RESUMO
Crouzon craniofacial dysostosis (CFD) is an autosomal dominant craniofacial disorder characterized by premature craniosynostosis, shallow orbits and hypoplastic maxilla. To map the gene responsible, we have used a mapping strategy of testing for linkage to known developmental genes. Analysis of a large kindred established linkage between CFD and three loci (D10S190, D10S209 and D10S216) that span a 13 cM region on chromosome 10q. A maximum pairwise lod score of 4.42 (theta = 0) at D10S190 was obtained and the addition of a second kindred produced a combined pairwise lod score of 5.32 (theta = 0) at the same locus. The developmental gene, PAX2, located within this region, is an attractive candidate gene.
Assuntos
Cromossomos Humanos Par 10 , Disostose Craniofacial/genética , Mapeamento Cromossômico , Disostose Craniofacial/patologia , Feminino , Genes Dominantes , Ligação Genética , Marcadores Genéticos , Humanos , Escore Lod , Masculino , Linhagem , FenótipoRESUMO
Hereditary pancreatitis (HP) is a rare, early-onset genetic disorder characterized by epigastric pain and often more serious complications. We now report that an Arg-His substitution at residue 117 of the cationic trypsinogen gene is associated with the HP phenotype. This mutation was observed in all HP affected individuals and obligate carriers from five kindreds, but not in individuals who married into the families nor in 140 unrelated individuals. X-ray crystal structure analysis, molecular modelling, and protein digest data indicate that the Arg 117 residue is a trypsin-sensitive site. Cleavage at this site is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis.
Assuntos
Genes/genética , Pancreatite/genética , Mutação Puntual/genética , Tripsinogênio/genética , Arginina/fisiologia , Cromossomos Humanos Par 7 , Análise Mutacional de DNA , Ativação Enzimática , Éxons/genética , Feminino , Heterozigoto , Humanos , Masculino , Modelos Moleculares , Linhagem , Polimorfismo de Fragmento de Restrição , Conformação Proteica , Estrutura Terciária de Proteína , Tripsina/metabolismo , Tripsinogênio/químicaRESUMO
Biofilms of pathogenic bacteria are present on the middle ear mucosa of children with chronic otitis media (COM) and may contribute to the persistence of pathogens and the recalcitrance of COM to antibiotic treatment. Controlled studies indicate that adenoidectomy is effective in the treatment of COM, suggesting that the adenoids may act as a reservoir for COM pathogens. To investigate the bacterial community in the adenoid, samples were obtained from 35 children undergoing adenoidectomy for chronic OM or obstructive sleep apnea. We used a novel, culture-independent molecular diagnostic methodology, followed by confocal microscopy, to investigate the in situ distribution and organization of pathogens in the adenoids to determine whether pathogenic bacteria exhibited criteria characteristic of biofilms. The Ibis T5000 Universal Biosensor System was used to interrogate the extent of the microbial diversity within adenoid biopsy specimens. Using a suite of 16 broad-range bacterial primers, we demonstrated that adenoids from both diagnostic groups were colonized with polymicrobial biofilms. Haemophilus influenzae was present in more adenoids from the COM group (P = 0.005), but there was no significant difference between the two patient groups for Streptococcus pneumoniae or Staphylococcus aureus. Fluorescence in situ hybridization, lectin binding, and the use of antibodies specific for host epithelial cells demonstrated that pathogens were aggregated, surrounded by a carbohydrate matrix, and localized on and within the epithelial cell surface, which is consistent with criteria for bacterial biofilms.
Assuntos
Tonsila Faríngea/microbiologia , Bactérias/classificação , Bactérias/patogenicidade , Biodiversidade , Biofilmes/crescimento & desenvolvimento , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Técnicas Bacteriológicas/métodos , Criança , Pré-Escolar , Feminino , Humanos , Hibridização in Situ Fluorescente/métodos , Lactente , Masculino , Microscopia Confocal , Técnicas de Diagnóstico Molecular/métodosRESUMO
INTRODUCTION - The mechanisms underlying craniosynostosis remains unknown. However, mutations in FGFR2 are associated with craniosynostotic syndromes. We previously compared gene expression patterns of patent and synostosing coronal sutures in the nude rat and demonstrated down regulation of Noggin in synostosing sutures. Noggin expression is also suppressed by FGF2 and constitutive FGFR2 signaling [Warren et al. (2003) Nature, vol. 422, pp. 625-9; McMahon et al. (1998) Genes Dev, vol. 12, pp. 1438-52]. Thus, we therefore hypothesized that the addition of rhNoggin to prematurely fusing sutures should prevent synostosis. MATERIALS AND METHODS - Cohorts of nude rats were subjected to: 1) surgical elevation of the coronal suture (shams); 2) surgical elevation and placement of normal or FGFR2 mutant human osteoblasts onto the underlying dura (xenotransplants); or 3) xenotransplantation with co-application of heparin acrylic beads soaked with recombinant human (rh) Noggin. Eleven days post-surgery the sutures were harvested, stained, and histologically examined. RESULTS - Animals that received control osteoblasts, sham surgery, or no surgery demonstrated normal skull growth and coronal suture histology, whereas animals transplanted only with FGFR2 mutant osteoblasts showed evidence of bridging synostosis on the calvarial dural surface. Sutures treated with FGFR2 mutant osteoblasts and rhNoggin remained patent. CONCLUSION - The chimeric nude rate model is a viable model of craniosynostosis. FGFR2 mutations in osteoblasts induce bridging osteosynthesis demonstrating one of the mechanisms for premature suture fusion. Topical application of rhNoggin protein prevents craniosynostosis in the weanling nude rat xenotransplantation model of syndromic craniosynostosis.
Assuntos
Proteínas Morfogenéticas Ósseas/antagonistas & inibidores , Proteínas de Transporte/uso terapêutico , Craniossinostoses/prevenção & controle , Motivos Nó de Cisteína , Acrocefalossindactilia/genética , Acrocefalossindactilia/patologia , Animais , Linhagem Celular , Linhagem da Célula , Quimera , Suturas Cranianas/patologia , Suturas Cranianas/cirurgia , Disostose Craniofacial/genética , Disostose Craniofacial/patologia , Modelos Animais de Doenças , Dura-Máter/cirurgia , Osso Frontal/patologia , Osso Frontal/cirurgia , Humanos , Mutação/genética , Osteoblastos/transplante , Osso Parietal/patologia , Osso Parietal/cirurgia , Ratos , Ratos Nus , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Proteínas Recombinantes , Crânio/crescimento & desenvolvimento , Transplante HeterólogoRESUMO
OBJECTIVE: Multiple sclerosis (MS) is a disabling idiopathic inflammatory disorder with evidence of immune dysfunction. Current therapies for MS include preparations of beta-interferon (beta IFN). We studied the gene expression patterns in peripheral blood mononuclear cells from relapsing-remitting MS patients undergoing weekly beta IFN-1a therapy (Avonex; 30 mg intramuscular) to identify biomarkers for beta IFN responsiveness. METHODS: Oligonucleotide microarrays were used for the comparative analysis of gene expression patterns from longitudinal PBMC samples taken from five patients undergoing beta IFN therapy. RESULTS: On the basis of two-fold changes in expression levels and statistical analyses we selected a candidate diagnostic set of 136 genes that were differentially expressed between pretreatment and IFN-beta-1a-treated MS patients. When we applied this gene set to cluster the specimens according to their expression profiles, the pretreatment samples clustered in one branch, and acute and chronic samples following treatment clustered in another branch. However, the chronic samples from the single clinical non-responder clustered with the pretreatment branch, suggesting that a possible reversal of beta IFN-induced gene expression may be contributing to the poor clinical response. CONCLUSIONS: These 136 genes represent potential targets for new MS therapeutics and the basis for lack of beta IFN response.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Interferon beta/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Esclerose Múltipla Recidivante-Remitente/patologia , Adulto , Análise por Conglomerados , Perfilação da Expressão Gênica/métodos , Humanos , Fatores Imunológicos/uso terapêutico , Interferon beta/uso terapêutico , Análise em Microsséries/métodos , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológicoRESUMO
The human fibroblast growth factor receptor (FGFR) genes play important roles in normal vertebrate development. Mutations in the human FGFR2 gene have been associated with many craniosynostotic syndromes and malformations, including Crouzon, Pfeiffer, Apert, Jackson-Weiss, Beare-Stevenson cutis gyrata, and Antley-Bixler syndromes, and Kleeblaatschadel (cloverleaf skull) deformity. The mutations identified to date are concentrated in the previously characterized region of FGFR2 that codes for the extracellular IgIII domain of the receptor protein. The search for mutations in other regions of the gene, however, has been hindered by lack of knowledge of the genomic structure. Using a combination of genomic library screening, long-range PCR, and genomic walking, we have characterized the genomic structure of nearly the entire human FGFR2 gene, including a delineation of the organization and size of all introns and exons and determination of the DNA sequences at the intron/exon boundaries. Comparative analysis of the human FGFR gene family reveals that the genomic organization of the FGFRs is relatively conserved. Moreover, alignment of the amino acid sequences shows that the four corresponding proteins share 46% identity overall, with up to 70% identity between individual pairs of FGFR proteins. However, the FGFR2 gene contains an additional exon not found in other members of the family, and it also has much larger intronic sequences throughout the gene. Remarkable similarities in genomic organization, intron/exon boundaries, and intron sizes are found between the human and mouse FGFR2 genes. Knowledge gained from this study of the human FGFR2 gene structure may prove useful in future screening studies designed to find additional mutations associated with craniosynostotic syndromes, and in understanding the molecular and cell biology of this receptor family.
Assuntos
Receptores Proteína Tirosina Quinases/genética , Receptores de Fatores de Crescimento de Fibroblastos/genética , Processamento Alternativo/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Mapeamento Cromossômico , Clonagem Molecular , Anormalidades Craniofaciais/genética , Éxons/genética , Humanos , Íntrons/genética , Camundongos , Dados de Sequência Molecular , Mutação , Receptores Proteína Tirosina Quinases/química , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Receptores de Fatores de Crescimento de Fibroblastos/química , Alinhamento de SequênciaRESUMO
OBJECTIVES/HYPOTHESIS: Bacteriologic studies of otitis media with effusion (OME) using highly sensitive techniques of molecular biology such as the polymerase chain reaction have demonstrated that traditional culturing methods are inadequate to detect many viable bacteria present in OME. The presence of pathogens attached to the middle-ear mucosa as a bacterial biofilm, rather than as free-floating organisms in a middle-ear effusion, has previously been suggested to explain these observations. The suggestion has been speculative, however, because no visual evidence of such biofilms on middle-ear mucosa has heretofore been collected. The hypotheses motivating the current study were: 1) biofilms of nontypable Hemophilus influenzae will form on the middle-ear mucosa of chinchillas in an experimental model of OME, 2) these biofilms will exhibit changes in density or structure over time, and 3) biofilms are also present on tympanostomy tubes in children with refractory post-tympanostomy otorrhea. The objective of this study was to collect visual evidence of the formation of bacterial biofilms in these situations. STUDY DESIGN: Laboratory study of bacteriology in an animal model and on medical devices removed from pediatric patients. METHODS: Experimental otitis media was induced in chinchillas by transbullar injection of nontypable H. influenzae. Animals were killed in a time series and the surface of the middle-ear mucosa was examined by scanning electron microscopy (SEM) for the presence of bacterial biofilms. Adult and fetal chinchilla uninfected controls were similarly examined for comparison. In addition, tympanostomy tubes that had been placed in children's ears to treat OME and removed after onset of refractory otorrhea or other problems were examined by SEM and by confocal scanning laser microscopy for bacterial biofilms, and compared with unused control tubes. RESULTS: Bacterial biofilms were visually detected by SEM on the middle-ear mucosa of multiple chinchillas in which H. influenzae otitis media had been induced. Qualitative evaluation indicated that the density and thickness of the biofilm might increase until at least 96 hours after injection. The appearance of the middle-ear mucosa of experimental animals contrasted with that of uninjected control animals. Robust bacterial biofilms were also visually detected on tympanostomy tubes removed from children's ears for clinical reasons, in contrast with unused control tubes. CONCLUSIONS: Bacterial biofilms form on the middle-ear mucosa of chinchillas in experimentally induced H. influenzae otitis media and can form on tympanostomy tubes placed in children's ears. Such biofilms can be directly observed by microscopy. These results reinforce the hypothesis that the bacterial aggregates called biofilms, resistant to treatment by antibiotics and to detection by standard culture techniques, may play a major etiologic role in OME and in one of its frequent complications, post-tympanostomy otorrhea.
Assuntos
Biofilmes , Orelha Média/patologia , Infecções por Haemophilus/patologia , Haemophilus influenzae , Otite Média com Derrame/patologia , Animais , Biofilmes/crescimento & desenvolvimento , Chinchila , Microscopia Eletrônica de Varredura , Mucosa/patologiaRESUMO
The transoral approach to pathology of the upper cervical spine is logical, but it is seldom used due to concerns about exposure and infection. The authors report on 16 consecutive patients requiring exposure from clivus through C3 for pathology, including spinal cord compression by rheumatoid pannus, craniovertebral anomalies, and tumor. Exposure was obtained using a Dingman mouth gag and soft palate retraction with silicone rubber sheeting. A horizontal "H" incision was made in the posterior pharyngeal wall creating three layers, closed separately, with attention to a watertight closure of the final mucosal layer. In no case was it necessary to divide the mandible, tongue, soft palate, or uvula. There were no deaths, wound breakdowns, infections, or persistent cerebrospinal fluid leakage. Patients with neurological indications improved postoperatively, and all tumors were grossly resected. Combined otolaryngology/neurosurgical exposure and treatment of pathology involving the upper cervical spine via the transoral approach is safe and effective. Functional results have been excellent, and no major complications were encountered.
Assuntos
Vértebras Cervicais/cirurgia , Adolescente , Adulto , Idoso , Criança , Feminino , Seguimentos , Humanos , Masculino , Métodos , Pessoa de Meia-Idade , Boca , Complicações Pós-OperatóriasRESUMO
Current techniques of laryngotracheal reconstruction require a choice between prolonged stenting (conventional technique) or short-term stenting with maintenance of sedation and paralysis until the airway has stabilized (single-stage laryngotracheal reconstruction). An alternative method is proposed using microplates to provide immediate airway stabilization without stenting. This study was designed to evaluate the long-term effects of microplate repair of stenosis of the subglottis and trachea on the growing larynx. Subglottic stenosis was produced in piglets using a transoral endoscopic technique. Eight animals underwent repair of the stenosis using an anterior cricoid split with microplate distraction and stabilization of the cricoid cartilage and first tracheal ring. The distraction was maintained and airway growth continued for the duration of this study. However, with growth of the larynx the plates migrated away from their original position. In 50% of the animals followed up for 90 days the plates migrated into the airway lumen. This study suggests that rigid distraction of the stenotic airway with microplates is a viable alternative to more traditional methods of repair. However, plate removal at some interval after surgery is required in the growing larynx in order to prevent migration of the plate into the airway.
Assuntos
Laringoestenose/cirurgia , Próteses e Implantes , Animais , Animais Recém-Nascidos , Laringoestenose/patologia , SuínosRESUMO
Children with recurrent respiratory papillomatosis vary greatly in their clinical disease course. Many have mild disease with eventual remission while others present with an early aggressive airway obstructive course. This study consisted of 24 pediatric patients whose specimens underwent polymerase chain reaction analysis for cytomegalovirus (CMV), herpes simplex virus (HSV), and human papillomavirus (HPV) type. Nineteen of 24 specimens contained enough DNA for this study. None of the specimens were found to contain DNA from HPV-16, -18, -31, -33; CMV; or HSV, which contrasts with our previous findings in adults. Ten patients were infected by HPV-11 and seven of these underwent tracheotomy because of an aggressive tumorigenic clinical course. Nine patients were infected by HPV-6 alone of whom only two required a tracheotomy (P = 0.05, Fisher's Exact Test). The early airway obstructive course associated with HPV-11, however, had no bearing on achieving eventual disease remission, with decannulation achieved in eight of nine children.
Assuntos
Neoplasias Brônquicas/virologia , Neoplasias Laríngeas/virologia , Papiloma/virologia , Papillomaviridae , Infecções por Papillomavirus/diagnóstico , Neoplasias da Traqueia/virologia , Infecções Tumorais por Vírus/diagnóstico , Adulto , Obstrução das Vias Respiratórias/etiologia , Neoplasias Brônquicas/diagnóstico , Criança , Pré-Escolar , Cocarcinogênese , Citomegalovirus/genética , Infecções por Citomegalovirus/diagnóstico , DNA Viral/genética , Herpes Simples/diagnóstico , Humanos , Lactente , Neoplasias Laríngeas/diagnóstico , Recidiva Local de Neoplasia/virologia , Regressão Neoplásica Espontânea , Papiloma/diagnóstico , Papillomaviridae/classificação , Papillomaviridae/genética , Reação em Cadeia da Polimerase , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Sorotipagem , Simplexvirus/genética , Neoplasias da Traqueia/diagnóstico , TraqueotomiaRESUMO
OBJECTIVE: To measure the impact of tonsillectomy and adenoidectomy (T&A) on children's behavioral and emotional problems using a standardized assessment. DESIGN: Prospective study. SETTING: Tertiary care children's hospital. PATIENTS: Thirty-six children, aged 2 through 18 years, with symptoms of nighttime snoring, observed apneas, and daytime mouth breathing and physical examination results demonstrating 3+ or 4+ tonsils scheduled for T&A. INTERVENTION: Parents completed a standard survey of their children's symptoms of sleep apnea and a standardized measure of children's competencies and problems, the Child Behavior Checklist for ages 2 through 3 years or 4 through 18 years, before T&A and 3 months postoperatively. MAIN OUTCOME MEASURE: The Child Behavior Checklist total problem score. RESULTS: The preoperative Child Behavior Checklist total problem score was consistent with abnormal behavior for 10 children (28%). After T&A (n = 15), only 2 scores were abnormal, but the change was not statistically significant. In contrast, the mean total problem score was 7.5 points lower after surgery (95% confidence interval, 5.1-9.7), indicating a significant decrease (P<.001, matched t test). CONCLUSIONS: This pilot study demonstrates a high prevalence (28%) of abnormal behavior in children undergoing T&A for chronic upper airway obstruction. Scores on a standardized measure of behavior improve following T&A, but larger studies with increased statistical power are needed to clarify the degree of improvement and its clinical importance.
Assuntos
Adenoidectomia/psicologia , Transtornos do Comportamento Infantil/epidemiologia , Comportamento Infantil , Síndromes da Apneia do Sono/cirurgia , Tonsilectomia/psicologia , Transtornos do Comportamento Infantil/diagnóstico , Transtornos do Comportamento Infantil/etiologia , Pré-Escolar , Feminino , Humanos , Masculino , Projetos Piloto , Período Pós-Operatório , Prevalência , Estudos Prospectivos , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/psicologia , Inquéritos e QuestionáriosRESUMO
Munchausen syndrome by proxy (MSBP) is a form of child abuse in which a parent or caretaker produces or simulates illness in a child. Often great lengths are undertaken to diagnose and treat the myriad of symptoms and problems in these children. Unnecessary examinations, treatments, and hospitalizations ensure. Unfortunately, some victims of this syndrome die. Munchausen syndrome by proxy is a form of child abuse and should be reported appropriately. The diagnosis of MSBP is difficult to make and must be done with caution as the implications for those involved are serious. Therefore, care must be taken in properly identifying cases. We present a case of MSBP complicating the postoperative course of a boy after undergoing ear surgery for cholesteatoma. Characteristics and potential clues to the diagnosis of MSBP are discussed. The goal of our article is to inform otolaryngologists of this syndrome so they may develop a high index of suspicion to better detect its occurrence.
Assuntos
Colesteatoma da Orelha Média/cirurgia , Síndrome de Munchausen Causada por Terceiro/diagnóstico , Complicações Pós-Operatórias , Pré-Escolar , Colesteatoma da Orelha Média/complicações , Colesteatoma da Orelha Média/psicologia , Humanos , Masculino , Complicações Pós-Operatórias/psicologiaRESUMO
OBJECTIVE: To review the effectiveness of a perioperative management protocol and our experience with a large population of patients with von Willebrand disease (vWD) who require adenotonsillar surgery (T&A). DESIGN: A retrospective review of the medical records of all patients having the diagnosis of vWD who underwent T&A between January 1, 1992, and July 31, 1996. SETTING: A tertiary care, university-based children's hospital. INTERVENTIONS: Patients having a preoperative diagnosis of vWD received a single intravenous dose of desmopressin acetate, 0.3 pg/kg, approximately 20 minutes before the induction of anesthesia. Beginning January 15, 1994, a standard management protocol involving the postoperative administration of fluids and electrolytes was followed. MAIN OUTCOME MEASURES: Operative blood loss and the incidence of postoperative bleeding and of hyponatremia. RESULTS: Of approximately 4800 patients who underwent T&A during the study period, 69 patients had a diagnosis of vWD. All 67 patients identified preoperatively received desmopressin; 2 were identified by postoperative workup as a result of excessive surgical bleeding. Minimal immediate postoperative bleeding was noted in 7 patients (10%), but none required intervention. Delayed bleeding occurred in 9 patients (13%); all were readmitted to the hospital for observation, 4 (6%) requiring operative cauterization. Substantial postoperative hyponatremia occurred in 3 patients, and 1 patient had seizure activity. Symptomatic hyponatremia has been avoided since a protocol of fluid and electrolyte administration was instituted. CONCLUSIONS: Although T&A can be performed safely in patients with vWD, it is not without an increased risk of postoperative hemorrhage. The administration of desmopressin has been reported to reduce the risk of bleeding, but it is not without risk. A protocol for fluid and electrolyte management is recommended.
Assuntos
Adenoidectomia , Desamino Arginina Vasopressina/uso terapêutico , Hemostáticos/uso terapêutico , Hemorragia Pós-Operatória/prevenção & controle , Tonsilectomia , Tonsilite/complicações , Tonsilite/cirurgia , Doenças de von Willebrand/complicações , Tonsila Faríngea , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Doenças Linfáticas/complicações , Doenças Linfáticas/cirurgia , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: To compare the postoperative course and complications after tonsillectomy or tonsillectomy and adenoidectomy in children with Down syndrome (group 1) with the postoperative course and complications in children in a control group (group 2). DESIGN: Retrospective review of medical records for the period January 1, 1986, through March 30, 1996. SETTING: Tertiary care children's hospital. PATIENTS: The study included 87 children in group 1 and 64 children in group 2 matched for age, sex, and year of surgery. INTERVENTION: Tonsillectomy and adenoidectomy (group 1, 79 children; group 2, 57 children) and tonsillectomy (group 1, 8 children; group 2, 7 children). MAIN OUTCOME MEASURES: Length of hospitalization and postoperative complications. RESULTS: The length of hospitalization was significantly increased for the children in group 1 compared with that of children in group 2 (1.6 vs 0.80 days; P=.001, Mann-Whitney U test). Twenty-two children (25%) in group 1 required airway management or observation in the pediatric intensive care unit compared with no children in group 2 who required such care (P<.001, Fisher exact test). None of the children in either group required reintubation, continuous positive airway pressure, or tracheotomy. Respiratory complications requiring intervention were 5 times more likely in group 1 (22 [25%] vs 3 [5%]; P<.001, Fisher exact test). The median time until intake of clear liquids and duration of intravenous therapy were significantly increased in group 1 compared with group 2 (5.0 vs 4.0 hours, P=.03; 23.5 vs 16.0 hours, P=.001, respectively; Mann-Whitney U test). CONCLUSIONS: Although tonsillectomy and adenoidectomy can be performed safely in children with Down syndrome, the rate of postoperative respiratory complications is higher and the duration until adequate oral intake is resumed is longer. We therefore recommend that children with Down syndrome be admitted to the hospital overnight after undergoing tonsillectomy and adenoidectomy.
Assuntos
Adenoidectomia , Obstrução das Vias Respiratórias/etiologia , Síndrome de Down , Oxigênio/sangue , Complicações Pós-Operatórias , Tonsilectomia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Síndrome de Down/sangue , Feminino , Humanos , Lactente , Complicações Intraoperatórias , Tempo de Internação/estatística & dados numéricos , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: To reconcile conflicting reports of antibiotic efficacy for otitis media with effusion in children. DATA SOURCES: English-language MEDLINE search ("antibiotics" and "otitis" media with effusion") from January 1980 through December 1990. Current Contents 1990, consultation with experts, and references from review articles, textbook chapters, and retrieved reports. STUDY SELECTION: Randomized clinical trials with concurrent controls (placebo or no drug), and children with at least one ear not violated by tympanocentesis. Ten of the initial 82 articles were selected after blind review of the methods sections. DATA EXTRACTION: We independently evaluated each trial using 20 measures of internal and external validity, then extracted treatment and control responses for an end point of all affected ears free of effusion at the first posttreatment assessment. DATA SYNTHESIS: Pooled analysis of 1325 children yielded a rate difference of 22.8% (95% Cl, 10.5 to 35.1) that was minimally affected by interstudy quality differences, and was unlikely to represent publication bias. Variations in trial outcomes were not attributable to chance, study design, or choice of drug, but were inversely related to the control group natural cure rate. Children with chronic bilateral effusions not related to a recent episode of acute otitis media tended to have lower natural cure rates, and a more favorable response to therapy. CONCLUSIONS: Antibiotics have a clinically and statistically significant impact on the resolution of otitis media with effusion. The association between outcome and natural cure rate has important implications for the design and interpretation of future trials.
Assuntos
Antibacterianos/uso terapêutico , Otite Média com Derrame/tratamento farmacológico , Criança , Humanos , Metanálise como Assunto , Resultado do TratamentoRESUMO
Use of the fiberoptic laser for treatment of tracheobronchial lesions in the adult is well established. However, there is a paucity of experience with the fiberoptic laser in the pediatric airway. Tracheal obstruction caused by granulation tissue or stenosis, as is often seen in children, may be effectively treated with this approach. This article documents the successful use as well as the technologic advantage of the flexible fiberoptic laser systems, primarily the potassium titanyl phosphate (KTP) laser, combined with standard pediatric rigid bronchoscopic equipment in 73 procedures involving 52 children (43 children younger than five years. with an average age of 21 months). Visualization was excellent, assisted or spontaneous ventilation was well maintained, and complications were few.
Assuntos
Broncoscopia/métodos , Terapia a Laser/métodos , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Tecnologia de Fibra Óptica , Humanos , Lactente , Neoplasias Laríngeas/cirurgia , Laringe/cirurgia , Transplante de Pulmão , Papiloma/cirurgia , Traqueia/cirurgia , Estenose Traqueal/cirurgiaRESUMO
Pathologic material and the records of 29 patients with laryngeal papillomatosis were reviewed. The relationship between the type of human papillomavirus (HPV) and the presence of viral coinfections was correlated with clinical outcome. Using polymerase chain reaction, paraffin-embedded specimens were analyzed for the presence of HPV, Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV). The HPV type could be identified in 24 patients' specimens. Twenty-one patients were infected with HPV type 6. The other 3 were infected with HPV type 11 or 16. Three patients developed squamous cell carcinoma, of whom 2 had HPV type 11 or 16. We found HSV, EBV, and CMV in 50%, 12.5%, and 0% of specimens, respectively. An aggressive clinical course was observed in 17 patients. Evidence of coinfection with other viruses was identified in 11 (65%) of these patients. In contrast, a benign clinical course was observed in 7 patients, of whom 2 (29%) had viral coinfections. We conclude that the HPV type and the presence of viral coinfections may be predictive of an aggressive clinical course.
Assuntos
Citomegalovirus/isolamento & purificação , Herpesvirus Humano 4/isolamento & purificação , Neoplasias Laríngeas/virologia , Laringe/virologia , Papiloma/virologia , Papillomaviridae/isolamento & purificação , Simplexvirus/isolamento & purificação , Adulto , Idade de Início , Idoso , Carcinoma de Células Escamosas/patologia , DNA Viral , Feminino , Humanos , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Laringe/patologia , Masculino , Pessoa de Meia-Idade , Papiloma/patologia , Reação em Cadeia da Polimerase , Estudos Prospectivos , RecidivaRESUMO
This study was designed to determine the persistence of culturable bacteria versus DNA in the presence of a middle ear effusion in a chinchilla model of otitis media. Cohorts of animals were either infected with an ampicillin-resistant Haemophilus influenzae strain or injected with a tripartite inoculum consisting of freeze-thawed Streptococcus pneumoniae; pasteurized Moraxella catarrhalis; and DNA from H influenzae. The H influenzae-infected animals displayed culture positivity and polymerase chain reaction positivity through day 35. In the chinchillas infected with the low-copy number inocula of S pneumoniae, DNA was not detectable after day 1 from the co-inoculated pasteurized M catarrhalis bacteria or the purified H influenzae DNA; however, amplifiable DNA from the live low-copy number bacteria persisted through day 21 even though they were not culture-positive past day 3. These results demonstrate that DNA, and DNA from intact but nonviable bacteria, does not persist in an amplifiable form for more than a day in the presence of an effusion; however, live bacteria, while not culturable, persist in a viable state for weeks.
Assuntos
Bactérias/isolamento & purificação , DNA Bacteriano/análise , Otite Média com Derrame/microbiologia , Reação em Cadeia da Polimerase , Resistência a Ampicilina , Animais , Chinchila , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/genética , Haemophilus influenzae/isolamento & purificação , Moraxella catarrhalis/genética , Moraxella catarrhalis/isolamento & purificação , Infecções por Neisseriaceae/microbiologia , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificaçãoRESUMO
Recent studies using the polymerase chain reaction (PCR) have identified bacterial and viral genomic sequences in culture-negative pediatric middle ear effusions. To evaluate this technique in adults, 19 effusions were analyzed to compare bacterial and viral culture and PCR detection of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and adenovirus. Effusions from 4 subjects positive for human immunodeficiency virus (HIV) were analyzed by PCR for HIV virus. Three of 19 effusions were culture-positive for bacteria, and 0 of 19 for viruses. Fifteen of 19 effusions were PCR-positive for bacterial genomic sequences, and 0 of 19 for adenovirus. Thirteen of 15 PCR-positive specimens demonstrated S pneumoniae, 5 of 15 H influenzae, and 0 of 13 M catarrhalis. All 4 effusions from HIV-positive subjects were PCR-positive for HIV. No effusion was culture-positive and PCR-negative. These results confirm that culture-negative middle ear effusions contain genomic sequences from bacterial pathogens. Finding of HIV RNA and DNA in effusion from HIV-positives suggests replicating virus in this fluid.