A new genetic variant causing auditory neuropathy: A CARE case report.

INTRODUCTION: Auditory neuropathy refers to impaired synchronization of the auditory signal along the cochlear nerve. The present study, following CARE case report guidelines, describes a case of auditory neuropathy secondary to a genetic variant not previously described. OBSERVATION: An 18-year-old patient was followed for multiple learning disorder. His main complaint was speech comprehension, especially in noise. Auditory neuropathy was diagnosed on electrophysiological criteria, linked to a 2.66Mb deletion on the short arm of chromosome 16, at 16p13.11p12.3 (15,492,317-18,162,167, according to the hg19 version of the human reference genome). Adapted speech therapy sessions with auditory training for intelligibility in noise and a hearing aid with high-frequency microphone were prescribed. At 6months, the patient reported improvement in understanding speech in noise. CONCLUSION: The involvement of this 16p13.11 deletion in the patient's symptomatology was not obvious, in a probable context of incomplete penetrance and variable expression. Early diagnosis of auditory neuropathy allowed implementation of better adapted multidisciplinary specialized management.

[Severe allergic reaction due to a rectal enema]. / Réaction allergique sévère suite à un lavement.

Allergic drug reactions must always be considered when prescribing treatment, even in frequent pediatric problems such as acute abdominal pain due to constipation. We describe an original case of anaphylactic shock due to the administration of hypertonic rectal enema in a child. A 9-year-old child admitted to the emergency department for an acute complaint of abdominal pain related to constipation received an administration of a hypertonic rectal enema to allow the passage of stools. Afterwards, the child presented a life-threatening episode, requiring emergency treatment with transfer to the pediatric intensive care unit, suggesting an anaphylactic shock. The absence of any other drug or food intake, the chronology of events, and favorable outcome after treatment led to the diagnosis of a probable allergy to methylparaben, sodium parahydroxybenzoate, present as the excipient in the rectal enema. Anaphylactic shock is a serious allergic reaction, setting in rapidly, which may lead to fatal outcome. Most reactions to parabens reported concern, almost exclusively, the cutaneous application of paraben-containing topical preparations. The present observation underscores the original and undescribed risk of an allergic general reaction following the rectal administration of parabens. The indications of any prescription must be carefully observed and potential drug contraindications, considering the patient's history of allergy, should be sought.

[Ventricular fibrillation following deodorant spray inhalation]. / Fibrillation ventriculaire par inhalation de spray déodorant.

We report one case of out-of-hospital cardiac arrest with ventricular fibrillation following butane poisoning after inhalation of antiperspiration aerosol. An early management using semi-automatic defibrillator explained the success of the resuscitation. The mechanism of butane toxicity could be an increased sensitivity of cardiac receptors to circulating catecholamines, responsible for cardiac arrest during exercise and for resuscitation difficulties. The indication of epinephrine is discussed.

[Management of paediatric fever: is parents' skill appropriate?]. / Prise en charge de la fièvre de l'enfant: les connaissances et pratiques des parents sont-elles satisfaisantes?

UNLABELLED: Paediatric fever is a frequent reason of consulting a paediatrician or a general practitioner (30% of paediatric consultations). AIM OF THE STUDY: This investigation aimed at reporting the knowledge level concerning child's and infant's fever in a urban population and the resulting practices. Two thousand and six hundred questionnaires were distributed in June 2004 in the 29 scholar institutions of Metz agglomeration (France) classified in 3 categories according to socio-economical conditions of parents: 3 institutions of city centre (high socioeconomical conditions), 18 sub-urban institutions (intermediary conditions) and 8 institutions located in priority education zones (ZEP) (defavorable conditions). RESULTS: One thousand and thirty-eight questionnaires could be analyzed (40%): 176 in city centre, 634 in sub-urban zones and 228 in ZEP. Fever threshold at 38 degrees C is well-known and fever measuring methods used are mostly in accordance with the recommendations. The best room temperature was known and the use of antipyretic physical means underlined only a few cases of obvious mistakes. All parents were informed about worrying signs related with fever even if doctor's resort was excessive. Acetaminophen was the reference molecule before ibuprofen whereas the use of aspirin was decreasing. Antipyretic treatments methods used by parents were often unsuitable, leading to therapeutical inefficacy, overdosage or noxious drug interactions, mainly because of a lack of knowledge about drug components. CONCLUSION: This investigation underlines insufficient knowledge and noxious management practices among parents with unfavourable socio-economical conditions which lead us to recommend targeted information preferentially in areas gathering together most unfavourable socio-economical condition populations.

[Paediatric cardiac surgery and autoevaluation: risk score, complexity score and graphic analysis]. / Chirurgie cardiaque pédiatrique et auto-évaluation: score de risque, score de complexité et analyses graphiques.

The creation of a paediatric surgical unit requires autoevaluation in order to: assess the quality of the results with respect to recognised international standards, answer the family's questions about the results obtained and adhere to criteria of accreditation Between January 2003 and December 2004, 201 consecutive patients, children (N= 164) or operated for adult congenital heart disease (N= 37) were treated. No patient was excluded. The RACHS-1 risk score, the ARISTOTLE scores of complexity and performance and the CUSUM and VLAD graphic analyses were applied to the study of hospital mortality. An original "variable performance-adjusted display" (VPAD) graphic analysis was performed to show up any possible variations of performance. Paediatric hospital survival was 97.56% (95% CI: 93.9 - 99.1). The paediatric complexity and performance scores were 6.79 +/- 0.22 and 6.62 respectively. In the absence of statistical significance in this field of autoevaluation, graphic analyses indicated the performance of our unit with no "learning" curves. Graphic scores and analyses allow assessment of the function of a paediatric cardiac surgical unit and the variations of complexity with respect to time, before the appearance of statistical significance. The ARISTOTLE complexity and performance scores and their adaptation in VPAD seem to be more reliable and discriminating than the RACHS-1 score.

[Complications of prostaglandin E1 treatment of congenital heart disease in paediatric medical intensive care]. / Complications du traitement par prostaglandines E1 des cardiopathies congénitales en réanimation médicale pédiatrique.

The authors undertook a retrospective study of the modes of prescription, the tolerance and efficacy of prostaglandin E1 in 62 consecutive neonates with congenital heart disease (average Age 1.6 days: 35 boys: weight: 3.1 +/- 0.6 Kg) admitted to the paediatric intensive care unit of Nancy University Hospital between 1998 and 2002. The infusion time and cumulative dosage were 134 +/- 112 (6-480) hours and 111 +/- 94 (4-396) microg/Kg respectively. The side effects that were observed were: Apnoea (19%), abdominal distension (16%), bradycardia (13%), enterocolitis (6.5%), hypotension (6.5%), vomiting (5%), fever (1.6%) and skin rash (1.6%). Gastrointestinal disturbances are associated with a low body weight (p<0.04), to prolonged treatment (p<0.02) with no influence of initial or cumulative dosages (P=NS), with respiratory assistance (p<0.03) and longer hospital stay (p<0.01). Hypotension was commoner in cases of poor neonatal adaptation. Mortality was correlated with severe initial acidosis (p<0.02), a low Apgar score, the initial prolonged use of high doses of prostaglandin (p<0.04), and the presence of severe valvular aortic stenosis or hypoplasia of the left heart (p<0.002). The authors conclude that treatment with prostaglandin is effective in the majority of cases despite the use of low maintenance doses (0.01 microg/Kg/min). Gastrointestinal disturbances favourised by the perinatal context, the cardiac disease, and prolonged treatment are significant factors for morbidity and mortality. The beneficial role of early neonatal enteral feeding was not demonstrated in this high risk population.

[Kawasaki disease in newborns and infants: refractory forms to immunoglobulin therapy]. / Maladie de Kawasaki chez le nourrisson et l'enfant: formes réfractaires aux immunoglobulines.

UNLABELLED: We studied 52 consecutive patients with Kawasaki disease hospitalized (1984 -2003) during the acute phase (mean age 2.5 + 2.4 years; range 0.3 to 16 years, 34 males, 18 cases with coronary aneurysms, median follow-up 6.7 years), and identified a subgroup presenting a refractory subtype to immunoglobulin therapy. RESULTS: forty-nine infants benefited from a first regimen of immunoglobulins, 8.4 + 6 days following the onset of symptoms. Eleven infants (1.4 + 1.2 years, range 0.3 - 4.3 years, median 1.7 years) were non-responders, with coronary aneurysms in 8 cases (giant aneurysms (>8 mm) in 4 cases). These 11 infants were treated a second time by immunoglobulins, but 6 cases (1.8 + 1.6 years, with two cases of severe ventricular dysfunction and 2 cases of fatal myocardial infarction) required an additive therapy with (oral or IV route) corticosteroids (2) and cyclophosphamide bolus (4) with or without repetitive plasmapheresis (4). Non-responder patients had their treatment onset later (p<0.0003) using higher dosages (p<0.005), a longer delay for fever or biological signs correction (p<0.02), a worsening of coronary lesions (p<0.05) with more coronary secondary aneurysms (p<.005). The aneurysms, more frequent at the second phase of the disease (p<0.0001) are associated with: a younger age (p<0.03), a lower weight (p<0.02), a later onset of treatment (p<0.03), prolonged fever or inflammatory syndrome (p<0.05), higher level of fibrinogene (p<0.02). The overall mortality (5.7%) is correlated with giant aneurysms (p<0.001), myocardial ischemia (p<0.0001), heart failure (p<0.0001), and lack of early response to treatment (p<0.003). CONCLUSION: immunoglobin therapy can be repeated. In case of severe forms, the use of corticosteroids, cyclophosphamide and plasmapheresis may be proposed.

[Domiciliary assisted ventilation in children]. / Ventilation assistée à domicile chez l'enfant.

The concept of assisted ventilation in the home setting has greatly progressed as a routine practice. This technique was used from 1990 to 2000 in 16 children cared for at our center. Ten children had neuromuscular disease (infantile spinal amyotrophy 6, Duchenne myopathy 3, and mitochondrial myopathy 1) or other conditions including central hypoventilation (n = 2), traumatic tetraplegia (n = 2), encephalopathy with chronic bronchitis (n = 1) and bronchopulmonary dysplasia (n = 1). Only 5 children had a tracheotomy, the others were treated successfully with non-invasive ventilatory assistance. Initialization of non-invasive ventilatory assistance had been planned before development of respiratory failure in 4 of the 11 children, but generally was indicated after an episode of acute respiratory distress. Home ventilation, particularly with non-invasive assistance is a reliable method for long-term treatment of chronic alveolar hypoventilation in children. The appropriate time for initiating this therapy should be better defined.

Methacholine-induced volume dependence of respiratory resistance in preschool children.

Enhanced negative volume dependence of airway resistance is associated with bronchoconstriction in tracheostomized paralysed open-chest animals. Significant upper airways responses may be associated with bronchoconstriction and could thereby alter the pattern of volume dependence in spontaneously breathing subjects. The aim of the study was to test whether volume dependence of respiratory resistance (Rrs) could be demonstrated in preschool children undergoing routine methacholine challenge. The volume dependence of respiratory oscillation resistance at 12 and 20 Hz (Rrs,12 and Rrs,20) was examined in eight 4-5.5-yr-old children showing a positive response to methacholine. Multiple linear regression analysis was also used to account for flow dependence during tidal breathing (Rrs,12 or Rrs,20=K1+K2¿V'¿+K3V). Rrs,12 and Rrs,20 yielded similar results. Negative volume dependence was present at baseline and significantly enhanced by methacholine (p<0.01). For instance, the mean+/-SD inspiratory K3 at 20 Hz was 4.1+/-1.3 hPa x s x L(-2) at baseline and -15.0+/-4.3 hPa x s x L(-2) after methacholine, in which case it was also larger on expiration than on inspiration (p<0.05), possibly as a result of upper airway responses. A significant increase in the negative volume dependence of respiratory resistance may thus be shown in preschool children in response to methacholine. The volume dependence (K3) during inspiration may be particularly useful in detecting bronchoconstriction, because it is less likely to be affected by upper airway mechanisms than during expiration.

Effect of increased brain GABA concentrations on breathing in unanesthetized newborn rabbits.

Evidence suggests that gamma-aminobutyric acid (GABA) is involved in control of breathing and in the hypoxia-related ventilatory depression in newborns. However, this evidence is obtained mainly from studies on anesthetized animals. Because anesthesia may interfere with the GABA system, the objectives of our study were to examine effects of GABA on ventilation (V(E)) and ventilatory response to hypoxia and to reveal effects of repeated hypoxia on GABA concentrations in unanesthetized newborns. The study was performed in rabbits in two age groups: 1-3 days old (group I) and 10-14 days old (group II). To increase brain endogenous GABA concentrations, rabbits were injected with an inhibitor of GABA transaminase, aminooxyacetic acid (AOAA; 20 mg/kg i.p.). To prevent postmortem formation of GABA, at the end of experiments the rabbits received an inhibitor of glutamic acid decarboxylase, IP-3-mercaptopropionic acid (100 mg/kg i.p.). Animals were studied in normoxia alone, or they were exposed for 15 min to 8% O(2) before and 10 and 35 min after saline or AOAA. GABA concentrations were measured in brainstem, cerebrum, and cerebellum by means of a capillary electrophoresis. In group I, AOAA had no respiratory effects. In group II, AOAA decreased V(E), tidal volume, and mean inspiratory flow in normoxia and reversed V(E) decline during hypoxia 10 min after the injection, GABA concentrations were not age dependent and the highest in the brainstem. Repeated hypoxia increased the cerebellar GABA concentrations and had no effect in group I. These results imply that in unanesthetized rabbits, GABAergic neurotransmission in the respiratory control network becomes functional by the 2nd week of life, but it does not contribute to the biphasic ventilatory response to moderate hypoxia. In contrast, GABA-evoked block of the cerebellar inhibitory input during hypoxia may be responsible for the reversal of the V(E) decline in unanesthetized newborns.

Sequential activation of activator protein-1-related transcription factors and JNK protein kinases may contribute to apoptotic death induced by transient hypoxia in developing brain neurons.

Previous studies have demonstrated that transient hypoxia (6 h) induces apoptotic death in cultured neurons isolated from the fetal rat forebrain. Since activation of c-Jun N-terminal kinases (JNKs) and subsequent phosphorylation of c-Jun are suspected to be involved in the apoptotic pathway in several cell types, the time course of activator protein-1 (AP-1) DNA-binding, in line with induction of the AP-1 components and JNK activation, was examined during hypoxia/reoxygenation in the same model. Gel shift analysis depicted the presence of functional AP-1 transcription factors in both control and hypoxic neurons. One hour after the onset of hypoxia, all AP-1 components were markedly overexpressed. They include c-Jun, Jun B, Jun D, c-Fos and Fos-related antigens. Whereas, only c-Jun remained elevated for up to 96 h post-reoxygenation, time at which neurons were injured, other gene products showed patterned induction/repression as hypoxia progressed and then during the post-reoxygenation period, with Fos-related antigens being finally induced at 96 h. Only JNK1 was constitutively detected in cultured neurons, and its expression was inhibited during hypoxia. Nonetheless, both JNK1 and JNK3 were markedly, but transiently, induced at 48 h post-reoxygenation, when apoptosis-related morphological features became apparent. These data support the hypothesis that transient hypoxia, independently of ischemia, may trigger apoptosis through JNK signaling pathway in developing brain neurons.

Maturation of B cells in the lamina propria of human gut and bronchi in the first months of human life.

Little is known of the maturation of the mucosae-associated lymphoid tissue (MALT) in man, because, for ethical reasons, tissues from newborns are not easy to obtain. We used the opportunity provided by autopsies systematically performed in infants who died of Sudden Infant Death Syndrome (SIDS) to study the maturation of the MALT after birth. Gut and bronchus samples of 90 infants from postpartum to 90 months and who died from SIDS were collected and studied by histological and immunofluorescence examination. Plasma cells, absent at birth, appeared within a few hours after birth and initially were of the IgM isotype. IgA plasma cells appeared at 12 days. These cells were first observed in gut and later in bronchi, indicating that maturation of the gut precedes that of bronchi. The number of plasma cells increased rapidly over time and IgA plasma cells became predominant after 3 weeks in the gut and 6 weeks in bronchi. At birth, only small IgM bearing B-cell foci were seen and organized germinal centers appeared to develop over a few days, first in the gut and only later in bronchi. These results confirm that, in man, the MALT organization at birth is still in its fetal form and that maturation depends on intestinal challenges and evolves over several weeks before IgA becomes the predominant isotype secreted.

[Diagnosis of post-operative venous thrombosis using determination of plasma D-dimer]. / Diagnostic des thromboses veineuses post-chirurgicales par le dosage des D-dimères plasmatiques.

PURPOSE: The D-Dimer test has been shown to be highly sensitive for the diagnosis of deep vein thrombosis (DVT) and pulmonary embolism. Two automatic quantitative tests giving a rapid response within 10 and 30 minutes have been recently marketed. In the postsurgery situation however, the role of the D-Dimer test remains controversial and the optimal cutoff value remains open. The aim of this study was to determine the cutoff value during the postoperative period. PATIENTS AND METHODS: One hundred three consecutive patients admitted to surgery were included. In all patients, D-Dimer test was performed every 2 or 4 days from admission to hospital discharge. The Vidas D-Dimer (Biomerieux, Marcy l'Etoile, France) and the STA Liatest D-DI (Diagnostica Stago, Asnières, France) were performed in parallel in all cases. RESULTS: Thirty-five patients were excluded because the follow-up period was too short. Results suggest that a D-Dimer value below 2 micrograms/ml has a negative predictive value of 100%. A D-Dimer value over 4 micrograms/ml would indicate suspected deep vein thrombosis in half of the cases, even without clinical signs. Dividing the patients into three groups according to the D-Dimer value, the two tests correlated poorly (r = 0.36 and 0.57) in the middle group (between 2 and 3 and between 3 and 4) and correctly for values below 2 or over 4 micrograms/ml (r = 0.83 and 0.78 respectively). CONCLUSION: These two optimum cutoff values (< 2 micrograms/ml and > 4 micrograms/ml) are useful for determining the need for further explorations for DVT. By limiting need for ultrasonography and contrast venography, the cost-efficacy ratio for the detection of DVT during the postoperative period is greatly improved with the D-Dimer screening strategy.

Respiratory oscillation mechanics in infants with bronchiolitis during mechanical ventilation.

The aim of the study was to describe the pattern of respiratory oscillation mechanics and responses to positive end-expiratory pressure (PEEP) in bronchiolitis. Six infants were studied during the course of mechanical ventilation. A 20 Hz sinusoidal pressure variation was applied at the endotracheal tube where flow was measured with a pneumotachograph. Resistance and reactance obtained from the complex pressure-flow ratio were separated during inspiration (R(rs,i); X(rs,i)) and expiration (R(rs,e); X(rs,e)), and the differences between R(rs,i) and R(rs,e) (deltaR(rs)) and X(rs,i) and X(rs,e) (deltaX(rs)) were calculated. The data were corrected for the mechanical characteristics of the endotracheal tube. The measurements were repeated while PEEP was varied between 0 and 8 hPa. Two infants were found to have normal R(rs) and near-zero X(rs) and both parameters exhibited little change within the respiratory cycle or with varying PEEP. Four infants had high R(rs) at zero PEEP. In two, R(rs,i) was markedly elevated (108.5 and 85.2 hPa.s/L, respectively), and X(rs,i) was markedly negative (-25.0 and -22.5 hPa.s/L, respectively) at zero PEEP, while deltaR(rs) and deltaX(rs) were small. R(rs,i) and the absolute value of X(rs,i) decreased with increasing PEEP. This pattern of oscillation mechanics was consistent with low lung volumes and atelectasis, being reversed by increasing PEEP. In the remaining two subjects, R(rs,i) was moderately elevated (57.8 and 53.6 hPa.s/L, respectively) and X(rs,i) moderately negative (-12.5 and -7.7 hPa.s/L, respectively) at zero PEEP. DeltaR(rs) (-59.8 and -56.5 hPa.s/L, respectively) and delta(rs) (28.1 and 48.7 hPa.s/L, respectively) were large, but were dramatically reduced by increasing PEEP. These patterns were consistent with expiratory airflow limitation. Measurements of respiratory impedance are, therefore, informative in regard to the pathophysiological mechanisms occurring in bronchiolitis during mechanical ventilation, and they may be helpful in setting the level and assessing the effect of PEEP.

Pharmacology of respiratory control in neonates and children.

The therapeutic approach of respiratory control disorders in neonates and young children is based on a clear understanding of the mechanisms involved in the regulation of ventilation according to the stages of postnatal development. A complete evaluation of drugs presenting either depressive or stimulative effects on ventilation is required.