Gwenaelle Diene

Bio: Gwenaelle Diene is an academic researcher from Boston Children's Hospital. The author has contributed to research in topics: Population & Ghrelin. The author has an hindex of 22, co-authored 42 publications receiving 1363 citations. Previous affiliations of Gwenaelle Diene include French Institute of Health and Medical Research & University of Toulouse.

Review of 64 cases of death in children with Prader-Willi syndrome (PWS)

Abstract: Several deaths have been reported in children with Prader-Willi syndrome (PWS) following treatment with growth hormone (GH). We collected all of the reports of deaths in PWS children, both in treatment and non-treatment groups, analyzed the causes of the death and compared the two groups. We conducted an exhaustive search for reports using bibliographic databases, toxicology pharmacovigilance databases, and personal communications. Sixty-four PWS children (42M/22F) aged from a few days to 19 years were identified, 28 received GH treatment. Our results show that respiratory disorders were the most common cause of death (respiratory insufficiency or infections) which were reported in 61% of the children (68% in GH-treated and 55.5% in -untreated patients). We found no significant differences in gender, prevalence of obesity or prevalence of sleep apnea, between the patients treated with GH and the untreated patients. Nevertheless, most of the deaths in GH-treated children (75%) occurred during the first 9 months after the initiation of GH treatment. Our analysis shows the high frequency of respiratory infections in both GH-treated and -untreated PWS children. The first 9 months of GH treatment seems to be a high-risk period emphasizing the need for comprehensive care before and during GH treatment.

Endocrine disorders in children with Prader-Willi Syndrome - data from 142 children of the French database.

Abstract: Aim: The first results from the French National Prader-Willi pediatric database in a cohort of 142 children aged 0.2–18.8 years are reported. This database gathers information about

Hyperghrelinemia precedes obesity in Prader-Willi syndrome.

Abstract: Background: High plasma ghrelin levels have been reported in Prader-Willi syndrome (PWS). However, little is known about plasma ghrelin in these children during the first years of life characterized by a failure to thrive. Objective: The objective of the study was to investigate total plasma ghrelin levels in children with PWS and controls from 2 months to 17 years. Subjects and Methods: Forty children with PWS [24 boys, 16 girls, median age 3.6 yr, median body mass index (BMI) Z-score 0.3] were compared with 84 controls (57 boys, 27 girls, median age 4.2 yr median BMI Z-score 0.1). Children were then divided into two groups according to age and GH treatment. Results: Median plasma ghrelin levels were significantly higher in children with PWS, compared with controls at any age (568 vs. 173, P < 0.0001) and decreased with age in both groups (P < 0.0001). In the whole group of PWS, we found an inverse relationship between ghrelin and BMI Z-score, insulin, homeostasis model assessment insulin resistance inde...

The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader-Willi Syndrome.

Abstract: BACKGROUND AND OBJECTIVES: Patients with Prader–Willi syndrome (PWS) display poor feeding and social skills as infants and fewer hypothalamic oxytocin (OXT)-producing neurons were documented in adults. Animal data demonstrated that early treatment with OXT restores sucking after birth. Our aim is to reproduce these data in infants with PWS. METHODS: We conducted a phase 2 escalating dose study of a short course (7 days) of intranasal OXT administration. We enrolled 18 infants with PWS under 6 months old (6 infants in each step) who received 4 IU of OXT either every other day, daily, or twice daily. We investigated the tolerance and the effects on feeding and social skills and changes in circulating ghrelin and brain connectivity by functional MRI. RESULTS: No adverse events were reported. No dose effect was observed. Sucking assessed by the Neonatal Oral-Motor Scale was abnormal in all infants at baseline and normalized in 88% after treatment. The scores of Neonatal Oral-Motor Scale and videofluoroscopy of swallowing significantly decreased from 16 to 9 (P CONCLUSIONS: OXT is well tolerated in infants with PWS and improves feeding and social skills. These results open perspectives for early treatment in neurodevelopment diseases with feeding problems.

Oxytocin may be useful to increase trust in others and decrease disruptive behaviours in patients with Prader-Willi syndrome: a randomised placebo-controlled trial in 24 patients

Abstract: Background: Prader-Willi syndrome (PWS) is a complex neurodevelopmental genetic disorder with hypothalamic dysfunction, early morbid obesity with hyperphagia, and specific psychiatric phenotypes including cognitive and behavioural problems, particularly disruptive behaviours and frequent temper outbursts that preclude socialization. A deficit in oxytocin (OT)-producing neurons of the hypothalamic paraventricular nucleus has been reported in these patients. Methods: In a double-blind, randomised, placebo-controlled study, 24 adult patients with PWS received a single intranasal administration of 24 IU of OT or placebo and were tested 45 min later on social skills. Behaviours were carefully monitored and scored using an in-house grid as follows: over the two days before drug administration, on the half-day following administration, and over the subsequent two days. All patients were in a dedicated PWS centre with more than ten years of experience. Patients are regularly admitted to this controlled environment. Results: Patients with PWS who received a single intranasal administration of OT displayed significantly increased trust in others (P = 0.02) and decreased sadness tendencies (P = 0.02) with less disruptive behaviour (P = 0.03) in the two days following administration than did patients who received placebo. In the half-day following administration, we observed a trend towards less conflict with others (p = 0.07) in the OT group compared with the placebo group. Scores in tests assessing social skills were not significantly different between the two groups. Conclusions: This study needs to be reproduced and adapted. It nevertheless opens new perspectives for patients with PWS and perhaps other syndromes with behavioural disturbances and obesity.

Radiographic Atlas of Skeletal Development of the Hand and Wrist

Abstract: The Brush Foundation studies on human growth and development, begun in 1931 and terminated in 1942, have been intensively reviewed and studied by Dr Greulich and Miss Pyle in the formulation of this Radiographic Atlas of Skeletal Development of the Hand and Wrist Serial radiographs of from 2 to 20 hand-films made at successive examinations of each of 1000 boys and girls made up the radiographic material Standards were selected that were judged to be the most representative of the central tendency or anatomic mode of each chronologic age group from birth through 18 years

Obstructive sleep disordered breathing in 2- to 18-year-old children: diagnosis and management.

Abstract: This document summarises the conclusions of a European Respiratory Society Task Force on the diagnosis and management of obstructive sleep disordered breathing (SDB) in childhood and refers to children aged 2-18 years. Prospective cohort studies describing the natural history of SDB or randomised, double-blind, placebo-controlled trials regarding its management are scarce. Selected evidence (362 articles) can be consolidated into seven management steps. SDB is suspected when symptoms or abnormalities related to upper airway obstruction are present (step 1). Central nervous or cardiovascular system morbidity, growth failure or enuresis and predictors of SDB persistence in the long-term are recognised (steps 2 and 3), and SDB severity is determined objectively preferably using polysomnography (step 4). Children with an apnoea-hypopnoea index (AHI) >5 episodes·h(-1), those with an AHI of 1-5 episodes·h(-1) and the presence of morbidity or factors predicting SDB persistence, and children with complex conditions (e.g. Down syndrome and Prader-Willi syndrome) all appear to benefit from treatment (step 5). Treatment interventions are usually implemented in a stepwise fashion addressing all abnormalities that predispose to SDB (step 6) with re-evaluation after each intervention to detect residual disease and to determine the need for additional treatment (step 7).

Recommendations for the Diagnosis and Management of Prader-Willi Syndrome

Abstract: Objective: The objective of the study was to provide recommendations for the diagnosis and management of Prader-Willi syndrome throughout the life span to guide clinical practice. Participants: An open international multidisciplinary expert meeting was held in October 2006 in Toulouse, France, with 37 invited speakers and session chairs (see Acknowledgments) and 85 additional registered participants. The meeting was supported by an unrestricted educational grant from Pfizer. Evidence: Invited participants with particular expertise reviewed the published evidence base for their specialist topic and unpublished data from personal experience, previous national and international PWS conferences, and PWS Association clinical advisory groups. Sessions covered epidemiology, psychiatric, and behavioral disorders; breathing and sleep abnormalities; genetics; endocrinology; and management in infancy, childhood, transition, and adulthood. Consensus Process: This included group meetings including open discussion afte...