RESUMEN
The rate of caesarean section delivery (CSD) is increasing worldwide. It remains unclear whether disruption of mother-to-neonate transmission of microbiota through CSD occurs and whether it affects human physiology. Here we perform metagenomic analysis of earliest gut microbial community structures and functions. We identify differences in encoded functions between microbiomes of vaginally delivered (VD) and CSD neonates. Several functional pathways are over-represented in VD neonates, including lipopolysaccharide (LPS) biosynthesis. We link these enriched functions to individual-specific strains, which are transmitted from mothers to neonates in case of VD. The stimulation of primary human immune cells with LPS isolated from early stool samples of VD neonates results in higher levels of tumour necrosis factor (TNF-α) and interleukin 18 (IL-18). Accordingly, the observed levels of TNF-α and IL-18 in neonatal blood plasma are higher after VD. Taken together, our results support that CSD disrupts mother-to-neonate transmission of specific microbial strains, linked functional repertoires and immune-stimulatory potential during a critical window for neonatal immune system priming.
Asunto(s)
Microbioma Gastrointestinal/fisiología , Cesárea , Parto Obstétrico , Femenino , Microbioma Gastrointestinal/genética , Humanos , Técnicas In Vitro , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Interleucina-18/metabolismo , Lipopolisacáridos/metabolismo , Metagenómica/métodos , Embarazo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: We give the first account of failure of extracorporeal membrane oxygenation therapy secondary to congenital cystic malformation of the lung (CCAM) type 0. DESIGN: Case report. SETTING: Pediatric intensive care unit. PATIENT: A female neonate, appropriate for gestational age, with respiratory failure immediately after delivery. INTERVENTIONS: : Cardiopulmonary support with venoarterial extracorporeal membrane oxygenation. RESULTS: There was no improvement of pulmonary function, and the patient died. CCAM type 0 was diagnosed postmortem. CONCLUSIONS: CCAM type 0 should be considered as a rare differential diagnosis of irreversible lung pathologies leading to failure of extracorporeal membrane oxygenation therapy for neonatal respiratory failure.
Asunto(s)
Malformación Adenomatoide Quística Congénita del Pulmón/diagnóstico , Insuficiencia Respiratoria/genética , Oxigenación por Membrana Extracorpórea , Resultado Fatal , Femenino , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Pulmón/anomalías , Pulmón/patología , Pronóstico , Insuficiencia Respiratoria/terapia , Insuficiencia del TratamientoRESUMEN
Perturbations to the colonization process of the human gastrointestinal tract have been suggested to result in adverse health effects later in life. Although much research has been performed on bacterial colonization and succession, much less is known about the other two domains of life, archaea, and eukaryotes. Here we describe colonization and succession by bacteria, archaea and microeukaryotes during the first year of life (samples collected around days 1, 3, 5, 28, 150, and 365) within the gastrointestinal tract of infants delivered either vaginally or by cesarean section and using a combination of quantitative real-time PCR as well as 16S and 18S rRNA gene amplicon sequencing. Sequences from organisms belonging to all three domains of life were detectable in all of the collected meconium samples. The microeukaryotic community composition fluctuated strongly over time and early diversification was delayed in infants receiving formula milk. Cesarean section-delivered (CSD) infants experienced a delay in colonization and succession, which was observed for all three domains of life. Shifts in prokaryotic succession in CSD infants compared to vaginally delivered (VD) infants were apparent as early as days 3 and 5, which were characterized by increased relative abundances of the genera Streptococcus and Staphylococcus, and a decrease in relative abundance for the genera Bifidobacterium and Bacteroides. Generally, a depletion in Bacteroidetes was detected as early as day 5 postpartum in CSD infants, causing a significantly increased Firmicutes/Bacteroidetes ratio between days 5 and 150 when compared to VD infants. Although the delivery mode appeared to have the strongest influence on differences between the infants, other factors such as a younger gestational age or maternal antibiotics intake likely contributed to the observed patterns as well. Our findings complement previous observations of a delay in colonization and succession of CSD infants, which affects not only bacteria but also archaea and microeukaryotes. This further highlights the need for resolving bacterial, archaeal, and microeukaryotic dynamics in future longitudinal studies of microbial colonization and succession within the neonatal gastrointestinal tract.
RESUMEN
Autoimmune enteric leiomyositis is an extraordinary rare cause of acquired chronic intestinal pseudo-obstruction in children. We report a 5-year-old girl who developed chronic intestinal pseudo-obstruction 3 years after an autoimmune hepatitis. Mucosal biopsies of the upper gastrointestinal tract and colon showed minimal inflammatory changes. On full-thickness biopsies of the small intestine, a dense lymphocytic infiltrate of the muscularis propria was seen, mainly consisting of cytotoxic T lymphocytes. Smooth muscle fibers were degenerated and diminished, but the myenteric plexus was intact. The coexistence of an autoimmune hepatitis in our case indicates an expansion of autoreactive T cells to homologous self-antigens. It is of practical importance for histopathological diagnosis that inflammation in autoimmune enteric leiomyositis affects the muscularis propria of the small intestine, whereas mucosa and submucosa do not show severe inflammatory changes. Therefore, correct diagnosis may be missed in peroral and peranal mucosal biopsies, but full-thickness biopsies are required.
Asunto(s)
Enfermedades Autoinmunes/complicaciones , Seudoobstrucción Intestinal/etiología , Intestino Delgado/patología , Músculo Liso/patología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Preescolar , Diagnóstico Diferencial , Femenino , Hepatitis/complicaciones , Hepatitis/inmunología , Humanos , Inmunohistoquímica , Lactante , Mucosa Intestinal/inmunología , Mucosa Intestinal/patología , Seudoobstrucción Intestinal/inmunología , Seudoobstrucción Intestinal/patología , Intestino Delgado/inmunología , Músculo Liso/inmunologíaRESUMEN
Congenital generalized lipodystrophy (CGL) is characterized by the absence of adipose tissue from birth due to a hypothetical differentiation block. The genetic causes of CGL are still not completely understood. Subepidermal, fibroblast-like cells were prepared from the sc tissue of an infant with CGL. Preadipocytes from sc adipose tissue and foreskin fibroblasts from three healthy patients, respectively, were used as controls. Adipose differentiation was induced in cultured cells by exposure to 10 nM insulin, 200 pM T(3), 1 microM cortisol, and 2 microM rosiglitazone. Under these conditions 42% of the subepidermal, fibroblast-like CGL cells developed into mature adipocytes. Adipogenic differentiation was dependent on rosiglitazone. The differentiation rate was comparable in cultures of preadipocytes from control patients maintained under the same conditions (53%, 38%, and 20%). In contrast, foreskin fibroblasts did not differentiate into adipocytes. Morphological changes in CGL cells during differentiation were associated with the expression of fat cell-specific mRNAs (PPARgamma, leptin, and glut-4). In addition, these cells revealed characteristic features of mature adipocytes, such as lipogenesis or leptin secretion. Taken together, we show that adipocyte precursor cells were present in subepidermal tissue of a patient with CGL and were able to differentiate into adipocytes in the presence of a thiazolidinedione. These findings strongly support clinical trials with thiazolidinediones in patients with CGL.
Asunto(s)
Adipocitos/patología , Epidermis/patología , Fibroblastos/patología , Lipodistrofia/congénito , Lipodistrofia/patología , Tiazoles/farmacología , Tiazolidinedionas , Adipocitos/fisiología , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Expresión Génica , Humanos , Recién Nacido , Leptina/biosíntesis , Lípidos/biosíntesis , Lipodistrofia/genética , Masculino , Rosiglitazona , Células Madre/patologíaRESUMEN
Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near complete absence of adipose tissue from birth. Recently, mutations in 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) and Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) genes were reported in pedigrees linked to chromosomes 9q34 and 11q13, respectively. There are limited data regarding phenotypic differences between the various subtypes of CGL. Furthermore, whether there are additional loci for CGL remains unknown. Therefore, we genotyped 45 pedigrees with CGL for AGPAT2 and BSCL2 loci and compared the phenotypes in the various subtypes. Twenty-six pedigrees harbored mutations, including seven novel variants, in the AGPAT2 gene, and 11 pedigrees harbored mutations in the BSCL2 gene, including five novel variants. Eight pedigrees had no substantial alterations in either gene. Of these, three informative pedigrees showed no linkage to markers spanning the AGPAT2 and BSCL2 loci, and in six of the affected subjects, the transcripts of AGPAT2 and BSCL2 were normal. All subtypes of CGL showed high prevalence of diabetes, hypertriglyceridemia, and acanthosis nigricans. However, patients with BSCL2 mutations had lower serum leptin levels, an earlier onset of diabetes, and higher prevalence of mild mental retardation compared with other subtypes. We conclude that besides AGPAT2 and BSCL2, there may be additional loci for CGL. The genetic heterogeneity in CGL patients is accompanied by phenotypic heterogeneity.
Asunto(s)
Aciltransferasas/genética , Subunidades gamma de la Proteína de Unión al GTP , Heterogeneidad Genética , Proteínas de Unión al GTP Heterotriméricas/genética , Lipodistrofia/genética , 1-Acilglicerol-3-Fosfato O-Aciltransferasa , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 9 , Análisis Mutacional de ADN , Femenino , Ligamiento Genético , Humanos , Lipodistrofia/congénito , Masculino , Mutación , Linaje , FenotipoRESUMEN
Cantú syndrome consists of hypertrichosis, osteochondrodysplasia, and cardiomegaly, and has been reported in 18 patients to date. We report an infant with Cantú syndrome. In addition to typical findings, he had relatively mild radiological and cardiological manifestations. Previously undescribed findings included pyloric stenosis and elevated alkaline phosphatase levels. Brain scans showed bilateral calcification of the Arteriae thalamostriatae and widening of the outer liquor spaces and lateral ventricles. Because the propositus is the youngest patient reported to date, our findings refine the clinical spectrum of Cantú syndrome in neonates and young infants. The etiology and mode of inheritance of Cantú syndrome are unknown. Most cases are sporadic. Microdeletions have been discussed as a possible cause of Cantú syndrome. Recently, several syndromes with multiple congenital anomalies and mental retardation have been shown to be caused by subtelomeric chromosome aberrations. We excluded the presence of a cryptic subtelomeric chromosome anomaly in our patient by fluorescence in situ hybridization (FISH) screening with locus-specific probes.
Asunto(s)
Anomalías Múltiples/genética , Cardiomegalia/genética , Aberraciones Cromosómicas , Hipertricosis/genética , Osteocondrodisplasias/genética , Anomalías Múltiples/patología , Adulto , Cardiomegalia/diagnóstico , Femenino , Humanos , Hipertricosis/diagnóstico , Hibridación Fluorescente in Situ , Lactante , Discapacidad Intelectual , Cariotipificación , Masculino , Osteocondrodisplasias/diagnóstico , Embarazo , Complicaciones del Embarazo , Síndrome , TelómeroRESUMEN
Male gender predisposes to severe sepsis and septic shock. This effect has been ascribed to higher levels of testosterone. The ESPNIC ARDS database was searched, to determine if there was evidence of a similar male preponderance in severe sepsis in prepubertal patients in spite of low levels of male sex hormones at this age. A total of 72 patients beyond neonatal age up to 8 years of age with sepsis were identified. The male/female (M/F) ratio was 1.7 (1.0;2.7) and differed significantly from non-septic ARDS patients in this age group [n = 209; M/F = 1.0 (0.8;1.3)]. The highest M/F-ratio was observed in the first year of life. The gender-ratio was the same as reported in adult patients with sepsis. In infants between 1 month and 12 months of age, the ratio was 2.8 (1.2;6.1) (Chi2= 5.6; P< 0.01), in children from 1 year to 8 years of age it was 1.2 (0.7;2.2) (n.s.). In a subgroup of patients with severe sepsis or septic shock, caused by other bacteria than Neisseria meningitidis, the M/F-ratio was 2.1 (1.2;3.6) (Chi2= 4.9; P<0.05), while in patients with meningococcal sepsis (n=20) the M/F-ratio was 1.0 (0.4;2.3). In prepubertal ARDS patients with sepsis an increased frequency of male patients is found, comparable to adults. No male preponderance exists in patients with ARDS due to meningococcal septic shock. Since levels of testosterone and other sex hormones are extremely low at this age, we conclude that factors others than testosterone are involved in the male preponderance in severe sepsis.
Asunto(s)
Síndrome de Dificultad Respiratoria/complicaciones , Sepsis/etiología , Niño , Preescolar , Femenino , Hormonas Esteroides Gonadales/sangre , Humanos , Lactante , Masculino , Síndrome de Dificultad Respiratoria/sangre , Síndrome de Dificultad Respiratoria/epidemiología , Sepsis/sangre , Sepsis/epidemiología , Caracteres Sexuales , Distribución por SexoRESUMEN
OBJECTIVE: To determine whether bovine surfactant given in cases of severe pediatric acute respiratory distress syndrome (ARDS) improves oxygenation. DESIGN: Single-center study with 19 patients, followed by a multicenter randomized comparison of surfactant with a standardized treatment algorithm. Primary endpoint PaO(2)/FIO(2) at 48 h, secondary endpoints: PaO(2)/FIO(2) at 2, 4, 12, and 24 h, survival, survival without rescue, days on ventilator, subgroups analyzed by analysis of variance to identify patients who might benefit from surfactant. SETTING: Multicenter study in 19 reference centers for ARDS. PATIENTS: Children after the 44th postconceptional week and under 14 years old, admitted for at least 4 h, ventilated for 12-120 h, and without heart failure or chronic lung disease. In the multicenter study 35 patients were recruited; 20 were randomized to the surfactant group and 15 to the nonsurfactant group. Decreasing recruitment of patients led to a preliminary end of this study. INTERVENTIONS: Administration of 100 mg/kg bovine surfactant intratracheally under continuous ventilation and PEEP, as soon as the PaO(2)/FIO(2) ratio dropped to less than 100 for 2 h (in the pilot study increments of 50 mg/kg as long as the PaO(2)/FIO(2) did not increase by 20%). A second equivalent dose within 48 h was permitted. RESULTS: In the pilot study the PaO(2)/FIO(2) increased by a mean of 100 at 48 h (n=19). A higher PaO(2)/FIO(2) ratio was observed in the surfactant group 2 h after the first dose (58 from baseline vs. 9), at 48 h there was a trend towards a higher ratio (38 from baseline vs. 22). The rate of rescue therapy was significantly lower in the surfactant group. Outcome criteria were not affected by a second surfactant dose (n=11). A significant difference in PaO(2)/FIO(2) in favor of surfactant at 48 h was found in the subgroup with an initial PaO(2)/FIO(2) ratio higher than 65 and in patients without pneumonia. CONCLUSIONS. Surfactant therapy in severe ARDS improves oxygenation immediately after administration. This improvement is sustained only in the subgroup of patients without pneumonia and that with an initial PaO(2)/FIO(2) ratio higher than 65
Asunto(s)
Oxígeno/metabolismo , Surfactantes Pulmonares/uso terapéutico , Síndrome de Dificultad Respiratoria/terapia , Enfermedad Aguda , Adolescente , Algoritmos , Análisis de Varianza , Animales , Bovinos , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Respiración Artificial , Síndrome de Dificultad Respiratoria/fisiopatología , Resultado del TratamientoRESUMEN
A neonate suffering from herpes simplex virus type 2 disease with central nervous system involvement developed an early recurrence under acyclovir therapy. Isolates from the cerebrospinal fluid and skin lesions were acyclovir resistant, while viruses from blood and trachea were not. Acyclovir combined with foscavir followed by long-term suppressive acyclovir therapy supported normal neurological development.
RESUMEN
BACKGROUND: Primary coenzyme Q10 (CoQ10) deficiencies are heterogeneous autosomal recessive disorders. CoQ2 mutations have been identified only rarely in patients. All affected individuals presented with nephrotic syndrome in the first year of life. METHODS: An infant is studied with myoclonic seizures and hypertrophic cardiomyopathy in the first months of life and developed a nephrotic syndrome in a later stage. RESULTS: At three weeks of age, the index patient developed myoclonic seizures. In addition, he had hypertrophic cardiomyopathy and increased CSF lactate. A skeletal muscle biopsy performed at two months of age disclosed normal activities of the oxidative phosphorylation complexes. The child was supplemented with CoQ10 (5 mg/kg/day). At the age of four months, brain MR images showed bilateral increased signal intensities in putamen and cerebral cortex. After that age, he developed massive proteinuria. The daily dose of CoQ10 was increased to 30 mg/kg. Renal biopsy showed focal segmental glomerulosclerosis. Biochemical analyses of a kidney biopsy sample revealed a severely decreased activity of succinate cytochrome c reductase [complex II + III] suggesting ubiquinone depletion. Incorporation of labelled precursors necessary for CoQ10 synthesis was significantly decreased in cultured skin fibroblasts. His condition deteriorated and he died at the age of five months. A novel homozygous mutation c.326G > A (p.Ser109Asn) was found in COQ2. CONCLUSIONS: In contrast to previously reported patients with CoQ2 the proband presented with early myoclonic epilepsy, hypertrophic cardiomyopathy and only in a later stage developed a nephrotic syndrome. The phenotype of this patient enlarges the phenotypical spectrum of the multisystem infantile variant.
Asunto(s)
Transferasas Alquil y Aril/genética , Ataxia/genética , Cardiomiopatía Hipertrófica/genética , Epilepsias Mioclónicas/genética , Enfermedades Mitocondriales/genética , Debilidad Muscular/genética , Mutación/genética , Síndrome Nefrótico/genética , Ubiquinona/deficiencia , Ataxia/complicaciones , Ataxia/patología , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/patología , Imagen de Difusión por Resonancia Magnética , Electroencefalografía , Epilepsias Mioclónicas/complicaciones , Epilepsias Mioclónicas/patología , Pruebas Genéticas , Humanos , Lactante , Riñón/patología , Riñón/ultraestructura , Espectroscopía de Resonancia Magnética , Masculino , Microscopía Electrónica de Transmisión , Enfermedades Mitocondriales/complicaciones , Enfermedades Mitocondriales/patología , Debilidad Muscular/complicaciones , Debilidad Muscular/patología , Músculo Esquelético/patología , Síndrome Nefrótico/etiología , Síndrome Nefrótico/patología , Ubiquinona/genéticaRESUMEN
OBJECTIVE: The objective of this study was to determine the epidemiology of acute respiratory distress syndrome (ARDS) in children and adolescents aged 1 mo to 18 yrs. DESIGN: The authors conducted a population-based prospective multicenter survey from February 1 to 28,1997, June 1 to 30, 2001, and April 1 to 30, 2004. SETTING: This study was conducted at 94 intensive care units (ICUs) in 1997, 92 ICUs in 2001 and 2004 in the district of Cologne, Germany with a population of 4.15 (1997), 4.28 (2001), and 4.35 million (2004), respectively. The survey was not confined to children's hospitals, but addressed all ICUs. PATIENTS: This study consisted of children and adolescents aged 1 mo to 18 yrs. Term neonates and premature babies with a corrected age below 43 gestational weeks were excluded. ARDS was defined according to the consensus criteria (acute-onset pulmonary process of noncardiogenic origin, Pao(2)/FIo(2) ratio <200, bilateral alveolar infiltration in chest radiograph). RESULTS: All ICUs at pediatric hospitals and all but seven adult ICUs collaborated. Incidence of ARDS was assessed as the number of patients entering ARDS criteria within the three study periods divided by the total population in this age group. During the study period, 12 pediatric patients were diagnosed as having ARDS. In five cases, onset was before the study period, representing a calculated prevalence of 5.5 x 10(-5) [3.1 x 10(-5); 9.6 x 10(-5)] cases per year and an incidence of 3. 2 x 10(-5) [1.5 x 10(-5); 6.6 x 10(-5)] cases per year in the age group under investigation. CONCLUSION: This is the first population-based evaluation of the incidence of ARDS in the pediatric age group. It shows that the incidence of ARDS in this age group is low. This makes randomized studies on pediatric ARDS aiming on the end point "outcome" nearly impossible.
Asunto(s)
Cuidados Críticos/estadística & datos numéricos , Síndrome de Dificultad Respiratoria/epidemiología , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Alemania/epidemiología , Encuestas Epidemiológicas , Humanos , Incidencia , Lactante , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , MasculinoRESUMEN
IPEX (immune-dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome is an autoimmune disorder with an often lethal outcome in spite of immunosuppressive therapy. We report the successful use of sirolimus in 3 patients with IPEX. The efficacy of sirolimus is probably due to its different mode of action compared to calcineurin-dependent agents.
Asunto(s)
Inmunosupresores/uso terapéutico , Poliendocrinopatías Autoinmunes/tratamiento farmacológico , Sirolimus/uso terapéutico , Niño , Humanos , Masculino , Poliendocrinopatías Autoinmunes/genética , Poliendocrinopatías Autoinmunes/fisiopatología , SíndromeRESUMEN
We describe a fatal case of encephalitis that might be correlated with primary human metapneumovirus (HMPV) encephalitis. Postmortem HMPV RNA was detected in brain and lung tissue samples from the patient. Furthermore, HMPV RNA was found in culture fluids from cells coincubated with lung tissue.