RESUMO

PURPOSE: The aim of this study is to describe the variable phenotype of congenital corneal opacities occurring in patients with biallelic CYP1B1 pathogenic variants. METHODS: A retrospective chart review was conducted to identify patients with congenital corneal opacities and CYP1B1 pathogenic variants seen at UPMC Children's Hospital of Pittsburgh. Ophthalmic examination, high-frequency ultrasound, anterior segment optical coherence tomography, histopathologic images, and details of genetic testing were reviewed. RESULTS: Three children were identified. All presented with raised intraocular pressure. Two patients showed bilateral limbus-to-limbus avascular corneal opacification that did not resolve with intraocular pressure control; 1 showed unilateral avascular corneal opacity with a crescent of clear cornea, iridocorneal adhesions, iridolenticular adhesions, and classical features of congenital glaucoma in the fellow eye (enlarged corneal diameter, Haab striae, and clearing of the corneal clouding with appropriate intraocular pressure control). The first 2 patients were visually rehabilitated with penetrating keratoplasty. Histopathology revealed distinct features: a variably keratinized epithelium; a thick but discontinuous Bowman-like layer with areas of disruption and abnormal cellularity; Descemet membrane, when observed, showed reduced endothelial cells; and no pathological changes of Haab striae were identified. Two patients had compound heterozygous pathogenic variants in CYP1B1 causing premature stop codons, whereas 1 was homozygous for a pathogenic missense variant. CONCLUSIONS: Congenital corneal opacities seen in biallelic CYP1B1 pathogenic variants have a variable phenotype. One is that commonly termed as Peters anomaly type 1 (with iridocorneal adhesions, with or without iridolenticular adhesions) and the other is a limbus-to-limbus opacity, termed CYP1B1 cytopathy. Clinicians should be aware of this phenotypic variability.

Assuntos

Doenças da Córnea , Opacidade da Córnea , Criança , Humanos , Estudos Retrospectivos , Células Endoteliais , Opacidade da Córnea/diagnóstico , Opacidade da Córnea/genética , Opacidade da Córnea/cirurgia , Doenças da Córnea/diagnóstico , Doenças da Córnea/genética , Fenótipo , Variação Biológica da População , Citocromo P-450 CYP1B1/genética

RESUMO

OBJECTIVE: To describe preschool neurodevelopmental outcomes of children with complex congenital heart disease (CHD), who were evaluated as part of a longitudinal cardiac neurodevelopmental follow-up program, as recommended by the American Heart Association and the American Academy of Pediatrics, and identify predictors of neurodevelopmental outcomes in these children. STUDY DESIGN: Children with CHD meeting the American Heart Association/American Academy of Pediatrics high-risk criteria for neurodevelopmental delay were evaluated at 4-5 years of age. Testing included standardized neuropsychological measures. Parents completed measures of child functioning. Scores were compared by group (single ventricle [1V]; 2 ventricles [2V]; CHD plus known genetic condition) to test norms and classified as: normal (within 1 SD of mean); at risk (1-2 SD from mean); and impaired (>2 SD from mean). RESULTS: Data on 102 patients were analyzed. Neurodevelopmental scores did not differ based on cardiac anatomy (1V vs 2V); both groups scored lower than norms on fine motor and adaptive behavior skills, but were within 1 SD of norms. Patients with genetic conditions scored significantly worse than 1V and 2V groups and test norms on most measures. CONCLUSIONS: Children with CHD and genetic conditions are at greatest neurodevelopmental risk. Deficits in children with CHD without genetic conditions were mild and may not be detected without formal longitudinal testing. Parents and providers need additional education regarding the importance of developmental follow-up for children with CHD.

Assuntos

Deficiências do Desenvolvimento/etiologia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Deficiência Intelectual/etiologia , Fatores Etários , Pré-Escolar , Estudos de Coortes , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/epidemiologia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/epidemiologia , Modelos Logísticos , Estudos Longitudinais , Masculino , Análise Multivariada , Testes Neuropsicológicos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Estados Unidos/epidemiologia

RESUMO

This article discusses current ethical issues associated with childbirth in the United States. It provides a review of moral problems and ethical choices made by parents and health-care professionals during the prenatal, intrapartum, and postpartum periods...

Assuntos

Feminino , Humanos , Lactente , Bioética , Parto , Ética Profissional , Cuidado Pré-Natal

RESUMO

OBJECTIVES: To compare proportions of infants at different gestational ages discharged from the neonatal intensive care unit (NICU) on home oxygen, to determine how many were classified with chronic lung disease based on timing of discharge on home oxygen, and to determine the percentage discharged on home oxygen who received mechanical ventilation. STUDY DESIGN: We evaluated a retrospective cohort of infants of 23-43 weeks' gestational age discharged from 228 NICUs in 2009, using the Pediatrix Clinical Data Warehouse. Multilevel logistic regression analysis identified predictors of home oxygen use among extremely preterm, early-moderate preterm, late preterm, and term infants. Duration of mechanical ventilation and median length of stay were calculated for infants discharged on home oxygen. RESULTS: For the 48877 infants studied, the rate of home oxygen use ranged from 28% (722 of 2621) in extremely preterm infants to 0.7% (246 of 34 934) in late preterm and term infants. Extremely preterm infants composed 56% (722 of 1286) of the infants discharged on home oxygen; late preterm and term infants, 19% (246 of 1286). After gestational age, mechanical ventilation was the main predictor of home oxygen use; however, 61% of the late preterm and term infants discharged on home oxygen did not receive ventilation. The median length of hospital stay was 95 days (IQR, 76-114 days) for extremely preterm infants discharged on home oxygen, but only 15 days (IQR, 10-22 days) for late preterm and term ventilated infants discharged on home oxygen. CONCLUSION: Although home oxygen use is uncommon in later-gestation infants, the greater overall numbers of later-gestation infants contribute significantly to the increased need for home oxygen for infants at NICU discharge. Neither respiratory failure nor lengthy hospitalization is a prerequisite for home oxygen use at later gestational age.

Assuntos

Assistência Domiciliar , Oxigênio/uso terapêutico , Doença Crônica/terapia , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/terapia , Terapia Intensiva Neonatal , Tempo de Internação , Modelos Logísticos , Pneumopatias/terapia , Masculino , Alta do Paciente , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo

RESUMO

Chronic hyponatremia, unless associated with extracellular fluid volume expansion, is an infrequent electrolyte imbalance in pediatrics. We report an infant with chronic hyponatremia suggestive of a syndrome of inappropriate secretion of antidiuretic hormone (SIADH), in the absence of ADH secretion. A mutation was found in the same codon of the gene that results in a loss-of- function of arginine vasopressin receptor 2 (AVPR2) observed in congenital nephrogenic diabetes insipidus. In this case, a gain-of- function of AVPR 2 was found to be responsible for a SIADH-like state.

Assuntos

Hiponatremia/genética , Mutação , Receptores de Vasopressinas/genética , Doença Crônica , Diagnóstico Diferencial , Líquido Extracelular/metabolismo , Humanos , Hiponatremia/diagnóstico , Hiponatremia/metabolismo , Hiponatremia/terapia , Síndrome de Secreção Inadequada de HAD/diagnóstico , Lactente , Masculino , Sódio/metabolismo

RESUMO

OBJECTIVES: To investigate the effect of esophageal mechanosensitive and chemosensitive stimulation on the magnitude and recruitment of peristaltic reflexes and upper esophageal sphincter (UES)-contractile reflex in premature infants. STUDY DESIGN: Esophageal manometry and provocation testing were performed in the same 18 neonates at 33 and 36 weeks postmenstrual age (PMA). Mechanoreceptor and chemoreceptor stimulation were performed using graded volumes of air, water, and apple juice (pH 3.7), respectively. The frequency and magnitude of the resulting esophago-deglutition response (EDR) or secondary peristalsis (SP), and esophago-UES-contractile reflex (EUCR) were quantified. RESULTS: Threshold volumes to evoke EDR, SP, or EUCR were similar. The recruitment and magnitude of SP and EUCR increased with volume increments of air and water in either study (P < .05). However, apple juice infusions resulted in increased recruitment of EDR in the 33 weeks group (P < .05), and SP in the 36 weeks group (P < .05). The magnitude of EUCR was also volume responsive (all media, P < .05), and significant differences between media were noted (P < .05). At maximal stimulation (1 mL, all media), sensory-motor characteristics of peristaltic and EUCR reflexes were different (P < .05) between media and groups. CONCLUSIONS: Mechano- and chemosensitive stimuli evoke volume-dependent specific peristaltic and UES reflexes at 33 and 36 weeks PMA. The recruitment and magnitude of these reflexes are dependent on the physicochemical properties of the stimuli in healthy premature infants.

Assuntos

Células Quimiorreceptoras/fisiologia , Esôfago/fisiologia , Mecanorreceptores/fisiologia , Reflexo/fisiologia , Ar , Bebidas , Deglutição/fisiologia , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Manometria , Contração Muscular/fisiologia , Perfusão , Peristaltismo/fisiologia , Recrutamento Neurofisiológico , Limiar Sensorial/fisiologia , Água

RESUMO

An ongoing sero-epidemiological study of the Terena reservation of Limao Verde, known to have a high prevalence and incidence of FS, has revealed important information about this autoimmune disease. During surveillance of this population of approximately 1,200, which began in 1994, we documented 43 FS cases and studied the transition from the normal state to the disease state in several of these individuals. Furthermore, we established that FS patients as well as a large number of normal individuals on the reservation possess anti-dsg1 autoantibodies. The following interesting observations were made: (1) the ectodomain of dsg1 contains epitopes recognized by both autoantibodies and T cells from FS patients; (2) pathogenic anti-dsg1 autoantibodies in FS belong to the IgG4 subclass; (3) nonpathogenic anti-dsg1 autoantibodies of the IgG1 subclass were detected in normal individuals from Limao Verde and in patients in the preclinical stage of the disease; (4) anti-dsg1 autoantibodies from normal individuals and patients in the preclinical stage of FS recognize the EC5 domain of dsg1, whereas pathogenic anti-dsg1 autoantibodies bind the EC1/EC2 domains; (5) houses of FS patients are rustic, with thatched roofs and walls and dirt floors; (6) there was a high frequency of hematophagous insects (bedbugs and kissing bugs) in the houses of FS patients; (7) previous studies revealed that the predominant black fly on this reservation belongs to the species Simunlium nigrimanum. These findings suggest that the environmental antigen(s) triggering the autoimmune response in FS may be linked to exposure to hematophagous insects.

Assuntos

Exposição Ambiental , Indígenas Sul-Americanos , Pênfigo/etnologia , Pênfigo/imunologia , Brasil/epidemiologia , Doenças Endêmicas , Humanos , Fatores de Risco

RESUMO

OBJECTIVE: To define epidemiologic and clinical characteristics of newly diagnosed pediatric inflammatory bowel disease (IBD) in a large population-based model. STUDY DESIGN: All pediatric gastroenterologists providing care for Wisconsin children voluntarily identified all new cases of IBD during a 2-year period. Demographic and clinical data were sent to a central registry prospectively for analysis. RESULTS: The incidence of IBD in Wisconsin children was 7.05 per 100,000, whereas the incidence for Crohn's disease was 4.56, more than twice the rate of ulcerative colitis (2.14). An equal IBD incidence occurred among all ethnic groups, and children from sparsely and densely populated counties were equally affected. The majority (89%) of new IBD diagnoses were nonfamilial. CONCLUSIONS: This study provides novel, prospective, and comprehensive information on pediatric IBD incidence within the United States. The surprisingly high incidence of pediatric IBD, the predominance of Crohn's disease over ulcerative colitis, the low frequency of patients with a family history, the equal distribution of IBD among all racial and ethnic groups, and the lack of a modulatory effect of urbanization on IBD incidence collectively suggest that the clinical spectrum of IBD is still evolving and point to environmental factors contributing to the pathogenesis.

Assuntos

Doenças Inflamatórias Intestinais/epidemiologia , Adolescente , Criança , Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Endoscopia Gastrointestinal , Feminino , Humanos , Incidência , Doenças Inflamatórias Intestinais/diagnóstico , Masculino , Estudos Prospectivos , Wisconsin/epidemiologia

RESUMO

OBJECTIVES: We studied the maturation of esophageal body and upper esophageal sphincter (UES) motor responses that protect against reflux in newborns. STUDY DESIGN: The responses of esophageal body and UES on midesophageal provocation were quantified using a micromanometric water perfusion system and a specially designed catheter with a UES sleeve and 5 side-hole recording sites. Eighteen healthy premature infants were studied twice, at 33.4 weeks' and 35.7 weeks' mean postmenstrual ages (PMAs). RESULTS: Mean threshold volumes and the distribution of responses including secondary peristalsis, UES pressure increase, and primary peristalsis were similar for air and liquids. Secondary peristalsis and UES pressure increases were volume dependent for both studies, but their characteristics changed as PMA increased in that (1) completely propagated secondary peristalsis with liquids increased; (2) proximal esophageal contraction duration was shorter for air and liquids; and (3) propagating velocity for liquids was faster. CONCLUSIONS: Esophageal and UES motor responses to abrupt midesophageal provocation are present as early as 33 weeks' PMA, and the response-characteristics improve during development. Reflexes that may facilitate esophageal clearance include (1) secondary peristalsis; (2) esophago-UES-contractile reflex; and (3) esophago-deglutition response.

Assuntos

Transtornos da Motilidade Esofágica/diagnóstico , Transtornos da Motilidade Esofágica/fisiopatologia , Esôfago/fisiopatologia , Transtornos de Deglutição/etiologia , Limiar Diferencial/fisiologia , Eletromiografia/instrumentação , Transtornos da Motilidade Esofágica/complicações , Feminino , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/fisiopatologia , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Manometria/instrumentação , Músculo Liso/fisiopatologia , Índice de Gravidade de Doença

RESUMO

Background - Pemphigus foliaceus is an autoimmune skin disease mediated by autoantibodies against desmoglein 1. The endemic form is thought to ahve an environmental cause. The Terena reservation of Limao Verde in Mato Grosso do Sul, Brazil, is a recently identifies focus of the disease, with a prevalence of 3.4 percent in the population. We tested the hypothesis taht normal subjects living in an endemic area have antibodies agaisnt desmoglein 1. Methods - We used an enzyme-linked immunosorbent assay to defect antibodies agaisnt desmoglein 1 in serum samples from 60 patients with endemic pemphigus foliaceus (fogo selvagem) who lived in Limao Verde or elsewhere in Brazil, 372 normal subjects (without pemphigus foliaceus) from Limao Verde and surrounding location, and 126 normal subjects from the United States and Japan. Results - Antibodies against desmoglein 1 were detected in 59 of the 60 patients with fogo selvagem (98 percent) but in only 3 of the 126 normal subjects from the United States and Japan (2 percent). Antibodies were also detected in 51 of the 93 normal subjects from Limao Verde (55 percent) and in 54 of the 279 normal subjects from surrounding areas (19 percent). Serum samples obtained one to four years before the onset of disease were available for five patients; all five had antibodies in the initial serum serumsamples, and the onset of disease was associated with a marked increase in antibody values. Conclusions - The prevalence of antibodies against desmoglein 1 is high among normal subjects living in an area where fogo selvagem is endemic, and the onset of the disease is preceded by a sustained antibody response. These findings support the concept that the production of antibodies against desmoglein 1 is initiated by exporure to an unknown environmental agent

Assuntos

Humanos , Desmogleína 1/química , Desmogleína 1/uso terapêutico , Pênfigo/diagnóstico , Pênfigo/fisiopatologia , Pênfigo/microbiologia , Pênfigo/prevenção & controle