RESUMO
BACKGROUND: Somatic mutations affecting components of the Ras-MAPK pathway are a common feature of cancer, whereas germline Ras pathway mutations cause developmental disorders including Noonan, Costello, and cardio-facio-cutaneous syndromes. These 'RASopathies' also represent cancer-prone syndromes, but the quantitative cancer risks remain unknown. METHODS: We investigated the occurrence of childhood cancer including benign and malignant tumours of the central nervous system in a group of 735 individuals with germline mutations in Ras signalling pathway genes by matching their information with the German Childhood Cancer Registry. RESULTS: We observed 12 cases of cancer in the entire RASopathy cohort vs 1.12 expected (based on German population-based incidence rates). This corresponds to a 10.5-fold increased risk of all childhood cancers combined (standardised incidence ratio (SIR)=10.5, 95% confidence interval=5.4-18.3). The specific cancers included juvenile myelomonocytic leukaemia=4; brain tumour=3; acute lymphoblastic leukaemia=2; rhabdomyosarcoma=2; and neuroblastoma=1. The childhood cancer SIR in Noonan syndrome patients was 8.1, whereas that for Costello syndrome patients was 42.4. CONCLUSIONS: These data comprise the first quantitative evidence documenting that the germline mutations in Ras signalling pathway genes are associated with increased risks of both childhood leukaemia and solid tumours.
Assuntos
Síndrome de Costello/genética , Displasia Ectodérmica/genética , Insuficiência de Crescimento/genética , Cardiopatias Congênitas/genética , Neoplasias/epidemiologia , Síndrome de Noonan/genética , Proteínas ras/genética , Adolescente , Criança , Pré-Escolar , Síndrome de Costello/patologia , Displasia Ectodérmica/patologia , Fácies , Insuficiência de Crescimento/patologia , Feminino , Mutação em Linhagem Germinativa , Alemanha/epidemiologia , Cardiopatias Congênitas/patologia , Humanos , Lactente , Masculino , Neoplasias/etiologia , Neoplasias/patologia , Síndrome de Noonan/patologia , Sistema de Registros , Fatores de Risco , Transdução de SinaisRESUMO
Introduction.The crossover sign (CS) is proposed in the diagnosis of pincer-type femoroacetabular impingement (FAI). CS occurs in the cranial region of the acetabulum while the acetabular version angle (AV) is measured in the region where the acetabulum becomes deeper. Objective. To determine whether AV values measured in cranial regions using the classical measures relate better to the findings for positive CS. Material and Methods. Cross sectional study in asymptomatic patients. Images were obtained by CT of the abdomen and pelvis. They were recored in anterior-posterior reconstruction the CS and in axial reconstruction the AV angle. Logistic regression models for measuring AV in 7 cephalic levels to caudal with 95 percent CI were estimated. Results. 104 patients were measured. At Level 3 an area under ROC curve 0.81 (0.74-0.87), cutoff value of 11.2 degrees with sensitivity of 80.0 percent and specificity of 73.0 percent, was obtained. Conclusion. AV at level 3 has higher diagnostic capacity for the presence of positive CS.
Introducción. El signo de entrecruzamiento (SE) es propuesto en el diagnóstico imagenológico del pinzamiento Femoroacetabular tipo Pincer. El SE se produce en la región craneal del acetábulo, mientras que el ángulo de versión acetabular (VA) se mide en la región donde el acetábulo se hace más profundo. Objetivo. Determinar si valores de VA medidos en regiones craneales a la medida clásica se relacionan mejor al hallazgo de SE positivo. Material y Método. Estudio transversal en pacientes asintomáticos. Se obtuvieron imágenes mediante TC de abdomen y pelvis. Fueron consignados en reconstrucción antero-posterior el SE y en reconstrucción axial el ángulo de VA. Se estimaron modelos de regresión logística para la medición de VA en 7 niveles de cefálico a caudal con IC 95 porciento. Resultados. Fueron medidos 104 pacientes. En nivel 3 se obtuvo un área bajo curva ROC 0.81 (0.74-0.87), valor de corte 11.2 grados con sensibilidad de 80.0 porciento y especificidad de 73.0 porciento. Conclusión. VA en nivel 3 tiene mayor capacidad diagnóstica de la presencia de SE positivo.
Assuntos
Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Acetábulo/patologia , Acetábulo , Impacto Femoroacetabular , Tomografia Computadorizada por Raios X , Curva ROC , Estudos Transversais , Modelos LogísticosRESUMO
Nineteen childhood near drowning cases admitted to a private general hospital from December 31, 1983 through out December 1987 at a mean age of 2 years 3 months are discussed. All patients had diagnosis when first found by relatives, 16 were apneic and only 11 received some kind of resuscitation which complied with accepted standards in 4 of them. Seven cases were admitted in stage A of Conn, two in stage B and ten in stage C. In six children in stage C intracranial pressure (ICP) monitoring was done and ICP was increased in two that died. Five patients developed clinical and radiological evidence of non cardiogenic pulmonary edema and 4 had hypotension sometime along the first 24 hours, requiring fluid therapy and inotropic drugs. Four patients died, all of them were in stage C when admitted. One child shows severe brain damage four years after discharge. The main complications after resuscitation were hemodynamic instability, pulmonary problems and hypoxic encephalopathy. High ICP was not important in the first hours and when it rose it did so 24 to 48 hours after admission. The need for an active role in prevention, improved resuscitation and transport, is stressed.
