[The private pediatrician in the clinical care pathway for children affected by specific learning disorders in France]. / Le pédiatre libéral dans le parcours de soins des enfants présentant des troubles « dys ¼.

The clinical care pathway for children presenting specific learning disorders, including language, motor coordination, and attention disorders is based on different levels of assessment by the professionals involved. In France, a first step of organization was established in 2002 by founding of a network of structures devoted to clinical assessment of complex cases, research, and teaching for the professionals involved. Although this organization proved to contribute an essential service, the demand largely exceeded the availability of access. A three-level organization was therefore suggested in 2013 including a first-level devoted to clinical analysis of simple cases, together with the professionals involved in rehabilitation (i.e., speech therapists, occupational therapists, psychologists), a second-level in charge of analyzing complex situations, involving comorbidities and failure of first-level care, together with the already structured third level of assessment devoted to genetic disorders, severe situations, and association with neurological conditions. To plan the practical application of these different levels, we assessed the situation of ambulatory pediatricians working in private practice, because this network appeared to be the most available in France to play these roles. A survey was therefore conducted among the main representative association of pediatricians (Association française de pédiatrie ambulatoire), including 1565 members of the 2700 in activity in France, on their level of knowledge and clinical expertise, and the drawbacks encountered in their practice in this field. Of the 481 respondents (36%), 25% were not yet in 2016 self-confident in assuming a first-level role, while 56% were ready to participate in a first-level response and 18% in a second-level response. In the 5 upcoming years, the vast majority of pediatricians intended to progress in their involvement, which should provide all regions in France with a network of professionals able to respond to the specific needs of children (48% in the first-level and 43.5% in the second-level of expertise). Specific obstacles have already been encountered by professionals who wish to play a full role in this domain: insufficient funding for medical evaluations and lack of access to specialized evaluations. This survey emphasizes the need for obtaining access to both practical and theoretical professional development programs (77.5%), funding of clinical assessment time (76%), all of which need to be answered by the French health authorities. To date, very few nationwide programs of clinical care pathways in these fields have been developed, but examples are available in France on Alzheimer disease and elderly populations, providing a model for children affected by specific development and learning difficulties. Setting up a clinical care pathway by the French Ministry of Health (Haute Autorité de santé) assumes that the needs expressed by ambulatory pediatricians will be taken into account, including the design and implementation of Medical Education programs according to the level of expertise, together with the adequate funding of diagnosis, follow-up, and care pathway coordination time.

[Isolated primary nocturnal enuresis: international evidence based management. Consensus recommendations by French expert group]. / Enurésie nocturne primaire isolée: diagnostic et prise en charge. Recommandations par consensus formalisé d'experts.

OBJECTIVE: The causes and treatment of isolated primary nocturnal enuresis (PNE) are the subject of ongoing controversy. We are proposing consensus practical recommendations, based on a formalised analysis of the literature and validated by a large panel of experts. METHODOLOGY: A task force of six experts based its work on the guide for literature analysis and recommendations and recommendation grading of the French Haute Autorité de Santé (formalized consensus process methodological guidelines) to evaluate the level of scientific proof (grade of 1 to 4) and the strength of the recommendations (grade A, B, C) of the publications on PNE. As a result of this, 223 articles from 2003 on were identified, of which only 127 (57 %) have an evaluable level of proof. This evaluation was then reviewed by a 19-member rating group. Several recommendations, poorly defined by the literature, had to be proposed by a professional agreement resulting from a consultation between the members of the task force and those of the rating group. For its final validation, the document was submitted to a reading group of 21 members working in a wide range of specialist areas and practices but all involved in PNE. RESULTS: The definition of PNE is very specific: intermittent incontinence during sleep, from the age of 5, with no continuous period of continence longer than 6 months, with no other associated symptom, particularly during the day. Its diagnosis is clinical by the exclusion of all other urinary pathologies. Two factors must be identified during the consultation: nocturnal polyuria promoted by excessive fluid intake, inverse secretion of vasopressin, snoring and sleep apnoea. It is sensitive to desmopressin; small bladder capacity evaluated according to a voiding diary and the ICCS formula. It may be associated with diurnal hyperactivity of the detrusor (30 %). It is resistant to desmopressin. Problems associated with PNE are: abnormal arousal threshold, attention deficit hyperactivity disorder (ADHD) (10 %), low self-esteem. The psychological component is not very significant. CONCLUSION: PNE is not psychological in origin. The management of this condition includes: evaluating the intrafamilial tolerance and the child's motivation, evaluating the rate, the volume of urine and wet nights using a diurnal and nocturnal diary; education (sufficient fluid intake at the start of the day, decrease in hyperosmolar intake in the evening, regular and complete urination); specific treatments: desmopressin for polyuric forms (expected success rate of 60-70 %), alarms for forms involving small bladder capacity (expected success rate of 60-80 %); alternative treatments and/or treatments combined with the preceding ones, for refractory forms: oxybutinin, tricyclic antidepressants (risk). Results obtained with hypnosis, psychotherapy, acupuncture, homoeopathy or chiropractic are not currently validated (insufficient level of proof).

[Validation of a screening test of language and learning disorders for 6-year old children (ERTLA6)--a prospective study]. / Validité des epreuves du repérage des troubles du langage et des apprentissages de l'enfant de 6 ans (ERTLA6)--etude prospective.

Medical practitioners are, like the other health, education and childhood professionals, important actors of the language and learning disorders' screening. Six years old--the age at which children start the elementary school--is a key age for this screening. At the request of practitioners, a multidisciplinary staff had developed a screening tool: ERTLA6 (Epreuves de repérage des troubles du langage et des apprentissages de l'enfant de 6 ans). The objective was to validate the capacity of ERTLA6 to predict the school performance. A sample of 187 children was randomly constituted among the whole population of last year nursery school children in an area of France (the Académie de Nancy-Metz). Those children, aged from 5 to 6, were screened with ERTLA6 by the school practitioner during a medical visit (score from 0 [the best] to 18 [the worse]). The School outcomes (considered as judgment criteria) were assessed 2 or 3 years later, after two years of elementary school. 148 children had completed their follow-up (the others: 27 moving house, 6 absents the day of evaluation, 2 missing data). Mean age was 5; 10 years. With a threshold > or = 7, ERTLA6 sensibility and specificity were respectively 79% [63-94] and 87% [81-93]; the positive predictive value was 58% [42-74], the negative predictive value was 95% [90-99]. The percentage of well classified children was 84% [69-99]. To our knowledge, ERTLA6 is the first validated tool in France for screening language and learning disorders which can be used by practitioners for the prediction of school outcomes.

[Clinical data on the diagnosis of colic in infants. Survey in 2,773 infants aged 15-119 days. Groupment des pédiatres de la région de Lyon (GPRL), le Groupment lyonnais de recherche en pédiatrie ambulatoire (GLYRPA), l'association des pédiatres de la région stéphanoise (APRS) et la Formation pédiatrique grenobloise (FPG)]. / Eléments cliniques du diagnostic de coliques du nourrisson. Enquête chez 2773 nourrissons âgés de 15 à 119 jours. Groupement des pédiatres de la région de Lyon (GPRL), le Groupement lyonnais de recherche en pédiatrie ambulatoire (GLYRPA), l'association des pédiatres de la région stéphanoise (APRS) et la Formation pédiatrique grenobloise (FPG).

BACKGROUND: Crying is called "Infantile colic" when such cries are numerous, paroxystic, difficult to comfort, and without an obvious cause. METHODOLOGY: An information mailing on the study (named Encolie) and the associated methodology was distributed in April 1995 to 212 private practice pediatricians. They have included in the study all infants aged 15 to 119 days who were seen during consultation from June 12 to June 27. They filled out a two page, 32 item, epidemiological questionnaire. Question 31 asked; "following this consultation, would you call for an 'infantile colic' diagnosis for this child? Yes, no. if no, what is your diagnosis?" RESULTS: One hundred and sixty-nine private practice pediatricians out of 212 (79.7%) participated in the study, and have included 2,797 infants 2,773 infant files were analyzed. The 625 infants identified as "colic" (22.5% of all cases), differed from the 2,148 identified as "non-colic" by the following factors: average age (51.3 vs 61.3 days), birth weight (2,226 vs 3,307 g), being a first born (52.7 vs 45.1% of cases), and mother's anxiety (47.8 vs 29.1% of cases). Significant differences were observed concerning feeding behavior (slow or gluttonous feeding), digestive symptoms, and unexplained crying, always more frequent in the case of the infants identified as "colic". These infants received more drugs, and their parents were given more advice on diet and hygiene. The symptoms supporting the "infantile colic" diagnosis were derived using a statistical regression model. They included: frequent and/or unexplained crying at the time of the study, frequent and/or unexplained crying in the past, abdominal distention at the time of the clinical examination, and frequent gas emissions as indicated by parental questioning. Factors associated with this diagnosis were: young age of the child, drugs administered before the consultation, maternal anxiety, anomalies in feeding behavior, and to a lesser degree, low birth weight and mother or father atopy. CONCLUSION: Given the sample size and origin, and the rigor of both the study and the analysis, we believe that these data could be extrapolated to the usual pediatrician's patient population. This highlighting of differences between our two groups indicate the validity of this diagnosis.

[Neutropenia from oxacillin. 3 pediatric cases]. / Neutropénies sous oxacilline. 3 observations pédiatriques.

Neutropenia developed in 3 pediatrics patients during treatment with oxacillin. The time of onset ranged from 18 to 24 days after beginning treatment with dose of 150 mg/kg/24 h. Concomitant symptoms were fever and rashes. During treatment with oxacillin it is necessary to monitor blood cell count every week.

Biological and physical properties of a beta-endorphin analog containing only D-amino acids in the amphiphilic helical segment 13-31.

Our approach to the modeling of beta-endorphin has been based on the proposal that three basic structural units can be distinguished in the natural peptide hormone: a highly specific opiate recognition sequence at the N terminus (residues 1-5) connected via a hydrophilic link (residues 6-12) to a potential amphiphilic helix in the C-terminal residues 13-31. Our previous studies showed the validity of this approach and have demonstrated the importance of the amphiphilic helical structure in the C terminus of beta-endorphin. The present model, peptide 5, has been designed in order to evaluate further the requirements of the amphiphilic secondary structure as well as to determine the importance of this basic structural element as compared to more specific structural features which might occur in the C-terminal segment. For these reasons, peptide 5 retains the three structural units previously postulated for beta-endorphin; the major difference with regard to previous models is that the whole C-terminal segment, residues 13-31, has been built using only D-amino acids. In aqueous buffered solutions as well as in 2,2,2-trifluoroethanol-containing solutions, the CD spectra of peptide 5 show the presence of a considerable amount of left-handed helical structure. Enzymatic degradation studies employing rat brain homogenate indicate that peptide 5 is stable in this milieu. In delta- and mu-opiate receptor-binding assays, peptide 5 shows a slightly higher affinity than beta-endorphin for both receptors while retaining the same delta/mu selectivity. In opiate assays on the guinea pig ileum, the potency of peptide 5 is twice that of beta-endorphin. In the rat vas deferens assay, which is very specific for beta-endorphin, peptide 5 displays mixed agonist-antagonist activity. Most remarkably, peptide 5 displays a potent opiate analgesic effect when injected intracerebroventricularly into mice. At equal doses, the analgesic effect of peptide 5 is less than that of beta-endorphin (10-15%) but longer lasting. In conjunction with our previous model studies, these results clearly demonstrate that the amphiphilic helical structure in the C terminus of beta-endorphin is of predominant importance with regard to activity in rat vas deferens and analgesic assays. The similarity between the in vitro and in vivo opiate activities of beta-endorphin and peptide 5, when compared to the drastic change in chirality in the latter model, demonstrates that even a left-handed amphiphilic helix formed by D-amino acids can function satisfactorily as a structural unit in a beta-endorphin-like peptide.

Examination of the requirement for an amphiphilic helical structure in beta-endorphin through the design, synthesis, and study of model peptides.

In our approach to beta-endorphin modeling, we have proposed that the biological properties of the natural peptide are determined by the combination of three basic structural units: a highly specific opiate recognition sequence at the NH2 terminus (residues 1-5) connected via a hydrophilic peptide link (residues 6-12) to a potential amphiphilic helix in the COOH-terminal residues 13-31. In the alpha-helical conformation the hydrophobic domain twists around the length of the helix and covers almost one-half of its surface. The other distinctive features of the helix include its basicity and the two aromatic residues Phe18 and Tyr27. In contrast to previous models we have studied, peptide 4 is a "negative" model in the sense that it was designed and examined in order to determine how the lack of a well defined amphiphilic structure affects the biological properties of beta-endorphin. For this purpose, peptide 4 retains the three structural units previously postulated for beta-endorphin, but the amino acids of the 13-31 region are arranged in such a way that no definite continuous hydrophobic zone could be formed in an alpha- or pi-helical conformation of this region. In aqueous buffered solutions, peptide 4 showed almost the same amount of alpha-helical structure as beta-endorphin, with a slight tendency toward less helicity in 50% aqueous 2,2,2-trifluoroethanol. In rat brain homogenate, peptide 4 was degraded slightly slower than beta-endorphin, in contrast to the apparently much higher stability of previous models under the same conditions. With regard to opiate receptor binding, peptide 4 was twice as potent as beta-endorphin in mu-receptor assays but half as potent in delta-receptor assays. The opiate potency of peptide 4 on the guinea pig ileum was higher than that of beta-endorphin. In contrast, in the rat vas deferens assay, which is very specific for beta-endorphin, the potency of peptide 4 was very low and could be shown not to be mediated by the same opiate mechanism or by the same opiate receptor. A comparison of these results with those of previous model peptides provides further evidence for the importance of an amphiphilic helical structure in beta-endorphin residues 13-31, which determines the resistance to proteolysis of the natural molecule and contributes to the delta- and mu-opiate receptor interaction. The amphiphilicity of this helical structure must also be essential for high opiate activity on the rat vas deferens (epsilon-receptors), whereas no such structural requirement appears to be necessary for interaction with the opiate receptors on the guinea pig ileum.

[Methemoglobinemia in acute diarrhea in infants]. / Les méthémoglobinémies au cours des diarrhées aiguës du nourrisson.

8 cases of methemoglobinemia are observed in infants of 28 days to 138 days of age, who have all acute diarrhea. They are divided in two groups. --4 infants who have eaten for a long time a rich nitrate and nitrite content carrot soup. --4 cases of severe diarrhea with probable endogenous nitrification due to microbial proliferation. The methemoglobinemia level is here not very high and represents more a witness that an alarming symptom. Those infants are compared with 10 infants who have diarrhea without methemoglobinemia. Symptoms and treatment of methemoglobinemia are revisited.