RESUMEN
The high risk of vaso-occlusive events in children younger than 4 years with cyanotic congenital heart disease and polycythaemia has been attributed to increased thromboxane (Tx) A2 formation. In older children with cyanotic congenital heart disease, however, the risk of vaso-occlusive events is much lower. We therefore hypothesized that the formation of TxA2 and prostacyclin is not disturbed in this age group. We measured urinary excretion of stable index metabolites of in vivo TxA2 and prostacyclin formation by gas chromatography-mass spectrometry in nine children (age 5.9-14.4, median 8.7 years) with cyanotic congenital heart disease, and in nine healthy, age-matched control subjects. The patients excreted less 2,3-dinor-TxB2 (systemic TxA2 formation, P = 0.03), 2,3-dinor-6-keto-PGF1 alpha (systemic prostacyclin formation. P = 0.03) and TxB2 (renal TxA2 formation, P = 0.01) than the control subjects. We conclude that in children older than 5 years with cyanotic congenital heart disease, endogenous synthesis of TxA2 and prostacyclin is not stimulated. This result may explain the lower risk of vaso-occlusive events in this age group as compared with younger children. In addition, our results suggest that chronic hypoxaemia may affect the in vivo formation of TxA2 and prostacyclin and the metabolic disposition of TxB2.
Asunto(s)
Epoprostenol/biosíntesis , Cardiopatías Congénitas/metabolismo , Hipoxia/metabolismo , Tromboxano A2/biosíntesis , Adolescente , Niño , Preescolar , Epoprostenol/orina , Femenino , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/orina , Humanos , Hipoxia/complicaciones , Hipoxia/orina , Masculino , Estadísticas no Paramétricas , Tromboxano A2/orinaRESUMEN
OBJECTIVE: Inhaled nitric oxide is a potent and selective pulmonary artery vasodilator. We studied the effects of nitric oxide inhalation in neonatal and pediatric acute respiratory distress syndrome (ARDS) patients with respect to dosage, prolonged inhalation, and weaning. DESIGN: Prospective, open-label study. SETTING: Neonatal and pediatric intensive care units of a level three university hospital. PATIENTS: Seventeen patients with severe ARDS (1 day to 6 yrs of age [mean 1.75]; oxygenation index of > 20 cm H2O/torr) were enrolled. INTERVENTIONS: To identify the optimal dosage for continuous nitric oxide inhalation, doses between 1 and 80 parts per million (ppm) of nitric oxide were tested after the patients had stabilized. Daily withdrawals of nitric oxide were made, according to predetermined criteria. MEASUREMENTS AND MAIN RESULTS: Nine neonatal and eight pediatric ARDS patients (mean Pediatric Risk of Mortality score 28.4 +/- 6.1; mortality risk 54 +/- 15%) were studied. The following variables changed within 24 hrs of nitric oxide inhalation: mean oxygenation index decreased by 56% (from 34 +/- 12 to 15 +/- 7 cm H2O/torr, p = .0004); alveolar-arterial O2 gradient decreased by 31% (from 579 +/- 71 to 399 +/- 102 torr (77.2 +/- 9.5 to 53.2 +/- 13.6 kPa), p = .0004); and mean systemic arterial pressure increased by 15% (from 49 +/- 10 to 57 +/- 12 mm Hg, p = .0029). The optimal dose of nitric oxide was 20 ppm in neonates (with additional persistent pulmonary hypertension of the newborn) and 10 ppm in pediatric patients. Prolonged inhalation (4 to 21 days) was associated with continuous improvement of oxygenation. An oxygenation index of < 5 cm H2O/torr predicted successful withdrawal, with a sensitivity of 75% and a specificity of 89%. None of the patients had to be rescued with extracorporeal membrane oxygenation and 16 of the 17 patients survived. CONCLUSIONS: Inhaled nitric oxide enhances pulmonary gas exchange, with concomitant hemodynamic stabilization, in neonatal and pediatric ARDS. Best effective doses were 10 ppm of nitric oxide in pediatric ARDS and 20 ppm in neonates. Treatment should be continued until an oxygenation index of < or = 5 cm H2O/torr is achieved. Effects on outcome need verification in larger controlled trials.
Asunto(s)
Óxido Nítrico/administración & dosificación , Intercambio Gaseoso Pulmonar/efectos de los fármacos , Síndrome de Dificultad Respiratoria del Recién Nacido/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Administración por Inhalación , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Estudios Prospectivos , Respiración Artificial , Desconexión del VentiladorRESUMEN
The cDNA encoding the ribosomal protein P2 antigen was cloned from a human cDNA library constructed in the lambda gt11 expression vector. A beta-galactosidase-P2 fusion protein was purified to near homogeneity and used to develop an ELISA which was highly specific for anti-P antibodies produced in murine and human SLE. The median concentration of human IgG anti-P antibodies in serum was estimated to be 100 micrograms/ml (range 6-450 micrograms/ml). Pre-incubation of human anti-P sera with a synthetic peptide, corresponding to the C-terminal 22 amino acids of P2, completely inhibited reactivity with the fusion protein in the ELISA. These findings confirm that lupus anti-P sera show a striking restriction in epitope specificity and indicate that the P2 fusion protein is a useful alternative to the synthetic peptide antigen for detection and quantification of anti-P antibodies. To investigate the possibility that anti-P antibodies were induced by 'altered-self', cDNA encoding P2 were also cloned from lupus patients and control mononuclear cells. The predicted amino acid sequences of the patients' P2 were identical to that of the normal controls indicating that a primary structural abnormality of the P2 autoantigen was unlikely.
Asunto(s)
Autoanticuerpos/análisis , Lupus Eritematoso Sistémico/inmunología , Fosfoproteínas/inmunología , Proteínas Recombinantes de Fusión , Proteínas Recombinantes , Proteínas Ribosómicas/inmunología , Secuencia de Aminoácidos , Autoantígenos , Ensayo de Inmunoadsorción Enzimática , Humanos , Leucocitos Mononucleares/inmunologíaRESUMEN
The sera of 56 children with active seronegative juvenile rheumatoid arthritis were examined for the presence of hidden IgM rheumatoid factors (RF) by use of a rapid new method consisting of ion exchange chromatography and an ELISA assay. Elevated hidden IgM-RF levels were detected in 57% of all patients (median value 0.6 IU/ml, p less than 0.01), in 67% of patients with polyarticular disease (1.1 IU/ml, p less than 0.005), in 62% of the group with monoarticular disease (0.6 IU/ml, p less than 0.02), and in 60% of the group with systemic disease (0.6 IU/ml, NS). Whereas hidden IgM-RF plays no role in HLA-B27 positive disease, we found raised titers in 86% of B27 negative patients (0.8 IU/ml, p less than 0.001).