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.

Effect of swim intensity on responses to dynamic apnoea.

The aim of this study was to determine the influence of swim intensity on acute responses to dynamic apnoea. 9 swimmers performed one 50 m front crawl trial in four different conditions: at 400 m velocity (V400) with normal breathing (NB), at V400 in complete apnoea (Ap), at maximal velocity (Vmax) with NB and at Vmax in Ap. Peak heart rate (HRpeak), blood lactate concentration after exercise (Lacpost ex) and Borg rating of perceived exertion (RPE) were measured. Arterial oxygen saturation (SpO2) was monitored with a pulse oximeter at forehead level during and after exercise. In Ap, swimming at V400 induced a significantly lower HRpeak and Lacpost ex than swimming at Vmax whilst RPE and the kinetics of SpO2 were not different at V400 and at Vmax. The minimal value of SpO2 in Ap was reached 10 to 11 s after the end of V400 and Vmax (81.7 ± 10.1% and 84.4 ± 10.6%, respectively). Swimming a 50 m front crawl in Ap resulted in a large decrease in SpO2 which occurred only after the cessation of exercise. The higher duration of apnoea during submaximal exercise could explain why SpO2 and RPE reached the same values as for maximal exercise.​.

Xq28 duplication including MECP2 in six unreported affected females: what can we learn for diagnosis and genetic counselling?

Duplication of the Xq28 region, involving MECP2 (dupMECP2), has been primarily described in males with severe developmental delay, spasticity, epilepsy, stereotyped movements and recurrent infections. Carrier mothers are usually asymptomatic with an extremely skewed X chromosome inactivation (XCI) pattern. We report a series of six novel symptomatic females carrying a de novo interstitial dupMECP2, and review the 14 symptomatic females reported to date, with the aim to further delineate their phenotype and give clues for genetic counselling. One patient was adopted and among the other 19 patients, seven (37%) had inherited their duplication from their mother, including three mildly (XCI: 70/30, 63/37, 100/0 in blood and random in saliva), one moderately (XCI: random) and three severely (XCI: uninformative and 88/12) affected patients. After combining our data with data from the literature, we could not show a correlation between XCI in the blood or duplication size and the severity of the phenotype, or explain the presence of a phenotype in these females. These findings confirm that an abnormal phenotype, even severe, can be a rare event in females born to asymptomatic carrier mothers, making genetic counselling difficult in couples at risk in terms of prognosis, in particular in prenatal cases.

A series of 38 novel germline and somatic mutations of NIPBL in Cornelia de Lange syndrome.

Cornelia de Lange syndrome is a multisystemic developmental disorder mainly related to de novo heterozygous NIPBL mutation. Recently, NIPBL somatic mosaicism has been highlighted through buccal cell DNA study in some patients with a negative molecular analysis on leukocyte DNA. Here, we present a series of 38 patients with a Cornelia de Lange syndrome related to a heterozygous NIPBL mutation identified by Sanger sequencing. The diagnosis was based on the following criteria: (i) intrauterine growth retardation and postnatal short stature, (ii) feeding difficulties and/or gastro-oesophageal reflux, (iii) microcephaly, (iv) intellectual disability, and (v) characteristic facial features. We identified 37 novel NIPBL mutations including 34 in leukocytes and 3 in buccal cells only. All mutations shown to have arisen de novo when parent blood samples were available. The present series confirms the difficulty in predicting the phenotype according to the NIPBL mutation. Until now, somatic mosaicism has been observed for 20 cases which do not seem to be consistently associated with a milder phenotype. Besides, several reports support a postzygotic event for those cases. Considering these elements, we recommend a first-line buccal cell DNA analysis in order to improve gene testing sensitivity in Cornelia de Lange syndrome and genetic counselling.

Effect of oral glucocorticoid intake on autonomic cardiovascular control.

This study analyzed baroreflex sensitivity, heart rate and systolic blood pressure variabilities during an oral 1 week administration of prednisone. This study examined the hypothesis that prednisone might change both systolic blood pressure level and baroreflex sensitivity. Twelve physically active male subjects participated to a double-blind, randomized cross-over study consisting of two 1-week periods of treatment separated by a 4-week drug-free washout period: placebo (PLA) or prednisone (PRED). Trials were performed by each subject four times on the second (D2) and seventh (D7) day of each treatment period. ECG and blood pressure were continuously recorded to compute heart rate variability, systolic blood pressure variability and baroreflex sensitivity components with the smoothed pseudo Wigner Ville distribution and baroreflex analysis. Following D2 prednisone treatment, both HR (PLA: 60.8 ± 10.5 vs. PRED: 65.8 ± 9.1 beats min(-1), p = 0.008) and low frequency component of systolic blood pressure variability (D2: 3.09 ± 0.19 vs. D7: 2.34 ± 0.19, p < 0.041) increased whereas other components did not change. Over 7 days of treatment, LF-SBP amplitude increased (D2: 2.71 ± 0.89 vs. D7: 3.87 ± 0.6 mmHg, p = 0.037). A slight increase in both HR and LF-SBPV were observed suggesting a potential sympathetic cardiovascular stimulus. Although we found a significant effect of the 1-week prednisone treatment on heart rate and low frequency power of systolic blood pressure variability, we reported neither an increase in the systolic blood pressure level nor a decrease in the baroreflex sensitivity. Therefore, the fragility of our results cannot support a deleterious effect of 1-week administration of prednisone on the autonomic cardiovascular control which might be involved in cardiovascular diseases.

Time-course of prednisone effects on hormonal and inflammatory responses at rest and during resistance exercise.

Glucocorticoids are among the most commonly used drugs. They are widely administered for acute and chronic musculoskeletal pain, as well as for several other pain syndromes, although their therapeutic use is sometimes diverted for doping purposes. Their time-course effects on hormonal and inflammatory responses nevertheless remain poorly understood, both at rest and during exercise. We therefore studied the alterations induced by 1 week of prednisone treatment (60 mg daily) in recreationally trained male athletes after 2 days (i. e., acute) and 7 days (i. e., short-term). Hormonal (i. e., DHEA, DHEA-S, aldosterone, and testosterone) and pro- and anti-inflammatory markers (i. e., IL-6, IL-10, and IL-1ß) were investigated at rest and after resistance exercise. A significant decrease in DHEA and DHEA-S (p<0.01) without change in the DHEA/DHEA-S ratio, aldosterone, or testosterone was demonstrated after acute prednisone intake. A significant increment in IL-10 and a significant decrement in IL-6 (p<0.05) were also observed with prednisone both at rest and during exercise, without significant change in IL-1ß. Continued prednisone treatment led to another significant decrease in both DHEA and DHEA-S (p<0.05), whereas no change in the inflammatory markers was observed between days 2 and 7. Our data demonstrate that the anti-inflammatory effects of prednisone were maximal and stable from the beginning of treatment, both in rest and exercise conditions. However, hormonal concentrations continued to decline during short-term intake. Further studies are needed to determine the effects of hormonal time-course alterations with longer glucocorticoid treatment and the clinical consequences.

A French collaborative survey of 272 fetuses with 22q11.2 deletion: ultrasound findings, fetal autopsies and pregnancy outcomes.

OBJECTIVE: The 22q11.2 deletion (del22q11.2) is one of the most common microdeletions. We performed a collaborative, retrospective analysis in France of prenatal diagnoses and outcomes of fetuses carrying the del22q11.2. METHODS: A total of 272 fetuses were included. Data on prenatal diagnosis, ultrasound findings, pathological features, outcomes and inheritance were analyzed. RESULTS: The mean time of prenatal diagnosis was 25.6 ± 6 weeks of gestation. Most of the diagnoses (86.8%) were prompted by abnormal ultrasound findings [heart defects (HDs), in 83.8% of cases]. On fetal autopsy, HDs were again the most common disease feature, but thymus, kidney abnormalities and facial dysmorphism were also described. The deletion was inherited in 27% of cases. Termination of pregnancy (TOP) occurred in 68.9% of cases and did not appear to depend on the inheritance status. However, early diagnosis was associated with a higher TOP rate. CONCLUSION: This is the largest cohort of prenatal del22q11.2 diagnoses. As in postnatally diagnosed cases, HDs were the most frequently observed abnormalities. However, thymus and kidney abnormalities and polyhydramnios should also be screened for in the prenatal diagnosis of del22q11.2. Only the time of diagnosis appeared to be strongly associated with the pregnancy outcome: the earlier the diagnosis, the higher the TOP rate.

[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.

Therapeutic glucocorticoid administration alters the diurnal pattern of dehydroepiandrosterone.

Significant alteration in hypothalamic-pituitary-adrenal function has been demonstrated in patients after short-term glucocorticoid therapy, but its impact on the circadian rhythm of steroid hormones has never been investigated. This study examined the effects of short-term prednisone administration on the diurnal patterns of dehydroepiandrosterone (DHEA) and testosterone. Saliva samples were collected from 11 healthy, physically active, male volunteers for DHEA and testosterone analysis, as follows: every 4 h from 0800 to 2000 h on 2 control days without medication, and after 1 week of oral therapeutic prednisone treatment (60 mg daily) (days 0-3). Overall, a diurnal decline in the two steroid hormones was observed on the control days. After short-term glucocorticoid administration, DHEA concentrations were significantly decreased with a complete disappearance of the DHEA diurnal pattern, which lasted 2 days post-treatment. No glucocorticoid effect was observed for testosterone. The results indicate that short-term prednisone treatment affects the circadian pattern of saliva DHEA but not testosterone in healthy active volunteers. Further studies are necessary to determine whether this alteration in DHEA circadian pattern has clinical consequences in patients with chronic glucocorticoid therapy.

The diurnal patterns of cortisol and dehydroepiandrosterone in relation to intense aerobic exercise in recreationally trained soccer players.

Diurnal patterns of cortisol and dehydroepiandrosterone (DHEA) secretion, the two main peripheral secretory products of the hypothalamic-pituitary-adrenal neuroendocrine stress axis, have been well characterized in rest conditions but not in relation to physical exercise. The purpose of this investigation was therefore to determine the effects of an intense 90-min aerobic exercise on the waking diurnal cortisol and DHEA cycles on three separate days [without exercise, with morning exercise (10:00-11:30 h), and with afternoon exercise (14:00-15:30 h)] in nine recreationally trained soccer players. Saliva samples were collected at awakening, 30 min after awakening, and then every 2 h from 08:00 to 22:00 h. A burst of secretory activity was found for cortisol (p < 0.01) but not for DHEA after awakening. Overall, diurnal decline for both adrenal steroids was observed on resting and exercise days under all conditions. However, there was a significant increase in salivary cortisol concentrations on the morning-exercise and afternoon-exercise days at, respectively, 12:00 h (p < 0.05) and 16:00 h (p < 0.01), versus the other trials. This acute response to exercise was not evident for DHEA. The results of this investigation indicate that 90 min of intense aerobic exercise does not affect the circadian pattern of salivary adrenal steroids in recreationally trained athletes over a 16-h waking period, despite a transitory increase in post-exercise cortisol concentration. Further studies are necessary to determine whether these results are applicable to elite athletes or patients with cortisol or DHEA deficiency.

Hyperoxia does not accelerate quadriceps muscle deoxygenation kinetics at the onset of heavy exercise cycle.

AIM: The aim of this study was to determine whether an increase in O2 availability induces an alteration of the balance between O2 consumption ((V)O2) and O2 delivery ((Q)O2) at the muscle level. For that, we examined the effect of moderate hyperoxia on muscle deoxygenation kinetics at the onset of heavy-intensity cycling exercise. METHODS: Eight young male adults performed step transitions from 35 W to heavy-intensity exercise corresponding to a power output half-way between the first ventilatory threshold and (V)O2max in normoxia and in hyperoxia (FIO2=0.30). Muscle deoxygenation (HHb) and total hemoglobin (Hbtot) were monitored continuously by near-infrared spectroscopy. HHb data were fit with a mono-exponential model from the onset of exercise up to 90 seconds. RESULTS: Hyperoxia neither altered the delay before the increase in HHb (normoxia: 10.7±1.8 s vs. hyperoxia: 9.5±1.9 s; NS) nor the HHb mean response time (normoxia: 20.6±2.8 s vs. hyperoxia: 19.6±2.3 s; NS). Likewise, Hbtot was not different between normoxia and hyperoxia. CONCLUSION: These results indicate that moderate hyperoxia has no effect on muscle deoxygenation kinetics at the onset of heavy exercise. It suggests that muscle (V)O2 increases at the same rate than O2 delivery when O2 availability is enhanced.

[One-leg cycling aerobic training with the healthy leg in amateur soccer players after anterior cruciate ligament reconstruction]. / Entraînement en endurance à partir du membre inférieur sain chez des footballeurs amateurs opérés de ligamentoplastie de genou.

OBJECTIVE: To examine cardiorespiratory fitness changes in subjects having undergone knee surgery and to assess the benefits of one-leg cycling aerobic training program during the rehabilitation period. METHOD: Two groups of 12 patients took part in this study. The control group profited from a five weeks conventional rehabilitation in day hospital without cardiorespiratory training. The second group profited in supplement from a one-leg cycling aerobic training program with the valid leg. The subjects were trained for 21 min, by alternating 3 min at 70% and 3 min at 85% of VO(2 peak). They totaled 15 sessions spread over five weeks. The initial evaluation (T1) is carried out the first day of rehabilitation and the final evaluation (T2) at a distance within 35 days. The evaluation consisted in realizing a maximal graded tests starting from the valid leg. RESULTS: After five weeks of conventional rehabilitation, we record a reduction of peak power output (W(peak)), peak oxygen uptake (VO(2 peak)) and peak minute ventilation (VE(peak)), respectively of 11, 12 and 13% for the control group. On the other hand, in T2, the training group has on average identical maximum values and some of them increased (W(peak): +14%; VE(peak): +15%). The first and second ventilatory thresholds appear with higher intensities of exercises. CONCLUSION: After knee surgery, conventional rehabilitation does not limit cardiorespiratory deconditioning. One leg cycling appears to be an adapted method to stop the effects of hypoactivity.

Clinical, electrophysiological and genetic studies of two families with mutations in the GDAP1 gene.

Mutations in the gene for the ganglioside-induced-differentiation-associated-protein 1 on 8q21 were recently reported to cause autosomal recessive Charcot-Marie-Tooth sensorimotor neuropathy. We report a detailed clinical, electrophysiological and genetic study of two young patients harbouring missense GDAP1 mutations. The two patients presented severe neuropathy with an early onset. One of the mutations (Tyr279Cys) has never been hitherto reported. Electrophysiological investigations suggested a predominant axonal damage in both patients. Despite the similitude of the type of mutations and electromyographic features, the clinical course was different for the patients, highlighting the complexity of genotype/phenotype relationships among GDAP1 mutations.

[Does exercise therapy for chronic lower-back pain require daily isokinetic reinforcement of the trunk muscles?]. / Le réentraînement à l'effort de la lombalgie chronique nécessite-t-il un renforcement musculaire isocinétique quotidien du tronc?

OBJECTIVE: The goal of this study was to determine the benefits of a functional retraining programme (with or without daily isokinetic reinforcement of the trunk muscles) in patients with lower-back pain. METHOD: Two groups of 30 patients took part in the study. The control group (CG) underwent a four-week reconditioning program in a day hospital, whereas a second interventional group (IG) additionally performed daily isokinetic training of the trunk muscles. Three evaluations were carried out: before hospitalization (T1), immediately after hospitalization (T2) and three months postrehabilitation (T3). RESULTS: We observed an improvement in each parameter after rehabilitation, regardless of the group. A decrease in the DALLAS scores revealed a reduced impact of lower-back pain on the patients' lives. Pain experienced fell by 24%, analgesic treatment was significantly decreased (CG: -53%; IG: -56%), muscle endurance was improved (quadriceps: +30%, abdominal muscles: +20%, paraspinal muscles: +23%, quadratus lumborum: +33%) and the patients were more supple, as revealed by a decrease in the finger-to-ground distance (at T1, CG: 12.9+/-6.1cm; IG: 13.6+/-5.5 cm at T1; CG: 2.2+/-5.4 cm; IG: 2.8+/-5.1cm at T2). The sole difference for CG and IG at T2 resulted from an improvement in the performance of the trunk extensor muscles, which was significantly greater in the IG (CG: +14%; IG: +20%). Three months after rehabilitation, the benefits were still present for the two groups and, indeed, were even greater for certain parameters. CONCLUSION: Regardless of the protocol, the patients improved in both physical and psychological terms and these improvements were maintained over a short period, at least. Our results confirmed that one functional recovery programme is not superior to another for patients with lower-back pain.

Effect of high-intensity interval training and detraining on extra VO2 and on the VO2 slow component.

To examine the effect of 6-week of high-intensity interval training (HIT) and of 6-week of detraining on the VO2/Work Rate (WR) relationship and on the slow component of VO2, nine young male adults performed on cycle ergometer, before, after training and after detraining, an incremental exercise (IE), and a 6-min constant work rate exercise (CWRE) above the first ventilatory threshold (VT1). For each IE, the slope and the intercept of the VO2/WR relationship were calculated with linear regression using data before VT1. The difference between VO2max measured and VO2max expected using the pre-VT1 slope was calculated (extra VO2). The difference between VO2 at 6th min and VO2 at 3rd min during CWRE (DeltaVO2(6'-3')) was also determined. HIT induced significant improvement of most of the aerobic fitness parameters while most of these parameters returned to their pre-training level after detraining. Extra VO2 during IE was reduced after training (130 +/- 100 vs. -29 +/- 175 ml min(-1), P = 0.04) and was not altered after detraining compared to post-training. DeltaVO2(6'-3') during CWRE was unchanged by training and by detraining. We found a significant correlation (r2 = 0.575, P = 0.02) between extra VO2 and DeltaVO2(6'-3') before training. These results show that an alteration of extra VO2 can occur without any change in the VO2 slow component, suggesting a possible dissociation of the two phenomena. Moreover, the fact that extra VO2 did not change after detraining could indicate that this improvement may remain after the loss of other adaptations.

Effect of prior heavy exercise on muscle deoxygenation kinetics at the onset of subsequent heavy exercise.

This study examines the effect of prior heavy exercise on muscle deoxygenation kinetics at the onset of heavy-intensity cycling exercise. Ten young male adults (20 +/- 2 years) performed two repetitions of step transitions (6 min) from 35 W to heavy-intensity exercise preceded by either no warm-up or by a heavy-intensity exercise. VO2 was measured breath-by-breath, and muscle deoxygenation (HHb) and total hemoglobin (Hb(tot)) were monitored continuously by near-infrared spectroscopy. We used a two-exponential model to describe the VO2 kinetics and a mono-exponential model for the HHb kinetic. The parameters of the phase II VO2 kinetics (TD1 VO2, tau1 VO2 and A1 VO2) were unaffected by prior heavy exercise, while some parameters of local muscle deoxygenation kinetics were significantly faster (TD HHb: 7 +/- 2 vs. 5 +/- 2 s; P < 0.001, MRT HHb: 20 +/- 3 vs. 15+/- 4 s; P < 0.05). Blood lactate, heart rate and Hb(tot) values were significantly higher before the second bout of heavy exercise. These results collectively suggest that the prior heavy exercise probably increased muscle O2 availability and improved O2 utilization at the onset of a subsequent bout of heavy exercise.

Respiratory muscle oxygenation kinetics: relationships with breathing pattern during exercise.

This work aimed to investigate accessory respiratory muscle oxygenation (RMO(2)) during exercise, using near-infrared spectroscopy, and to study relationships between RMO(2) kinetics and breathing parameters. Nineteen young males (19.3 +/- 1.5 years) performed a maximal incremental test on a cycle ergometer. Changes in breathing pattern were characterized by accelerated rise in the breathing frequency (f (Racc)), plateau of tidal volume (V (Tplateau)) and inflection point in the V. (E)/V (T) relationship (V. (E)/V (T inflection)). First and second ventilatory thresholds (VT1 and VT2) were also determined. RMO (2) kinetics were monitored by NIRS on the serratus anterior. During exercise, all subjects showed reduced RMO (2) (deoxygenation) with a breakdown (B-RMO(2)) at submaximal workload (86 % .VO(2max)). .VO(2) corresponding to B-RMO (2) and to f (Racc), V (Tplateau), .V(E)/V(T inflection), or VT2 were not different. Relationships were found between the .VO(2) at B-RMO(2) and the .VO(2) at f (Racc) (r = 0.88, p < 0.001), V (Tplateau) (r = 0.84, p < 0.001), V. (E)/V (T inflection) (r = 0.58, p < 0.05) or VT2 (r = 0.79, p < 0.001). The amplitude of RMO(2) at maximal workload was weakly related to .VO(2max) (r = 0.58, p < 0.05). B-RMO (2) seems to be due to the change in breathing pattern and especially to the important rise in breathing frequency at the VT2 exercise level. Moreover, subjects who exhibit higher .VO(2max) also exhibit a higher decrease in respiratory muscle oxygenation during exercise.

Effect of prior exercise on the VO2/work rate relationship during incremental exercise and constant work rate exercise.

The disproportionate increase in VO2 ("extra VO2) reported at elevated intensity during incremental exercise (IE) might result from the same physiological mechanisms as the VO2 slow component observed during heavy constant work rate exercise (CWRE). Moreover, it has been demonstrated that prior heavy exercise can diminish the VO2 slow component. The aim of this study was to evaluate whether prior heavy exercise also alters the "extra VO2" during IE. Ten trained sprinters performed three tests on a cycle ergometer: Test 1 was an IE; Test 2 consisted of six minutes of a CWRE (90% of VO2max) followed by six minutes at 35 W and by an IE and Test 3 was composed of two CWRE of six minutes separated by six minutes of exercise at 35 W. For each IE, the slope and the intercept of the VO2/work rate relationship were calculated by linear regression using data before the first Ventilatory Threshold (pre-VT1 slope). The difference between VO2max measured and VO2max expected using the pre-LT slope was calculated (deltaVO2). We also calculated the difference between VO2 at min five and VO2 at min three during CWRE of Test 3 (deltaVO2(5' - 3')). VO2max was significantly higher than VO2exp during IE of Test 1 and Test 2. deltaVO2 during IE did not differ between Test 1 and Test 2 (+ 259 +/- 229 ml x min(-1) vs. + 222 +/- 221 ml x min(-1)). During Test 3, six subjects achieved five minutes of exercise during the second CWRE and deltaVO2(5' - 3') was significantly decreased during the second CWRE (338 +/- 65 ml x min(-1) vs. 68 +/- 98 ml x min(-1), n = 6). These results demonstrate that the amplitude of the "extra VO2"during IE was not affected by prior exercise, whereas the slow component of VO2 evaluated by deltaVO2(5' - 3') during CWRE was lowered. This implies that prior exercise does not have the same effect on the slow component of VO2 and on the "extra VO2". Therefore we were unable to demonstrate a relationship between the VO2 slow component and the extra-VO2 phenomenon during IE.

Isodicentric Yp: prenatal diagnosis and outcome in 12 cases.

OBJECTIVES: 1. To present the prenatal cytogenetic findings and postnatal outcome of 12 cases with an isodicentric chromosome composed of the short arm of the Y chromosome.2. To review the literature and provide recommendations for cytogenetic analysis and counseling. METHODS: Prenatal and postnatal cytogenetic data and clinical findings of isodicentric Yp ascertained in six institutions were gathered and reviewed. RESULTS: Nine of the twelve cases were referred for advanced maternal age (AMA), one of which was a twin pregnancy with one twin having an increased nuchal translucency measurement. The remaining cases were referred owing to a family history of hemophilia and an abnormal maternal serum screen, respectively. Nine of these pregnancies resulted in the birth of a normal-appearing male infant with subsequent normal growth and psychomotor development. Follow-up ranged from birth to 7 years. In two cases, the pregnancy was terminated and the fetuses showed male external genitalia. In the case ascertained because of an increased nuchal translucency measurement, the prenatal diagnosis of 45,X was made. At birth, there were ambiguous genitalia, and postnatal cytogenetic studies found an isodicentric Yp. In 11 of the 12 cases, mosaicism was present. CONCLUSION: Our cases show that the prenatal finding of an isodicentric Yp, with or without 45,X mosaicism, is compatible with normal male phenotype in most cases, particularly in the absence of other anomalies. To ensure accuracy in cytogenetic reporting and prenatal counseling, the identification of a structurally abnormal or small Y chromosome, either alone or in the presence of 45,X colonies, should be followed immediately by confirmatory molecular cytogenetic investigations as well as by ultrasound determination of the phenotypic sex of the fetus.

[Adrenal hypoplasia congenita: four new cases in children]. / Hypoplasie congénitale des surrénales : à propos de quatre observations.

Adrenal hypoplasia congenita (AHC) is an extremely uncommon disease of early onset. This condition can be lethal in the absence of adapted treatment. Some of these diseases are related to changes in the gene DAX1 that encodes a member of the superfamily of hormone nuclear receptors. It is a transcriptional repressor that is central in the morphogenesis of the adrenals and the gonadic differentiation. Here we report on four cases of X- linked AHC. In the first two familial cases, mutations were identified and mothers were heterozygotes. Abnormally low levels of estriol were evidenced during the pregnancy leading to an early diagnosis and adapted care of the affected male neonates. These children are doing well with a 21-and 20 months follow-up with hormone replacement at the present time. The two last cases corresponded to a contiguous gene syndrome associating AHC to glycerol-kinase deficiency that was revealed respectively at six days and seven years of age by acute adrenal insufficiency.