Audiovestibular consequences of congenital cytomegalovirus infection.

Congenital cytomegalovirus (CMV) infection is the second most frequent cause of mental retardation and sensorineural hearing loss, after genetic factors. Recently, pediatric forensic and fetopathological studies have led to progress in understanding the pathophysiological mechanisms underlying the various neurosensory sequelae. Thanks to the identification of certain prognostic factors of hearing loss, therapeutic protocols based on antiviral molecules are now proposed for target populations. This treatment has shown efficacy in limiting hearing threshold deterioration and even, in some cases, seems to provide partial recovery of hearing in symptomatic congenitally infected CMV neonates. However, optimal treatment duration and administration modalities are not clearly defined. This article reviews recent data concerning audiovestibular sequelae and their management in children congenitally infected by CMV.

Pseudohypacusis in children: circumstances and diagnostic strategy.

OBJECTIVES: The study attempts to specify the circumstances under which we should pay attention to children's pseudohypacusis. It evaluates the methods used to detect such cases and to determine hearing thresholds, according to the uni-or bilateralism of hearing loss. The study finally deals with the future of children diagnosed with pseudohypacusis. METHODS: The study was retrospective from January 1993 to November 2011 and prospective from December 2011 to April 2012. We included all the children between 3 and 16 years who were diagnosed with pseudohypacusis. We observed the reasons for them to consult, whether they had already been tested or had treatment, and what kind of hearing loss they displayed. All children were tested using standard pure tone audiometry and speech audiometry. Depending on the first results, other tests were conducted. They included transient evoked otoacoustic emissions (TEOEs), auditory brainstem responses (ABR) and auditory steady state responses. Families were finally contacted by phone over April 2012 in order to let them know about their child's results. RESULTS: Fifty-four children were included: 19 boys and 35 girls, with an average age of 10 year-old (±3). The simulated hearing loss (HL) was bilateral (36), unilateral (18), of perception (37), moderate HL (33), cophosis (5). Fifteen cases were linked to a family or personal history of hearing loss, while 27 cases were due to important events like adoption, abuse, verbal aggression, school problems. Before diagnosing a pseudohypacusis, 13 children had had imaging studies, 3 had been treated with corticosteroids, and 5 had hearing aids. Most of the time the presence of pseudohypacusis was suspected a discrepancy between speech reception and air-conduction pure tone thresholds, as shown by the medical test (answer on whispered voice). The diagnosis was confirmed by ABR or TEOEs, except in cases where clinic was obvious. Then family's patient and patient were reassured and informed. An audiological follow-up during either 6 months or 1 year was proposed, as well as a psychological consultation. CONCLUSION: Complementary examinations have to be performed to rule out a pseudohypacusis case before suggesting an invasive or expensive treatment (surgery or hearing aids) of children.

[Retrospective evaluation of short tympanostomy tubes efficacy in case of recurrent acute otitis media on an infant population]. / Evaluation rétrospective de l'efficacité des aérateurs trans-tympaniques courts en cas d'otites moyennes aiguës récidivantes chez le nourrisson.

INTRODUCTION: The aim of this study is to appreciate the results of short-tympanostomy tubes (ST) in case of recurrent acute otitis media (AOM), and to appreciate the risk factors of recurrent AOM. METHODS: This retrospective chart study concerns infants who had STT placement surgery forrecurrent AOM, between 2007 and 2011. Demographic data, anamnesis, efficacy and postoperative follow-up were analyzed. RESULTS: Forty-nine children were included in the study (30 boys, 19 girls; 7 months to 2 years-old, median age 1.4 year). Two-thirds attended a day-care center, one third was an onlychild. One quarter had an anemia. Anti-Haemophilus and anti-pneumococcus vaccinations were up-to-date in 87.5%. After STT placement, 20 children (40.8%) did not present any new episode of AOM. This result did not vary with adenoidectomy. Among the ones that relapsed AOM after STT, 48.3% presented with only one episode. For two thirds of the patients, no general antibiotic treatment was necessary as long as the STT were in place. Half STT have been spontaneously expulsed between 6 and 12 months. Thirteen infants (37.1%) had new episodes of AOM after STT expulsion and 5 (38.5%) needed new tube placement. CONCLUSION: This study confirms that day care and siblings are risk factors of recurrent AOM, but does not confirm potential role of the anemia. STT placement decreased effectively AOM recurrences, their severity and the need for antibiotics prescriptions. No residual perforation was encountered in this study.

Pandemic influenza A (H1N1) 2009 in the English- and Dutch-speaking Caribbean an epidemiological overview / Pandemia de gripe A (H1N1) de 2009 en el Caribe de habla inglesa y holandesa: panorama epidemiológico

OBJECTIVE: To describe epidemiological trends of pandemic influenza A (H1N1) in the English- and Dutch-speaking Caribbean during the pandemic period. DESIGN AND METHODS: Data on laboratory-confirmed cases and deaths associated with pandemic influenza A (H1N1) contained in two regional databases at the Caribbean Epidemiology Centre (CAREC) were analysed. The data sources were epidemiological and laboratory reports from English- and Dutch-speaking countries and the CAREC laboratory information system (LABIS). RESULTS: In the English- and Dutch-speaking Caribbean, pandemic influenza A (H1N1) was the predominant circulating influenza virus type during the pandemic period. There were three distinct phases: a first pandemic wave during mid-April to end of August 2009 (734 cases), a second pandemic wave during September-December 2009 (570 cases) and a phase of low transmission during January to mid-August 2010 (55 cases). The majority of cases (76%) were aged less than 30 years, with children of school age being most affected. Most cases (89%) presented with symptoms of the respiratory tract and smaller proportions (20-40%) presented with gastrointestinal and other symptoms. No cases tested were resistant to oseltamivir. A quarter of cases required hospitalization and the case fatality rate was 1.8%. CONCLUSIONS: The epidemiological characteristics of the pandemic in the English- and Dutch-speaking Caribbean were consistent with that in other parts of the world. It is important that post pandemic surveillance (epidemiological and virological) for respiratory illnesses continues to be enhanced in order to give a better understanding of seasonality and changing trends in respiratory illnesses and their aetiologic agents.

OBJETIVO: Describir las tendencias epidemiológicas de la pandemia de gripe A (H1N1) en el Caribe de habla inglesa y holandesa durante el periodo pandémico. DISEÑO Y MÉTODOS: Se analizaron los datos sobre casos confirmados por laboratorio y muertes asociadas con la pandemia de gripe A (H1N1), contenidos en dos bases de datos regionales del Centro Epidemiológico del Caribe (CAREC). Las fuentes de los datos fueron los reportes epidemiológicos y de laboratorio de los países de habla inglesa y holandesa, así como del Sistema de Información de Laboratorio del CAREC (LABIS). RESULTADOS: En el Caribe anglófono y de habla holandesa, la pandemia de gripe A (H1N1) fue el tipo de virus de gripe que circuló predominante durante el periodo pandémico. Hubo tres fases distintas: una primera ola pandémica desde mediados de abril a finales de agosto de 2009 (734 casos); una segunda ola pandémica en septiembre-diciembre de 2009 (570 casos); y una fase de baja transmisión de enero a mediados de agosto de 2010 (55 casos). La mayoría de los casos (76%) tenían menos de 30 años, siendo los niños de edad escolar los más afectados. La mayor parte de los casos (89%) presentaban síntomas de las vías respiratorias, y un número menor (20-40%) presentaban síntomas gastrointestinales y otros síntomas. Ninguno de los casos sometidos a prueba resultó resistente al oseltamivir. Una cuarta parte de los casos requirió hospitalización, y la tasa de letalidad fue de 1.8%. CONCLUSIONES: Las características epidemiológicas de la pandemia en el Caribe de habla inglesa y holandesa concuerdan con las encontradas en otras partes del mundo. Es importante continuar mejorando la vigilancia postpandémica (epidemiológica y virológica) de las enfermedades respiratorias, con el fin de lograr una mejor comprensión de la estacionalidad y las tendencias cambiantes de las enfermedades respiratorias y sus agentes etiológicos.

Pandemic influenza A (H1N1) 2009 in the English- and Dutch-speaking Caribbean: an epidemiological overview.

OBJECTIVE: To describe epidemiological trends of pandemic influenza A (H1N1) in the English and Dutch-speaking Caribbean during the pandemic period. DESIGN AND METHODS: Data on laboratory-confirmed cases and deaths associated with pandemic influenza A (H1N1) contained in two regional databases at the Caribbean Epidemiology Centre (CAREC) were analysed. The data sources were epidemiological and laboratory reports from English and Dutch-speaking countries and the CAREC laboratory information system (LABIS). RESULTS: In the English- and Dutch-speaking Caribbean, pandemic influenza A (H1N1) was the predominant circulating influenza virus type during the pandemic period. There were three distinct phases: a first pandemic wave during mid-April to end of August 2009 (734 cases), a second pandemic wave during September-December 2009 (570 cases) and a phase of low transmission during January to mid-August 2010 (55 cases). The majority of cases (76%) were aged less than 30 years, with children of school age being most affected. Most cases (89%) presented with symptoms of the respiratory tract and smaller proportions (20-40%) presented with gastrointestinal and other symptoms. No cases tested were resistant to oseltamivir. A quarter of cases required hospitalization and the case fatality rate was 1.8%. CONCLUSIONS: The epidemiological characteristics of the pandemic in the English- and Dutch-speaking Caribbean were consistent with that in other parts of the world. It is important that post pandemic surveillance (epidemiological and virological) for respiratory illnesses continues to be enhanced in order to give a better understanding of seasonality and changing trends in respiratory illnesses and their aetiologic agents.

Endoscopic balloon dilatation of esophageal strictures in children.

AIM OF THE STUDY: To assess the efficacy and safety of endoscopic balloon dilatation of esophageal strictures in children. DESIGN: retrospective case series; population: 49 patients under 18 years of age referred to our center for esophageal strictures; treatment: endoscopic balloon dilatation; outcome parameters: residual dysphagia, weight gain, iatrogenic esophageal perforation, assessment of the esophageal lumen by endoscopy or esophagogram. RESULTS: The three main etiologies were esophageal atresia (49%; n=24), corrosive injury (25%; n=12), and epidermolysis bullosa (14%; n=7), followed by a heterogeneous group of rarer causes (12%; n=6). The number of dilatations ranged from 1 to 8 sessions per patient (median ± SEM: 2 ± 0.3). The length of the follow-up period ranged from 20 to 109 months (median ± SEM: 40 ± 4 months). Treatment was successful in 86% of cases (n=42). Twelve percent of patients (n=6) had a residual stenosis requiring surgery, and a further one still experienced swallowing difficulties requiring enteral nutrition via gastrostomy in spite of the absence of significant residual stricture. Results were less satisfactory in cases of corrosive injury than with other etiologies. Three esophageal perforations were observed (6% of patients; 2% of procedures). All were medically treated. CONCLUSIONS: Endoscopic balloon dilatation is a simple, safe and efficacious treatment of esophageal strictures in children.

Acute mastoiditis in children: a retrospective study of 188 patients.

OBJECTIVE: The aim of this study is to define the clinical and bacteriological characteristics of acute mastoiditis (AM) in children in order to optimize diagnostic work-up and treatment. METHODS: In this retrospective study, 188 children between 3 months and 15 years of age (15±24 months; median±SD) were referred to our pediatric ENT emergency center for AM during a 7-year period (December 2001-January 2008). RESULTS: Fifty seven percent were male and 43% were female. Clinical follow-up duration was 3.9±0.7 months (mean±SEM). The incidence of AM remained stable during the whole study period. Microbiological samples (n=236) were negative in 33% of cases. The most frequently isolated germs were Streptococcus pneumoniae (51%), Streptococcus pyogenes (11.5%), Anaerobes (6.5%), and coagulase-negative Staphylococcus (6.5%). Paracentesis, puncture of retro auricular abscess under local anesthesia, and peroperative samples all contributed to isolate the involved germ(s). All the patients were hospitalized and received intravenous antibiotics, and 36.2% (n=68) underwent surgery. Several surgical procedures were necessary in 4 cases (2.1%). AM recurrences requiring a second hospitalization were observed in 8 patients (4.3%). The only observed complication was lateral sinus thrombosis (n=6; 3.2%). Surgical failures, requiring more than one surgical procedure, were more frequent in case of: (i) presence of Anaerobes (p≤0.001) or Gram-negative bacteria (p≤0.05) in microbiological samples; (ii) surgical drainage without mastoidectomy (p≤0.001). Recurrences were more frequent in AM due to Streptococcus pneumoniae. CONCLUSIONS: Based on our findings and on literature data, a protocol was established in order to standardize the management of pediatric AM in our center. The mains points are: no systematic surgery; if surgery is indicated, it must encompass a mastoidectomy; broad-spectrum intravenous antibiotic treatment covering the most commonly involved germs (3rd generation cephalosporin) and secondarily adapted to the results of microbiological samples. If the infection is not controlled after 48 h of intravenous antibiotherapy, a mastoidectomy had to be performed.

Long term results of ossiculoplasties with partial and total titanium Vario Kurz prostheses in children.

OBJECTIVE: To assess and compare the efficacy of the Kurz titanium prostheses for total or partial ossicular reconstruction in children. PATIENTS AND METHODS: Retrospective chart review was performed for 71 consecutive children who underwent 74 ossicular reconstructions with Kurz prostheses between December 1999 and October 2007 (27 PORP and 47 TORP). Audiological parameters using four-frequency averages (0.5, 1, 2 and 4 kHz) were assessed pre- and postoperatively. Clinical and audiometric follow-up times were respectively 33±18.6 and 30±17.7 months (mean±SD). RESULTS: Fifty-two percent of all patients achieved an air bone gap (ABG) ≤20 dB, 53.8% in the PORP group and 51.1% in the TORP group. The improvement of the mean ABG was 13.3 dB, 9.4 dB for PORP and 14.6 dB for TORP. Overall mean pure tone averages improved 13.2±1.8 dB (mean±SEM) with 10±2.7 dB for PORP and 15±2.4 dB for TORP. The sensory neural hearing loss rate was 1.4% (one TORP) and the extrusion rate was 2.7% (n=2/74). CONCLUSION: The success rate (ABG≤20 dB) and the pure tone averages were not different between PORP and TORP. Kurz titanium ossicular prostheses offer high biocompatibility and high stability with low complication rates in pediatric ossicular reconstruction.

p53 compound heterozygosity in a severely affected child with Li-Fraumeni syndrome.

The Li-Fraumeni Syndrome (LFS) is a rare, dominantly inherited syndrome that features high risk of cancers in childhood and early adulthood. Affected families tend to develop bone and soft tissue sarcomas, breast cancers, brain tumors, leukemias, and adrenocortical carcinomas. In some kindreds, the genetic abnormality associated with this cancer phenotype is a heterozygous germline mutation in the p53 tumor suppressor gene. Recently, we identified one patient who presented in early childhood with multiple primary cancers and who harbored three germline p53 alterations (R156H and R267Q on the maternal allele and R290H on the paternal allele). To classify the biologic effects of these alterations, functional properties of each of the p53 mutants were examined using in vitro assays of cellular growth suppression and transcriptional activation. Each amino acid substitution conferred partial or complete loss of wild-type p53 function, but the child completed normal embryonic development. This observation has not been previously reported in a human, but is consistent with observations of normal embryogenesis in p53-deficient mice.

Genetic predisposition to cancer and familial cancer syndromes.

Approximately 10% to 15% of childhood cancers are hereditary or familial in nature. For several genetic disorders, the development of cancer is a secondary manifestation of the clinical phenotype, whereas cancer predisposition syndromes are generally recognized by the manifestation of characteristic malignancies. The study of pediatric cancer and rare hereditary cancer syndromes and associations has led to the identification of numerous cancer genes that are known to play critical roles in both normal and abnormal cellular growth, differentiation, and proliferation. The potential to identify such genetic markers of cancer predisposition poses difficult social, legal, and ethical questions in their application to clinical practice.

Cysteine-containing peptide sequences exhibit facile uncatalyzed transacylation and acyl-CoA-dependent acylation at the lipid bilayer interface.

A variety of simple cysteine-containing lipopeptides, with sequences modeled on those found in naturally occurring S-acylated proteins, undergo spontaneous S-acylation in phospholipid vesicles at physiological pH when either long-chain acyl-CoAs or other S-acylated peptides are added as acyl donors. Fluorescent or radiolabeled lipopeptides with the sequence myristoyl-GCX- (X = G, L, R, T, or V), a motif found to undergo S-acylation in several intracellular regulatory proteins, and the prenylated peptide -SCRC(farnesyl)-OMe, modeled on the carboxyl terminus of p21H-ras, were all found to be suitable acyl acceptors for such uncatalyzed S-acyl transfer reactions at physiological pH. Acylation of these cysteinyl-containing lipopeptides to high stoichiometry was observed, on time scales ranging from a few hours to a few tens of minutes, in vesicles containing relatively low concentrations (< or = mol %) and only a modest molar excess (2.5:1) of the acyl donor species. No evidence was obtained for acyl transfer to peptide serine or threonine hydroxyl groups under the same conditions. These observations may have significant implications both for the design of in vitro studies of the S-acylation of membrane-associated proteins and for our understanding of the mechanisms of S-acylation of these species in vivo.