RESUMO
BACKGROUND: Cisapride is a prokinetic agent that facilitates gastrointestinal motility and is widely used for the treatment of gastroesophageal reflux disease (GERD) in adults and children. However, reports of ventricular proarrhythmia have been noted in patients taking cisapride, particularly in conjunction with other drugs that may inhibit hepatic metabolism of cisapride via the cytochrome P450 3A4 system. OBJECTIVE: We designed a prospective, blinded study to evaluate the effect of cisapride on ventricular repolarization in children with GERD. METHODS: We analyzed the electrocardiograms (ECGs) from 35 children (age 0.4 to 18 years, mean 5.2 years) including measurement of the resting QT interval (QTc), JT interval (JTc), as well as QT and JT interlead dispersion markers. Data from these patients were compared with ECGs from a control group of 1000 normal children. RESULTS: Eleven (31%) of 35 patients receiving cisapride had a prolonged QTc (> or = 450 ms). The JTc was prolonged > or = 360 ms in 16 of 35 patients (46%). The mean QTc in the cisapride group was 428 +/- 35 ms and mean JTc was 336 +/- 35 ms. An increased QT or JT dispersion (> 70 ms) was seen in only 3 of 35 children. Of the 11 children with QTc prolongation, 2 had documented torsades de pointes ventricular tachycardia. Both patients were taking cisapride concomitantly with a macrolide antibiotic. All other patients were treated with either cisapride alone or in conjunction with other GERD agents, such as ranitidine or omeprazole. CONCLUSIONS: Cisapride may cause prolongation of ventricular repolarization in children. There does not appear to be increased heterogeneity of repolarization or delayed depolarization in this small sample. The proarrhythmia may be exacerbated by medications that inhibit cytochrome P450 3A4 hepatic metabolism, overdosage, or mechanisms that result in decreased serum clearance. ECG intervals should be monitored in children maintained on cisapride, particularly when used in combination with other known QT-prolonging medications.
Assuntos
Eletrocardiografia/efeitos dos fármacos , Fármacos Gastrointestinais/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Piperidinas/efeitos adversos , Adolescente , Criança , Pré-Escolar , Cisaprida , Refluxo Gastroesofágico/tratamento farmacológico , Humanos , Lactente , Estudos Prospectivos , Método Simples-CegoRESUMO
Reduced antibody-dependent cell-mediated cytotoxicity (ADCC) was demonstrated in lymphocytes of patients with rheumatoid arthritis (RA). Rheumatoid factor (RF) positive sera inhibited ADCC of normal lymphocytes by reacting both with effector and target cells (sensitized chicken red blood cells). These sera were fractionated by specific adsorption or gradient ultracentrifugation, and isolated RF or RF negative fractions were tested for their ability to inhibit ADCC by reacting with normal human lymphocytes or target cells. RF was ineffective on normal lymphocytes but it strongly inhibited the reaction by interaction with target cells. IgG RF negative fractions of certain sera were inhibitory by direct interaction with effector cells.