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OBJECTIVE: To evaluate the reliability of maximal static strength measurements of five arm muscle groups and of strength ratios (paretic/non-paretic) in subjects with poststroke hemiparesis. DESIGN: The generalizability theory was used to estimate the reliability coefficients and standard errors of measurement of maximal strength for various combinations of trials and sessions and of the strength ratios for one and two sessions. Grip maximal voluntary force and/or maximal voluntary torques exerted by flexor and extensor muscles at both the elbow and shoulder joints were measured in 17 subjects with poststroke hemiparesis. Multiple trials were performed by subjects during two sessions. SETTING: Rehabilitation centre. SUBJECTS: A convenience sample of 17 subjects with poststroke hemiparesis. RESULTS: The reliability coefficients for the strength measurements were in the range of 0.81-0.97 with standard errors of measurement accounting for 4% to 20% of the group means. For the strength ratios, the coefficients of generalizability ranged from 0.76 to 0.95 with standard errors of measurement equal to 6% to 19% of the group means. CONCLUSIONS: The maximal strength measurements of the arms in subjects with hemiparesis are reliable. The strength ratios are also reliable and can be used to quantify strength impairment. [ABSTRACT FROM AUTHOR]

Background: Chronic low back pain (CLBP) is a major economic and social problem worldwide. Despite the variety of recommended treatments, long-term self-management of this condition is complex and requires the development of innovative interventions. Mobile health (mHealth) technologies hold great promise for the management of chronic pain, particularly to support physical activity. However, their implementation is challenged by a lack of user compliance and limited engagement, which may be due to insufficient consideration of the needs of potential users during development., Objective: This study aims to explore the needs of people with CLBP and health care professionals regarding mHealth technologies to support self-managed physical activity, and to delineate design recommendations based on identified needs., Methods: A participatory study was conducted using a 3-phase, user-centered design approach: needs investigation with a group of experts in a workshop (phase 1), needs exploration with end users in focus groups (phase 2), and validation of needs using Delphi questionnaires followed by the development of a set of recommendations (phase 3)., Results: A total of 121 people with CLBP, expert patients, health care professionals, rehabilitation researchers, and biomechanical engineers participated in this study. The results indicated how technology could help people with CLBP overcome their difficulties with managing physical activity. Specific needs were formulated concerning device objectives, expected strategies, functionalities, technical features, conditions of use, and potential facilitators and barriers to use. These needs were validated by consensus from the potential end users and translated into design recommendations., Conclusions: This study provides design recommendations for the development of an mHealth device specifically adapted for people with CLBP., (©Mathilde Berger, Anne Deblock-Bellamy, Laurence Chèze, Thomas Robert, Julie J Desrosiers, Guillaume Christe, Anne Martine Bertrand. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 07.11.2024.)

Purpose: Accelerometers can be used to objectively measure physical activity. They could be offered to people with chronic low back pain (CLBP) who are encouraged to maintain an active lifestyle. The aim of this study was to examine the use of accelerometers in studies of people with CLBP and to synthesize the main results regarding the measurement of objective physical activity., Methods: A scoping review was conducted following Arksey and O'Malley's framework. Relevant studies were collected from 4 electronic databases (PubMed, Embase, CINHAL, Web of Science) between January 2000 and July 2023. Two reviewers independently screened all studies and extracted data., Results: 40 publications out of 810 citations were included for analysis. The use of accelerometers in people with CLBP differed across studies; the duration of measurement, physical activity outcomes and models varied, and several limitations of accelerometry were reported. The main results of objective physical activity measures varied and were sometimes contradictory. Thus, they question the validity of measurement methods and provide the opportunity to discuss the objective physical activity of people with CLBP., Conclusions: Accelerometers have the potential to monitor physical performance in people with CLBP; however, important technical limitations must be overcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Berger, Bertrand, Robert and Chèze.)

Background. Questionnaires measuring occupational balance have been created in recent years, but those available in French are limited. Purpose. This study aimed to translate and transculturally adapt the Occupational Balance Questionnaire and to examine the internal consistency, test-retest reliability and convergent validity of the French version. Methodology. A cross-cultural validation was conducted with adults in Quebec ( n  = 69) and in French-speaking Switzerland ( n  = 47). Results. Internal consistency was good in both regions (α > 0.85). Test-retest reliability was satisfactory in Quebec (ICC = 0.629; p  < 0.001), but a significant difference was found between the two measurement times in French-speaking Switzerland. Significant associations were found between the results of the Occupational Balance Questionnaire and those of the Life Balance Inventory (Quebec, r  = 0.47; French-speaking Switzerland, r  = 0.52). Implications. These initial results support the use of the OBQ-French in the general population of two French-speaking regions.

Aims: The Little Developmental Coordination Disorder Questionnaire (LDCDQ) is a parental questionnaire designed to identify preschool children at risk of Developmental Coordination Disorder (DCD). This study aimed to translate and cross-culturally adapt the LDCDQ for French European informants (Little Developmental Coordination Disorder Questionnaire-French European [LDCDQ-FE]) and to undertake a pilot examination of its psychometric properties on a French sample., Methods: A thorough process of cultural adaptation was completed. The psychometric properties were examined with a sample of 154 French children aged to 5y11m (control = 121; clinically referred = 33). A sub-group of 34 children was assessed using the MABC-2 to measure convergent validity., Results: Principal component analysis demonstrated a four-component structure, accounting for 67.5% of the variance. Internal consistency was acceptable to good ( α  = 0.74-0.89). Significant correlation between the LDCDQ-FE and the MABC-2 total scores showed convergent validity. Discriminant validity was supported by significant score differences between the clinically referred and a matched control sub-group. Using ROC curves, a cutoff of 67 was proposed for a sensitivity of 81.3% and a specificity of 77.8%., Conclusions: Results show initial evidence of the psychometric properties of the LDCDQ-FE and are encouraging of its use to identify young preschoolers at risk for DCD. In future studies, the test-retest reliability should be investigated, and study sample sizes expanded.

Early adiposity rebound (EAR) predicts paediatric overweight/obesity, but current approaches do not consider both the starting point of EAR and the BMI trajectory. We compared the clinical characteristics at birth, age 3-5 and 6-8 years of children, according to the EAR and to its type (type A/type B-EAR). We assessed the children's odds of being classified as overweight/obese at age 6-8 years, according to the type of EAR as defined at age 3-5 years. As part of this two-wave observational study, 1055 children were recruited and examined at age 3-5 years. Antenatal and postnatal information was collected through interviews with parents, and weight and height from the health records. Type A and type B-EAR were defined in wave 1 according to the BMI nadir and the variation of BMI z-score between the starting point of the adiposity rebound and the last point on the curve. At 6-8 years (wave 2), 867 children were followed up; 426 (40·4 %) children demonstrated EAR. Among them, 172 had type A-EAR, higher rates of parental obesity (P < 0·05) and greater birth weight compared with other children (P < 0·001). Odds for overweight/obesity at 6-8 years, when adjusting for antenatal and postnatal factors, was 21·35 (95 % CI 10·94, 41·66) in type A-EAR children and not significant in type B-EAR children (OR 1·76; 95 % CI 0·84, 3·68) compared with children without EAR. Classification of EAR into two subtypes provides physicians with a reliable approach to identify children at risk for overweight/obesity before the age of 5 years.

Background: The nine French regional health networks for the prevention and care of paediatric obesity offer a 2-year program of multidisciplinary primary care (medical, dietetical, psychological, adapted physical activity) based on multicomponent lifestyle interventions., Objectives: To assess the short-term and long-term impact of care management., Methods: The impact of the multidisciplinary care was assessed by changes in the body mass index (BMI) Z score during the period of the care, and at least 2 years after the end. Anthropometric data were collected at baseline and at the end of the care either through a digital medical file or through direct phone contacts with the referring. Long-term outcomes were assessed through studies relative to post follow-up evaluation., Results: At the end of the period of the care in a network, 72.9% of 6947 children had decreased their BMI Z score from 3.6 ± 1.0 DS at baseline to 3.3 ± 1.1 DS at the end. The four studies relative to long-term evaluation showed a pursuit of the decrease of BMI Z score during the 5.1 years after the beginning of the care., Conclusions: The care provided by regional French networks for prevention and care of paediatric obesity induce a reduction of BMI that continues afterwards., (© 2019 World Obesity Federation.)

Background: The Developmental Coordination Disorder Questionnaire'07 (DCDQ'07) is a parent-report measure to identify children at risk for Developmental Coordination Disorder (DCD). We developed a French version of the DCDQ'07 (DCDQ-FE) that has shown excellent inter-language reliability (intraclass correlation coefficient (ICC) = 0.91) and is culturally relevant for use in European countries. The aims of this study were to examine the internal consistency, test-retest reliability, construct validity of the Developmental Coordination Disorder Questionnaire-French European (DCDQ-FE), as well as establish a cut-off score., Methods: The psychometric properties of the DCDQ-FE were examined with a clinical group of 30 children (mean age: 9.4 years, SD = 2.6) and a control group of 43 children (mean age: 9.1 years, SD = 2.4). Their parents (n = 73) filled out the DCDQ-FE at a first sitting and 70 of them filled it out 38 days later in average for test-retest reliability. The children were assessed using the Movement Assessment Battery for Children-2 (MABC-2) so as to measure the convergent validity of the DCDQ-FE. The cut-off score was determined with an additional sample of 42 children according to scores on the MABC-2 (≥ 16th percentile) (n = 115)., Results and Implications: Internal consistency of the DCDQ-FE was excellent (Cronbach's alpha = 0.96) and test-retest reliability was good (ICC = 0.956) with no differences between scores obtained at the two sittings (p > 0.05). Differences in scores between children in the clinical and control groups (Z = -6.58, p < 0.001) provide evidence of construct validity. The correlation obtained between DCDQ-FE and MABC-2 scores (Spearman's rho correlation coefficient = 0.802, p < 0.001) supports convergent validity. Using a cut-off of 56, overall sensitivity and specificity were 85.0% and 81.6% respectively (area under the curve = 0.896). The DCDQ-FE is a reliable and valid questionnaire for detecting children who are at risk for DCD in a European-French population of children aged 5 to 15 years old., Competing Interests: The authors have declared that no competing interests exist.

Background: We aimed to evaluate whether pre and perinatal education of pregnant women would reduce childhood overweight., Methods: Four French centers included women at ≤21 gestational weeks (GWs) with body mass index (BMI) >25 kg/m 2 before pregnancy. Patients were randomized to a control group (routine care including at least one dietary visit) or an intervention group (2 individuals (26 and 30 GW) and 4 group sessions (21, 28, 35 GW, 2 months postpartum)) aimed at educating the future mother regarding infant and maternal nutrition. The primary objective was to reduce post-natal excessive weight gain in the infant from birth to 2 years (NCT00804765). This project was funded by a grant from the National Programme for Hospital Research (PHRC-2007 French Ministry of Health)., Results: We included 275 women (BMI: 32.5 kg/m 2 ). The rate of post-natal excessive weight gain was similar in the intervention (n = 132) and control (n = 136) groups by intention to treat (ITT: 59.1% vs 60.3% respectively, p = 0.84) in available data (AD, n = 206) and by per-protocol analysis (PP, n = 177). Two years after delivery, normalization of maternal BMI and number of infants with BMI < 19 kg/m 2 were not significantly different in the interventional group in ITT and in the control group. Although not significantly different in ITT, normalization of maternal BMI was more frequent in AD (n = 149: 12.9% vs 3.8%, p = 0.04) and 2-year-old infant BMIs were less likely to be >19 kg/m 2 in the intervention group in AD (n = 204: 0% vs 6.8%, p = 0.014) and PP (n = 176: 0% vs 6.4%, p = 0.03)., Conclusions: An education and nutritional counseling program for overweight women, starting after 3 months of gestation, did not significantly change post-natal excessive weight gain of infants or prevent overweight in mothers and children 2 years after delivery.

Context: LHX4 encodes a LIM-homeodomain transcription factor that is implicated in early pituitary development. In humans, only 13 heterozygous LHX4 mutations have been associated with congenital hypopituitarism., Objective: The aims of this study were to evaluate the prevalence of LHX4 mutations in patients with hypopituitarism, to define the associated phenotypes, and to characterize the functional impact of the identified variants and the respective role of the 2 LIM domains of LHX4., Design and Patients: We screened 417 unrelated patients with isolated growth hormone deficiency or combined pituitary hormone deficiency associated with ectopic posterior pituitary and/or sella turcica anomalies for LHX4 mutations (Sanger sequencing). In vitro studies were performed to assess the functional consequences of the identified variants., Results: We identified 7 heterozygous variations, including p.(Tyr131*), p.(Arg48Thrfs*104), c.606+1G>T, p.Arg65Val, p.Thr163Pro, p.Arg221Gln, and p.Arg235Gln), that were associated with variable expressivity; 5 of the 7 were also associated with incomplete penetrance. The p.(Tyr131*), p.(Arg48Thrfs*104), p.Ala65Val, p.Thr163Pro, and p.Arg221Gln LHX4 variants are unable to transactivate the POU1F1 and GH promoters. As suggested by transactivation, subcellular localization, and protein-protein interaction studies, p.Arg235Gln is probably a rare polymorphism. Coimmunoprecipitation studies identified LHX3 as a potential protein partner of LHX4. As revealed by functional studies of LIM-defective recombinant LHX4 proteins, the LIM1 and LIM2 domains are not redundant., Conclusion: This study, performed in the largest cohort of patients screened so far for LHX4 mutations, describes 6 disease-causing mutations that are responsible for congenital hypopituitarism. LHX4 mutations were found to be associated with variable expressivity, and most of them with incomplete penetrance; their contribution to pituitary deficits that are associated with an ectopic posterior pituitary and/or a sella turcica defect is ∼1.4% in the 417 probands tested., (Copyright © 2017 by the Endocrine Society)

Background: The incidence of childhood type 1 diabetes (T1D) incidence is rising in many countries, supposedly because of changing environmental factors, which are yet largely unknown. The purpose of the study was to unravel environmental markers associated with T1D., Methods: Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends of the patients. Parents were asked to fill a 845-item questionnaire investigating the child's environment before diagnosis. The analysis took into account the matching between cases and controls. A second analysis used propensity score methods., Results: We found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnut cocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a pet by old age., Conclusions: The found statistical association of new environmental markers with T1D calls for replication in other cohorts and investigation of new environmental areas., Trial Registration: Clinical-Trial.gov NCT02212522 . Registered August 6, 2014.

Study Design: Clinical measurement., Purpose: The test-retest reliability of maximal grip strength measurements (MGSM) is examined in subjects for 12 weeks post-stroke together with maximal grip strength recovery and the maximal-grip and upper-extremity strength measurements' relationship with capacity and performance test scores., Methods: A Jamar dynamometer and the Motricity Index (MI) were used for strength measurements. The Chedoke Arm and Hand Activity Inventory and ABILHAND questionnaire for evaluating capacities and performances., Results: MGSM were reliable (Intraclass Correlation Coefficients = 0.97-0.99, Minimal Detectable Differences = 2.73-4.68 kg). Among the 34 participants, 47% did not have a measurable grip strength one week post-stroke but 50% of these recovered some strength within the first eight weeks. The MGSM and MI scores were correlated with scores of tests of capacity and performance (Spearman's Rank Correlation Coefficients = 0.69-0.94)., Conclusions: MGSM are reliable in the first weeks after a stroke., Level of Evidence: N/A., (Copyright © 2015 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.)

Unlabelled: The Developmental Coordination Disorder Questionnaire (DCDQ'07) is a Canadian-English instrument recommended for screening children aged 5 to 15 years who are at risk for developmental coordination disorder. While a Canadian-French version of the DCDQ'07 presently exists, a European-French version does not., Aims: To produce a cross-cultural adaptation of the DCDQ'07 for use in areas of Europe where French is spoken and to test its cultural relevance in French-speaking Switzerland., Methods: Cross-cultural adaptation was done using established guidelines. Cultural relevance was analyzed with cognitive interviews of thirteen parents of children aged 5.0 to 14.6 years (mean age: 8.5 years, SD = 3.4), using think-aloud and probing techniques., Results: Cultural and linguistic differences were noted between the European-French, the Canadian-French, and the original versions of the DCDQ'07. Despite correct translation and expert committee review, cognitive interviews revealed that certain items of the European-French version were unclear or misinterpreted and further modifications were needed., Conclusions: After rewording items as a result of the outcomes of the cognitive interview, the European-French version of the DCDQ'07 is culturally appropriate for use in French-speaking Switzerland. Further studies are necessary to determine its psychometric properties.

The aim of the study was to evaluate, after the first year of a national information campaign, the effect on the frequency and severity of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) in children and adolescents in France. The following data were collected during a 2-year period in people younger than 15 years of age at diagnosis of T1D, in 146 pediatric centers: age, sex, duration of symptoms, patient's previous care, clinical and biological signs, and family history of T1D. DKA was defined as pH<7.30 or bicarbonate<15mmol/L, severe DKA as pH<7.10 or bicarbonate <5mmol/L. During the 2nd year, an information campaign targeting health professionals and families was launched with the objective of reducing the time to diagnosis. Data were compared between the year before the campaign (year 0) and the first year of the campaign (year 1). The number of new cases of T1D was 1299 for year 0 and 1247 for year 1. Between year 0 and year 1, the rate of DKA decreased from 43.9% to 40.5% (P=0.08), exclusively due to the decrease of severe DKA from 14.8 to 11.4% (P=0.01). In the 0- to 5-year-old and 5- to 10-year-old age groups, the relative decrease in the rate of DKA was 13% and 15%, and 23% and 41% for severe DKA, respectively. In patients referred to the hospital by a pediatrician or who came at the family's initiative, the decrease was 34% and 7%, and 39% and 32% for severe DKA, respectively. No change was observed in the 10- to 15-year-old group or in those children who were referred by a general practitioner. In multivariate analyses, a higher DKA rate was associated with the young age of the child (<5 years), being hospitalized at the parents' initiative rather than being referred by a doctor, and the absence of a family history of T1D. A higher rate of severe DKA was associated with these last two factors but not with the child's age. The frequency of DKA at diagnosis of type 1 diabetes remains high in children and adolescents, but the first year of an information campaign decreased it. The results have also helped better define the strategy and targets of the continuing prevention campaign, to more efficiently reduce the morbidity and mortality of T1D at diagnosis in children and adolescents in France., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objectives: This study aimed to evaluate the frequency of diabetic ketoacidosis (DKA) and its associated factors at the diagnosis of type 1 diabetes (T1D) in French children and adolescents prior to launching a public-health campaign of information to prevent DKA., Patients and Methods: Over a 1-year period, 1299 youngsters (aged < 15 years) were diagnosed with T1D at 146 paediatric centres in all regions of France. Age, gender, duration of symptoms, patient's pathway to diagnosis, clinical and biological signs, and family history of T1D were collected for each newly diagnosed patient. DKA was defined as pH < 7.30 or bicarbonate < 15 mmol/L, and severe DKA as pH < 7.10 or bicarbonate < 5 mmol/L., Results: At the time of diagnosis, 26% of the children were aged 0-5 years, 34% were 5-10 years and 40% were 10-15 years. The overall prevalence of DKA was 43.9% (0-5 years: 54.2%; 5-10 years: 43.4%; and 10-15 years: 37.1%) and 14.8% for severe DKA (0-5 years: 16.6%; 5-10 years: 14.4%; and 10-15 years: 13.9%; < 2 years: 25.3%). Severe DKA was more frequent when the child was hospitalized at the family's behest (26.6%) than when referred by a general practitioner (7.6%) or paediatrician (5.1%; 30.6%, 53.7% and 9.2%, respectively, by patients' age group). The frequency of DKA decreased to 20.1% (severe DKA: 4.4%) in families with a history of T1D. Multivariate analysis showed that age, pathway to diagnosis, duration of polyuria/polydipsia (< 1 week) and family history of T1D were associated with the presence of DKA, while pathway to diagnosis and family history of T1D were associated with severe DKA., Conclusion: DKA at the time of T1D diagnosis in children and adolescents is frequent and often severe. Patients' age, pathway to hospitalization and family history of diabetes were the main factors associated with DKA. These data suggest that a public-health campaign to prevent DKA at diagnosis can help reduce the frequency of DKA and also provide baseline data for evaluating the efficacy of such a campaign., (Copyright © 2014. Published by Elsevier Masson SAS.)

The development of personalised training programmes is crucial in the management of obesity. We evaluated the ability of 2 heart rate variability analyses to determine ventilatory thresholds (VT) in obese adolescents. 20 adolescents (mean age 14.3±1.6 years and body mass index z-score 4.2±0.1) performed an incremental test to exhaustion before and after a 9-month multidisciplinary management programme. The first (VT1) and second (VT2) ventilatory thresholds were identified by the reference method (gas exchanges). We recorded RR intervals to estimate VT1 and VT2 from heart rate variability using time-domain analysis and time-varying spectral-domain analysis. The coefficient correlations between thresholds were higher with spectral-domain analysis compared to time-domain analysis: Heart rate at VT1: r=0.91 vs. =0.66 and VT2: r=0.91 vs. =0.66; power at VT1: r=0.91 vs. =0.74 and VT2: r=0.93 vs. =0.78; spectral-domain vs. time-domain analysis respectively). No systematic bias in heart rate at VT1 and VT2 with standard deviations <6 bpm were found, confirming that spectral-domain analysis could replace the reference method for the detection of ventilatory thresholds. Furthermore, this technique is sensitive to rehabilitation and re-training, which underlines its utility in clinical practice. This inexpensive and non-invasive tool is promising for prescribing physical activity programs in obese adolescents., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Neonatal diabetes mellitus is a rare genetic form of pancreatic β-cell dysfunction. We compared phenotypic features and clinical outcomes according to genetic subtypes in a cohort of patients diagnosed with neonatal diabetes mellitus before age 1 year, without β-cell autoimmunity and with normal pancreas morphology., Methods: We prospectively investigated patients from 20 countries referred to the French Neonatal Diabetes Mellitus Study Group from 1995 to 2010. Patients with hyperglycaemia requiring treatment with insulin before age 1 year were eligible, provided that they had normal pancreatic morphology as assessed by ultrasonography and negative tests for β-cell autoimmunity. We assessed changes in the 6q24 locus, KATP-channel subunit genes (ABCC8 and KCNJ11), and preproinsulin gene (INS) and investigated associations between genotype and phenotype, with special attention to extra-pancreatic abnormalities., Findings: We tested 174 index patients, of whom 47 (27%) had no detectable genetic defect. Of the remaining 127 index patients, 40 (31%) had 6q24 abnormalities, 43 (34%) had mutations in KCNJ11, 31 (24%) had mutations in ABCC8, and 13 (10%) had mutations in INS. We reported developmental delay with or without epilepsy in 13 index patients (18% of participants with mutations in genes encoding KATP channel subunits). In-depth neuropsychomotor investigations were done at median age 7 years (IQR 1-15) in 27 index patients with mutations in KATP channel subunit genes who did not have developmental delay or epilepsy. Developmental coordination disorder (particularly visual-spatial dyspraxia) or attention deficits were recorded in all index patients who had this testing. Compared with index patients who had mutations in KATP channel subunit genes, those with 6q24 abnormalities had specific features: developmental defects involving the heart, kidneys, or urinary tract (8/36 [22%] vs 2/71 [3%]; p=0·002), intrauterine growth restriction (34/37 [92%] vs 34/70 [48%]; p<0·0001), and early diagnosis (median age 5·0 days, IQR 1·0-14·5 vs 45·5 days, IQR 27·2-95·0; p<0·0001). Remission of neonatal diabetes mellitus occurred in 89 (51%) index patients at a median age of 17 weeks (IQR 9·5-39·0; median follow-up 4·7 years, IQR 1·5-12·8). Recurrence was common, with no difference between the groups who had 6q24 abnormalities versus mutations in KATP channel subunit genes (82% vs 86%; p=0·36)., Interpretation: Neonatal diabetes mellitus is often associated with neuropsychological dysfunction and developmental defects that are specific to the underlying genetic abnormality. A multidisciplinary assessment is therefore essential when patients are diagnosed. Features of neuropsychological dysfunction and developmental defects should be tested for in adults with a history of neonatal diabetes mellitus., Funding: Agence Nationale de la Recherche-Maladies Rares Research Program Grant, the Transnational European Research Grant on Rare Diseases, the Société Francophone du Diabète-Association Française du Diabète, the Association Française du Diabète, Aide aux Jeunes Diabétiques, a CIFRE grant from the French Government, HRA-Pharma, the French Ministry of Education and Research, and the Société Française de Pédiatrie., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Unlabelled: BACKGROUNDAIM: In growth disorders, ensuring long-term growth hormone therapy (GHT) remains a challenge that might compromise the clinical outcome. Consequently, strategies aiming at alleviating the burden of daily injection might improve the treatment benefit. The study reported here was performed to assess the ease of use of Norditropin NordiFlex(®) (Novo Nordisk, Princeton, NJ, USA) compared with that of the devices previously used in children treated with GHT with recombinant somatropin., Methods: This Phase IV prospective, multicenter, open-label study was conducted in France. All patients received Norditropin NordiFlex for 6 weeks. Oral questionnaires were administered by the physician to the patients and/or the parents at inclusion and at the final visit., Results: This study included 103 patients aged between 6 and 17 years. The patients assessed Norditropin NordiFlex as significantly easier to use than their previous device (median value = 7.5, P < 0.001). Almost three-quarters of patients (64.4%) preferred Norditropin NordiFlex to their previous device. Among physicians and nurses, 73% assessed Norditropin NordiFlex training as "very easy" and 26% as "easy." Norditropin NordiFlex improved patient autonomy, with 41% of patients able to self-inject the treatment., Conclusion: This study has shown that Norditropin NordiFlex is reliable, safe, and easy to use and most study patients preferred it to their previous device. These characteristics may improve the adherence to GHT.

The causes of Reye-like syndrome are not completely understood. Dihydrolipoamide dehydrogenase (DLD or E3) deficiency is a rare metabolic disorder causing neurological or liver impairment. Specific changes in the levels of urinary and plasma metabolites are the hallmark of the classical form of the disease. Here, we report a consanguineous family of Algerian origin with DLD deficiency presenting without suggestive clinical laboratory and anatomopathological findings. Two children died at birth from hepatic failure and three currently adult siblings had recurrent episodes of hepatic cytolysis associated with liver failure or Reye-like syndrome from infancy. Biochemical investigation (lactate, pyruvate, aminoacids in plasma, organic acids in urine) was normal. Histologic examination of liver and muscle showed mild lipid inclusions that were only visible by electron microscopy. The diagnosis of DLD deficiency was possible only after genome-wide linkage analysis, confirmed by a homozygous mutation (p.G229C) in the DLD gene, previously reported in patients with the same geographic origin. DLD and pyruvate dehydrogenase activities were respectively reduced to 25% and 70% in skin fibroblasts of patients and were unresponsive to riboflavin supplementation. In conclusion, this observation clearly supports the view that DLD deficiency should be considered in patients with Reye-like syndrome or liver failure even in the absence of suggestive biochemical findings, with the p.G229C mutation screening as a valuable test in the Arab patients because of its high frequency. It also highlights the usefulness of genome-wide linkage analysis for decisive diagnosis advance in inherited metabolic disorders., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Patients with inherited factor VII (FVII) deficiency display different clinical phenotypes requiring ad hoc management. This study evaluated treatments for spontaneous and traumatic bleeding using data from the Seven Treatment Evaluation Registry (STER). One-hundred one bleeds were analysed in 75 patients (41 females; FVII coagulant activity <1-20%). Bleeds were grouped as haemarthroses (n=30), muscle/subcutaneous haematomas (n=16), epistaxis (n=12), gum bleeding (n=13), menorrhagia (n=16), central nervous system (CNS; n=9), gastrointestinal (GI; n=2) and other (n=3). Of 93 evaluable episodes, 76 were treated with recombinant, activated FVII (rFVIIa), eight with fresh frozen plasma (FFP), seven with plasma-derived FVII (pdFVII) and two with prothrombin-complex concentrates. One-day replacement therapy resulted in very favourable outcomes in haemarthroses, and was successful in muscle/subcutaneous haematomas, epistaxis and gum bleeding. For menorrhagia, single- or multiple-dose schedules led to favourable outcomes. No thrombosis occurred; two inhibitors were detected in two repeatedly treated patients (one post-rFVIIa, one post-pdFVII). In FVII deficiency, most bleeds were successfully treated with single 'intermediate' doses (median 60 µg/kg) of rFVIIa. For the most severe bleeds (CNS, GI) short- or long-term prophylaxis may be optimal.

Background: In humans, pituitary hormone deficiency may be part of a syndrome including extra-pituitary defects like ocular abnormalities. Very few genes have been linked to this particular phenotype. In the mouse, Lhx2, which encodes a member of the LIM (Lin-11, Isl-1, and Mec-3) class of homeodomain proteins, was shown to be expressed during early development in the posterior pituitary, eye, and liver, and its expression persists in adulthood in the central nervous system Lhx2(-/-) mice display absence of posterior pituitary and intermediate lobes, malformation of the anterior lobe, anophthalmia, and they die from anemia., Methods: We tested the implication of the LHX2 gene in patients presenting pituitary hormone deficiency associated with ectopic or nonvisible posterior pituitary and developmental ocular defects. A cohort of 59 patients, including two familial cases, was studied. Direct sequencing of the LHX2 coding sequence and intron/exon boundaries was performed. LHX2 transcriptional activity on several pituitary promoters (AGSU, PRL, POU1F1, and TSHB) was tested in vitro., Results: Six heterozygous sequence variations were identified, among which two are novel missense changes (p.Ala203Thr and p.Val333Met). In vitro, LHX2 activates transcription of TSHB, PRL, and POU1F1 promoters in the HEK293 cell line. A synergistic action of POU1F1 and LHX2 was also shown on these promoters. The two missense variations were tested and no significant difference was observed, leading to the conclusion that they are not deleterious., Conclusions: These results suggest that if LHX2 is involved in pituitary hormone deficiency associated with posterior pituitary and ocular defects, it would be a rare cause of this disease condition.

Background: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes., Methods: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels., Results: The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences., Conclusions: Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period. (Funded by Diamyd Medical and the Swedish Child Diabetes Foundation; ClinicalTrials.gov number, NCT00723411.).

Introduction: autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator gene (AIRE). We report the case of a young girl with APECED., Case Report: an 18 year-old girl born to consanguineous parents consulted for diffuse alopecia. Dermatological examination showed nail and dental enamel dystrophy and angular cheilitis. She had a history of mineralocorticoid deficiency (Addison's disease), hypoparathyroidism, hypogonadism and Biermer's disease, and she had also had chronic mucocutaneous candidiasis since childhood. She was presenting APECED with autoimmune endocrine failure, chronic mucocutaneous candidiasis and abnormalities of ectoderm-derived tissue. Analysis of mutation in the AIRE gene showed the c.769C>T homozygous mutation in exon 6., Discussion: APECED, a rare autosomal recessive disorder, is a potentially life-threatening autoimmune disease. Chronic mucocutaneous candidiasis is a common and early feature in children. Dermatologists are likely to be the first physicians to diagnose this syndrome., (2010. Published by Elsevier Masson SAS.)

Diamond-Blackfan anemia (DBA) is a rare disorder characterized by congenital pure red cell aplasia. Mutations in ribosomal protein S19 (RPS19) have been identified in 25% of DBA patients. More recently, mutations in other ribosomal protein genes, namely RPS7, RPS15, RPS24, RPS17, RPS27A, RPL35a, RPL36, RPL11, and RPL5, have also been found in patients with DBA. Approximately 30-40% of affected patients have various associated physical anomalies, mostly craniofacial and at the extremities, but also cardiac or urogenital malformations. Anomalies of the urogenital tract in DBA patients comprise changes in the kidney (dysplasia, agenesis, duplication, horseshoe kidney) and genitalia (hypospadias). To date, disorders of sex development (DSD) have only been described once in association with DBA. We report here four DBA patients who exhibited DSD.

This report describes two unrelated boys presenting with short stature, femoral metaphyseal abnormalities, platyspondyly, and retinitis pigmentosa. Patients share similar findings with cases described by Ehara et al. [Ehara et al. (1997); Eur J Pediatr 156:627-630] described as axial spondylometaphyseal dysplasia. The presence of consanguinity in one of our patients further supports an autosomal recessive mode of inheritance of what, we believe, constitutes a separate and distinct entity., ((c) 2010 Wiley-Liss, Inc.)

Context: Nonimmune fetal goitrous hypothyroidism is a rare condition that can induce obstetrical and/or neonatal complications and neurodevelopmental impairments such as those still seen in some patients with congenital hypothyroidism. Prenatal treatment to prevent these adverse outcomes is appealing, but experience is limited and the risk to benefit ratio controversial., Objective: The objective of the study was to evaluate the feasibility, safety, and effectiveness of intrauterine l-thyroxine treatment in a large cohort with nonimmune fetal goitrous hypothyroidism., Design: This was a retrospective study of 12 prenatally treated fetuses diagnosed between 1991 and 2005 in France., Methods: During pregnancy, goiter size and thyroid hormone levels were compared before and after prenatal treatment. At birth, clinical, laboratory, and ultrasound data were evaluated., Results: Prenatal treatment varied widely in terms of l-thyroxine dosage (200-800 microg/injection), number of injections (one to six), and frequency (every 1-4 wk). No adverse events were recorded. During pregnancy, thyroid size decreased in eight of nine cases and amniotic-fluid TSH levels decreased in the six investigated cases, returning to normal in four. However, at birth, all babies had hypothyroidism, indicating that intraamniotic TSH levels did not reliably reflect fetal thyroid function., Conclusion: Our data confirm the feasibility and safety of intraamniotic l-thyroxine treatment for nonimmune fetal goitrous hypothyroidism. Although goiter size reduction is usually obtained, thyroid hormone status remains deficient at birth. Amniocentesis seems inadequate for monitoring fetal thyroid function. Further studies are needed to determine the optimal management of this disorder.

Context: Russell-Silver syndrome (RSS), characterized by intrauterine and postnatal growth retardation, dysmorphic features, and frequent body asymmetry, spares cranial growth. Maternal uniparental disomy for chromosome 7 (mUPD7) is found in 5-10% of cases. We identified loss of methylation (LOM) of 11p15 Imprinting Center Region 1 (ICR1) domain (including IGF-II) as a mechanism leading to RSS., Objective: The aim was to screen for 11p15 epimutation and mUPD7 in RSS and non-RSS small-for-gestational-age (SGA) patients and identify epigenetic-phenotypic correlations. STUDIED POPULATION AND METHODS: A total of 127 SGA patients were analyzed. Clinical diagnosis of RSS was established when the criterion of being SGA was associated with at least three of five criteria: postnatal growth retardation, relative macrocephaly, prominent forehead, body asymmetry, and feeding difficulties. Serum IGF-II was evaluated for 82 patients., Results: Of the 127 SGA patients, 58 were diagnosed with RSS; 37 of these (63.8%) displayed partial LOM of the 11p15 ICR1 domain, and three (5.2%) had mUPD7. No molecular abnormalities were found in the non-RSS SGA group (n = 69). Birth weight, birth length, and postnatal body mass index (BMI) were lower in the abnormal 11p15 RSS group (ab-ICR1-RSS) than in the normal 11p15 RSS group [-3.4 vs.-2.6 SD score (SDS), -4.4 vs.-3.4 SDS, and -2.5 vs.-1.6 SDS, respectively; P < 0.05]. Among RSS patients, prominent forehead, relative macrocephaly, body asymmetry, and low BMI were significantly associated with ICR1 LOM. All ab-ICR1-RSS patients had at least four of five criteria of the scoring system. Postnatal IGF-II levels were within normal values., Conclusion: The 11p15 ICR1 epimutation is a major, specific cause of RSS exhibiting failure to thrive. We propose a clinical scoring system (including a BMI < -2 SDS), highly predictive of 11p15 ICR1 LOM, for the diagnosis of RSS.

Extranodal thyroid lymphomatous involvement is rare in childhood. We report here 2 children, 1 with vertical transmission-acquired human immunodeficiency virus (HIV), presenting with lymphomatous infiltration of the thyroid gland at diagnosis. One child had infra-clinical endocrine impairment and both responded well to chemotherapy. Although the cases are too scarce to be affirmative, thyroid gland involvement doesn't seem to alter the good prognosis of childhood Burkitt's lymphoma. The third child's cancer in frequency is Non-Hodgkin Lymphomas. Presenting as the initial AIDS event in 1 patient, this case report also highlights the need to systematically propose antiretroviral therapy in vertically HIV infected children.

Context: CHARGE (coloboma, heart defect, choanal atresia, retarded growth and development, genital hypoplasia, ear abnormalities, and/or hearing loss defect) syndrome consists of a combination of congenital malformations including genital hypoplasia and retarded growth., Objective: The objective of the study was to study gonadotropic axis function and growth parameters in CHARGE syndrome., Design: This was a retrospective study., Patients: The study included 32 children with CHARGE syndrome., Results: Nineteen of 20 affected boys had micropenis and/or cryptorchidism, consistent with hypogonadotropic hypogonadism during fetal life. None of the boys was of pubertal age. Seven of nine boys tested before the age of 5 months during the neonatal peak period had extremely low testosterone levels. LH response to GnRH stimulation was variable during the first year of life and not correlated with existing clinical abnormalities. None of the girls over the age of 12 yr (n = 7) had begun puberty spontaneously, and a lack of response to GnRH stimulation was documented in five of them. Olfactory evaluation (n = 10) and magnetic resonance imaging (n = 18) of the forebrain revealed defective sense of smell and abnormal olfactory bulbs in all cases. Cardiorespiratory and nutritional problems were corrected, but the mean height of the 25 children who had reached 5 yr of age was -2 +/- 0.2 sd score. Height was not correlated with birth length or body mass index. GH deficiency was diagnosed in only three children., Conclusion: These findings suggest that CHARGE syndrome includes the main features of Kallmann syndrome, which is defined by hypogonadotropic hypogonadism combined with a defective sense of smell and abnormal olfactory bulb development. This forebrain abnormality, if confirmed in a larger group of patients, could serve as a major new criterion for the diagnosis of CHARGE syndrome.

Silver-Russell syndrome (SRS, OMIM 180860) is a congenital disorder characterized by severe intrauterine and postnatal growth retardation, dysmorphic facial features and body asymmetry. SRS is genetically heterogenous with maternal uniparental disomy with respect to chromosome 7 occurring in approximately 10% of affected individuals. Given the crucial role of the 11p15 imprinted region in the control of fetal growth, we hypothesized that dysregulation of genes at 11p15 might be involved in syndromic intrauterine growth retardation. We identified an epimutation (demethylation) in the telomeric imprinting center region ICR1 of the 11p15 region in several individuals with clinically typical SRS. This epigenetic defect is associated with, and probably responsible for, relaxation of imprinting and biallelic expression of H19 and downregulation of IGF2. These findings provide new insight into the pathogenesis of SRS and strongly suggest that the 11p15 imprinted region, in addition to those of 7p11.2-p13 and 7q31-qter, is involved in SRS.

Objective: It has been suggested that the measurement of strength is inappropriate in patients with stroke, in large part because of the presence of abnormal synergy patterns. The aim of the present study was to characterize force production during multi-joint maximal exertion involving different combinations of activation between shoulder and elbow flexors and extensors., Design: Cross-sectional study., Setting: Rehabilitation centre., Subjects: A convenience sample of 16 chronic hemiparetic stroke subjects., Main Outcome Measures: Maximal torques in flexion and extension at the shoulder and the elbow were measured using static dynamometers (single-joint condition). In addition, the maximal forces produced at the wrist were measured in four directions in the sagittal plane requiring different torque combinations between shoulder and elbow flexors and extensors (multi-joint condition)., Results: No difference was found across directions for the ratios of maximal forces (paretic/nonparetic) in the multi-joint condition (p = 0.227; mean ratios (+/- SD) for each direction ranging from 0.59+/-0.23 to 0.68+/-0.27), suggesting that the ability to produce force did not change as a function of the required torque combination. In addition, relative torques (% of the maximal torque in the single-joint condition) exerted during the multi-joint exertions were similar on the paretic and the nonparetic side., Conclusions: These results do not support the assumption that force production is limited by abnormal synergy patterns between flexors and extensors at the shoulder and the elbow in hemiparetic patients.

Stroke patients often exhibit large imbalances in strength between the two upper limbs (ULs) and between the different muscle groups of the paretic UL. The aim of the study was to compare the ability of hemiparetic and normal subjects to produce symmetrical forces with both ULs and to determine whether the differences between force vectors can be predicted by a model accounting for the weakness of the different muscle groups or from clinical characteristics. Sixteen hemiparetic and 16 control subjects were assessed using static dynamometers in which both ULs were fixed. They were asked to produce symmetrical sub-maximal forces (in terms of direction and magnitude) with both ULs in four directions in the sagittal plane, which covers all possible combinations of flexion and extension at the shoulder and the elbow. Fifteen trials were performed, and the subjects were asked to gradually increase the forces produced from one trial to another. In addition, the maximal voluntary force (MVF) was measured unilaterally on both sides under two conditions: single-joint MVF (isolated flexion or extension at the elbow or the shoulder) and multi-joint MVF (same directions as the bilateral task). During the bilateral task, the stroke subjects generally showed larger errors between limbs than the control subjects, although they were able to produce sufficient force in the required directions during multi-joint MVF. The difference between groups was statistically significant in the four target directions for the errors in the magnitude, and in two target directions for the errors in direction (p<0.01). Differences predicted by a model based on the relative single-joint MVFs show a moderate association with errors observed for the magnitude (p=0.001-0.11, R2=0.17-0.54), but not for the direction of forces (p>0.1, R2<0.16). Several clinical features were examined as potential predictors using stepwise multiple regressions. The mean multi-joint MVF and proprioceptive impairments were the best predictors of mean errors in the magnitude of force (p<0.001, R2=0.82) whereas the mean angular errors were best explained by proprioceptive impairments (p=0.01, R2=0.38). Inaccurate internal representations of the paretic UL might explain why asymmetries were observed even though motor capacities were sufficient to perform successfully.

It has been shown that, in a bilateral force-matching task, subjects presenting weakness in one limb produce a lower force in the weakened limb even though they subjectively perceive that they are exerting the same force. The aim of this study was to verify whether subjects with hemiparesis produced asymmetrical forces during a bilateral submaximal grip task and whether this asymmetry is related to weakness of the paretic limb. Fifteen subjects with hemiparesis and 15 healthy subjects were recruited. First, the maximal voluntary force was measured for each hand. Then, subjects were asked to exert equal forces with both hands simultaneously at three submaximal force levels using two dynamometers. In the bilateral task, the force ratios (paretic/nonparetic or nondominant/dominant) differed between groups. Severely weak hemiparetic subjects produced lower force ratios than mildly weak hemiparetic subjects and healthy subjects (P < 0.000), whereas there was no difference between the force ratios produced by mildly weak hemiparetic subjects and those produced by healthy subjects. In subjects with hemiparesis, the force ratios in the bilateral task were related to the ratios of maximal voluntary forces (R2 = 0.39-0.66, P < or = 0.013) and the presence of somatosensory impairment did not affect these relationships. These results suggest that the strategy used is to compare the intensity of the motor commands on both sides and then perform the force-matching task. The use of such a strategy by subjects who have had paresis for 1 year reflects a lack of adaptation to their weakness.

Objectives: To describe a large cohort of patients with transient neonatal diabetes mellitus (TNDM) and permanent neonatal diabetes mellitus (PNDM), and to investigate whether chromosome 6 analysis helps to distinguish TNDM from PNDM., Study Design: Patients with TNDM (n = 29) (insulin therapy for <3 years) and 21 with PNDM were identified through a nationwide study., Results: Although patients with PNDM were less likely to have had intrauterine growth restriction (36% vs 74% for TNDM, P <.006), were older at diagnosis (median: 27 vs 6 days, P <.01), and had higher initial insulin requirements (1.4 U/kg/day vs 0.6 U/kg/day, P <.006), no clinical features were reliable in distinguishing PNDM from TNDM on an individual case basis. Permanent insulin-dependent diabetes developed in 5 TNDM patients after 8 years of age, emphasizing the need for prolonged follow-up. Among the 19 TNDM patients tested, two had paternal isodisomy of chromosome 6, seven from 4 families had paternally-derived trisomy of the 6q region, and two had a methylation defect in the 6q24 region. No chromosome 6 anomalies were found in the 9 PNDM patients tested., Conclusion: When present, a chromosome 6 abnormality is strongly in favor of the "transient" form of the disease.

Androgen insensitivity syndromes (AIS) result from the incapacity for T and dihydrotestosterone to virilize male embryos and is mainly attributable to molecular defects of the AR gene. In normal males, T and LH rise during the first few months of life, and this physiological surge is commonly used to evaluate the gonadotropic axis at this age. This neonatal surge has not been evaluated in detail in newborns with AIS. We sequentially measured plasma T, LH, and FSH during the first 3 months of life in 15 neonates with AIS and AR mutation. A GnRH and an human CG stimulation test were also performed. Patients were divided in 2 groups with complete (n = 10) or partial (n = 5) AIS (CAIS or PAIS), based on the clinical phenotype. In patients with PAIS, T levels were in the high-normal range at d 30 (18.4 +/- 6.9 nM) and d 60 (12.8 +/- 3.8 nM). In contrast, plasma T values were below the normal range in 9 of 10 patients with CAIS at d 30 (1 +/- 0.3 nM) and d 60 (1.4 +/- 0.7 nM, both P < 0.004 vs. PAIS). Plasma LH values were low in CAIS at d 30 (0.7 +/- 0.1U/liter) and increased normally in PAIS (8.7 +/- 2.5 U/liter, P = 0.004). We conclude that the postnatal T and LH surge occurs expectedly in neonates with PAIS but is absent in those with CAIS and that the postnatal T rise requires the receptivity of the hypothalamo-pituitary axis to T.

Objective: To characterize postural stabilization during a progressive unilateral isometric abduction of the upper limb in a seated position in healthy subjects and subjects with hemiparesis., Design: Convenience sample., Setting: University secondary care rehabilitation center., Patients: Twelve patients with hemiparesis and 12 subjects without neurologic disorder., Interventions: Subjects were seated on a forceplate, with forearms fixed in cuffs mounted on a force transducer. Two trials per side of isometric abduction of arm were conducted. The orthogonal force and torque exerted was measured for each arm., Main Outcome Measures: Forces at the upper limbs and at the seat, global motor performance, spasticity of upper limb, grip force, and dexterity., Results: Results of analyses of variance showed differences in the magnitude of the contralateral limb forces generated by subjects with hemiparesis and healthy subjects (p <.05). Normalized contralateral forces in the nonparetic upper limb associated with paretic isometric efforts were higher than those associated with nonparetic efforts and higher than those associated with efforts in healthy subjects., Conclusion: These results suggest that postural stabilization during isometric efforts is impaired in subjects with hemiparesis.

Fetal male sexual differentiation is driven by two testicular hormones: testosterone (synthesized by interstitial Leydig cells) and antimüllerian hormone (AMH; produced by Sertoli cells present in the seminiferous tubules). Intersex states result either from gonadal dysgenesis, in which both Leydig and Sertoli cell populations are affected, or from impaired secretion or action of either testosterone or AMH. Until now, only Leydig cell function has been assessed in children with ambiguous genitalia, by means of testosterone assay. To determine whether serum AMH would help in the diagnosis of intersex conditions, we assayed serum AMH levels in 107 patients with ambiguous genitalia of various etiologies. In XY patients, AMH was low when the intersex condition was caused by abnormal testicular determination (including pure and partial gonadal dysgenesis) but was normal or elevated in patients with impaired testosterone secretion, whereas serum testosterone was low in both groups. AMH was also elevated during the first year of life and at puberty in intersex states caused by androgen insensitivity. In 46,XX patients with a normal male phenotype or ambiguous genitalia, in whom the diagnosis of female pseudohermaphroditism had been excluded, serum AMH levels higher than 75 pmol/L were indicative of the presence of testicular tissue and correlated with the mass of functional testicular parenchyma. In conclusion, serum AMH determination is a powerful tool to assess Sertoli cell function in children with intersex states, and it helps to distinguish between defects of male sexual differentiation caused by abnormal testicular determination and those resulting from isolated impairment of testosterone secretion or action.

Gametophytes ofOsmunda regalis were culturedin vitro to determine the optimal conditions for growth and development. Culture media with low ammonium concentration (Knop, Knudson or 1/4 Murashige and Skoog dilution) were the most effective for growth of this organism. Addition of sucrose and mannitol to the culture medium at the same osmoticum, inhibits or enhances, respectively, growth and development of the gametophytes, which show a strong autotrophyin vitro. In darkness, both two-dimensional growth and sexual organ formation took place. Gemmae formation is described for the first time in this species and this process does not occur without sucrose in the culture medium or in darkness.

Background: Treatment of hyperthyroidism in those neonates born to mothers with Grave's disease is difficult. Calcium ipodate, an agent for oral cholecystography, inhibits extra-thyroid conversion of T3 to T4 and diminishes thyroid secretion., Case Reports: Two neonates with clinical manifestations and biological findings of hyperthyroidism were given calcium ipodate orally, 400 mg every 3 days, from day 26 to 50 for the first patient and from day 9 to 18 for the second in association with a beta blocker. Clinical manifestations disappeared within 2 days and circulating levels of T3 and T4 were normalized within 2-5 days., Conclusions: This treatment was effective and well-tolerated in both patients and in three others previously reported; it should be confirmed in a larger number of patients and controlled by measuring levels of antibodies directed against thyrotropin-releasing hormone receptors in order to avoid relapse after cessation of treatment as seen in our second patient.

Objective: There have been few studies of GH dose responses in Turner's syndrome. We have therefore compared the growth effect of two doses of subcutaneous GH: 0.45 (D1) or 0.90 (D2) IU/kg/week., Design: Multicentre study with two parallel randomized groups treated with D1 or D2 dose for one year, then with D2 for the second and third years in both groups., Patients: Ninety-seven girls with Turner's syndrome aged from 4.8 to 16.5 years., Results: The first mean height velocity (HV) was significantly higher with D2. At one year the girls changed from D1 to D2 showed a further acceleration in HV. During second and third years HV remained above the mean for untreated Turner girls, in both groups. Mean cumulative height gains over the 3 years were 1.06 and 1.17 SDS/CA (Ranke's Turner standard) in groups G1 and G2 respectively. Bone maturation, over 36 months, was 33.7 (G1) and 31.9 (G2) months., Conclusion: These results suggest that, if a higher initial GH dose is associated with a greater net initial height gain, the duration of treatment might affect the long-term results. Intermittent treatment should be considered.

The first treatment trials on patients presenting with Turner syndrome were successful in accelerating growth velocity. It is therefore essential to know the final height of the patients who were treated in order to ascertain whether or not growth hormone treatment increases final height. We are reporting on a group of 117 patients with Turner syndrome whose growth hormone treatment was initiated in 1986. The mean growth hormone dose was 0.74 IU/kg/week for an average period of 4 years. At the start of treatment, the patients' chronological age was 129/12 years, height -3.8 +/- 1.0 standard deviation scores (SDS) and bone age 10.5 +/- 2.1 years. Mean final height was 147.7 +/- 5.6 cm, i.e. a gain of 1.5 SDS. We noted no significant difference due to the type of chromosomal abnormality, nor to oxandrolone or estrogen-associated treatment. A significant correlation was found between final height, mean parental height, the duration of the treatment, height SDS at the start of treatment and growth hormone peak during pharmacological stimulation tests. However, there was no correlation between growth hormone dosage, chronological age and bone age at the start of treatment. These results show that the growth hormone treatment improves the final heights of patients with Turner syndrome.