increases the risk of death and of neonatal complications. Elective caesarean section increases the risk of only mild maternal complications. For these reasons, elective caesarean section should be preferred for singleton term breech presentations.

[Rubella in pregnancy. Management and prevention]. / Rubéole pendant la grossesse. Conduite à tenir et prévention.

DECLINING INCIDENCE: Between 1982 and 1994, the incidence of rubella infections during pregnancy in France declined form 45 to 9 cases per 100,000 births. The incidence of congenital rubella declined from 5 to 0.85 per 100,000 births. These results are the fruit of systematic vaccination of 1-year-old children in France. Eradication of congenital rubella has been achieved in Sweden and requires further efforts to be obtained in our country. SEROLOGY: Physicians must systematically check rubella serologies in all women desiring pregnancy and/or of reproductive age even if they have been vaccinated. Rubella serology must be checked in all pregnant women even if they were seropositive during a prior pregnancy. IN CASE OF EXPOSURE OR ERUPTION DURING PREGNANCY: Serology must be obtained as early as possible in case of suspected rubella infection during pregnancy with a second serology 3 weeks later. The IgM titre should be obtained in case of suspected exposure with significant rise in IgG in successive serologies, if specific IgG titre is elevated after an eruption, if the first serum sample was taken late after suspected exposure, and finally if a systematic serology early in pregnancy is positive after a previously negative serology. ANTENATAL DIAGNOSIS: PCR on amniotic fluid or fetal blood is indicated if a seroversion occurs before 18 weeks gestation. Therapeutic termination of pregnancy should be proposed if fetal infection is certain. After 18 weeks, there is nearly no risk for the fetus: an antenatal diagnostic sample is not required and ultrasound surveillance is sufficient.

[Acid-base equilibrium and oxygenation of the human fetus. Study of 73 samples obtained by cordocentesis]. / Equilibre acido-basique et oxygénation du foetus humain. Etude de 73 prélèvements obtenus par cordocentèse.

Acid-base state and oxygenation of fetal blood were evaluated in a group of 73 appropriate for gestational age fetuses between 17 and 41 weeks of gestation; fetal blood was obtained by cordocentesis. We measured, on umbilical venous blood, pH, pCO2, bicarbonates and total CO2, pO2 and percent oxygen saturation; we obtained following results: pH = 7.309 +/- 0.054; pCO2 = 5.99 +/- 0.85 kPa; HCO3 = 22.16 +/- 1.90 mmol/l; total CO2 = 22.53 +/- 1.97 mmol/l; pO2 = 6.02 +/- 1.68 kPa; SaO2 = 0.71 +/- 0.18. In comparison with adult normal values, our results report in fetuses a frequent state of mild and mixed acidosis (in about 80% of cases), rather gazeous; pH is significantly correlated with pCO2 (r = -0.799), moreover there is also a metabolic origin in acidosis. We observed progressive modifications of acid-base state and oxygenation in fetal blood with advancing gestational age: decrease of pH and pO2, increase of pCO2 and bicarbonates; these changes appear mainly from 35th week of gestation, except for bicarbonates, which increase regularly during gestational period we have studied. Fetal acid-base state may be explained by physiological differences due to fetal life conditions, in comparison with adult life conditions. Results obtained in this population of normal fetuses can be considered as reference values for studied parameters.

[Laparoscopic external iliac lymphadenectomy in the treatment of cancer of the cervix uteri]. / La lymphadénectomie iliaque externe per-coelioscopieque dans le traitement du cancer du col utérin.

OBJECTIVES: The aims of this study are to evaluate the feasibility of laparoscopic iliac external lymphadenectomy and to define current indications of this technique in pre-treatment staging of cervical carcinoma. MATERIAL AND METHOD: Forty seven patients with FIGO stages IA-IIIB invasive cervical cancer underwent transperitoneal laparoscopic iliac lateral lymphadenectomy prior to initiation of treatment. The mean length of operation was 115 min (35-180). An average of 14 nodes were retrieved from each patient (3-30). Percentage of complete removal was 96% in this study. The rate of complications was 6%, they were always minor. Today's most accepted indications concern: 1) FIGO IA2 stages with lymphovascular involvement or micro-invasion over 3mm, for which a simple resection of lesions can be performed if pN0. 2) Small FIGO IB stages where an exclusive vaginal enlarged colpo-hysterectomy can be performed for pN0. Other indications should not be performed for the moment except for therapeutical trials.

[Lysine-vasopressin in gynecologic surgery by the vaginal route. Hemodynamic study]. / La lysine-vasopressine dans la chirurgie gynécologique par voie basse. Etude hémodynamique.

OBJECTIVES: Vasoconstrictors are often used in gynaecology for vaginal surgery. Ornipressin was prohibited in France in 1990 and we studied the haemodynamic effect of a structural analogue marketed in France, lysine-vasopressin infused locally at the operative field. METHODS: Four haemodynamic parameters were evaluated in 7 patients undergoing surgery via the vaginal route under epidural anaesthesia (lidocaine 2%). Arterial pressure and heart rate were measured noninvasively and thoracic bioimpedance was used for measuring cardiac index and systemic vascular resistance. Baseline levels were obtained after induction of anaesthesia and positioning the patient. Five units of lysine-vasopressin diluted in 20 ml of 9/1000 saline solution were infused locally into the cervix. Haemodynamic measures were made for 15 minutes. RESULTS: Five minutes after infusion, there was a significant increase in systolic (+21 +/- 7%) and diastolic (+29 +/- 9%) arterial pressure (p < 0.05) (Mann and Whitney U test). There was a tendency for bradycardia which did not reach significance. The systemic arterial resistances were increased from 3080 +/- 178 to 4965 +/- 227 ohm/m3 with concomitant drom in systolic index from 2.6 +/- 0.3 to 1.6 +/- 0.11 min/m2. The observed haemodynamic effects were similar to those obtained with onipressin and corresponded to a sudden increase in post-charge. Cardiac tolerance was poor with a drop in systolic index to a level corresponding to a fall in cardiac inotropism and coronary blood flow. CONCLUSION: With this product, the patients are exposed to the same diseases and accidents described for ornipressin and thus should be used with extreme care, in adapted situations by competent experienced surgeons for patients without cardiovascular or cerebral diseases.

Comparison of the effects of different menstrual tampons on the vaginal epithelium: a randomised clinical trial.

The effects on the vaginal epithelium of three different menstrual tampons in normal conditions of use were studied in 41 women during the menstrual period. The vaginal epithelium was studied in a total of 123 cycles at a structural and ultra-structural level with colposcopy, vaginal smear and biopsy on TEM and SEM. One of the three tampons studied showed a lower level of abnormalities on colposcopy (36.6% vs. 56.1% vs. 68.3%), with an inverse correlation between the severity of the dryness and the quantity of blood absorbed by the tampon (4.2 g when the colposcopy was normal vs. 1.8 g in case of severe dryness). Cytology is not a good test for assessing the effects of tampons because of the high rate of acellular and uninterpretable samplings. The biopsy effects were defined according to their depth in the epithelium. The same tampon showed the lowest level in biopsy abnormalities. No correlation was found between severity of the colposcopy and biopsy results. Colposcopy can demonstrate the degree of severity of dryness or any other effect, but biopsy only confirms the effect and does not correlate the degree of severity. Materials and designs of tampons can play a role in reducing the drying effects to the vaginal epithelium.

[Mammary microcalcifications: is there a consensus on interpretation and management?]. / Les microcalcifications mammaires: existe-t-il un consensus sur l'interprétation et la conduite à tenir?

Twenty two view mammograms without magnification, with microcalcifications corresponding to non palpable breast lesions, were submitted to 23 experienced observers, either gynaecologists or radiologists. These mammograms consisted of 10 malignant lesions and 10 benign lesions; all of them underwent surgical procedures. The microcalcifications were graded and categorized into one of the four groups: malignant; suspect; slightly suspect; benign. One of the four options was proposed: biopsy; mammogram within 3 months; mammogram within 6 months; mammogram within a year. Twelve observers out of 23 have referred to a classification. The mammograms were assessed according to a consensus. The validity of that diagnostic test was studied in various clinical situations and the lack of homogeneity of the responses was quantified. In the trade-off situation between sensitivity and specificity (suspect or malignant considered as positive), sensitivity is 50% and specificity is 70%. Moreover, the responses are not homogeneous at all and this lack of homogeneity is found to be statistically significant, greater than by chance alone. The diagnosis of cancer is more frequently put forward by the radiologists. This study explains the low predictive value of non palpable microcalcifications undergoing surgical procedures: from 11.5 to 44% in the literature. Similarly, there is no agreement on the frequency of the follow-up for these microcalcifications when they do not lead to surgical procedures.

[The value of immunohistochemistry in the analysis of axillary node dissection]. / Apport de l'immuno-histochimie dans l'analyse des curages axillaires.

Immuno-histochemistry (IHC) was used and compared with Hemalum-Eosin-Safran (HES) in the analysis of the products of axillary lymphatic clearance in 42 women had breast cancer. In 32 patients who were negative by the HES test there was no lymph metastasis found by the IHC test in the 365 lymph nodes which were examined. In 3 out of 10 patients who were positive which the HES test 2 extra lymph node invasions were found, and one breach in the lymph node capsule that had not been diagnosed through HES testing were found. A review of the literature shows that the IHC test has never been show to be inferior to the HES test. The number of additional nodes that have been invaded varies between 0.9-11% in infiltrating canalicular carcinomas. The changes of the IHC test is greater in infiltrating lobular carcinomas. It varies between seven and 33%. Although the technique for using IHC is longer, it is easier to read the result and this method should be set up in current practice.