RESUMEN
BACKGROUND: BAY 81-8973 is a new full-length human recombinant factor VIII product manufactured with technologies to improve consistency in glycosylation and expression to optimize clinical performance. OBJECTIVES: To demonstrate superiority of prophylaxis vs. on demand therapy with BAY 81-8973 in patients with severe hemophilia A. PATIENTS/METHODS: In this multinational,randomized, open-label crossover study (LEOPOLD II;ClinicalTrials.gov identifier: NCT01233258), males aged 1265 years with severe hemophilia A were randomized to twice-weekly prophylaxis (20-30 IU kg(-1)), 3-times-weekly prophylaxis (30-40 IU kg(-1)), or on-demand treatment with BAY 81-8973. Potency labeling for BAY 81-8973 was based on the chromogenic substrate assay or adjusted to the one-stage assay. Primary efficacy endpoint was annualized number of all bleeds (ABR). Adverse events (AEs)and immunogenicity were also assessed. RESULTS: Eighty patients (on demand, n = 21; twice-weekly prophylaxis, n = 28; 3-times-weekly prophylaxis, n = 31) were treated and analyzed. Mean ± SD ABR was significantly lower with prophylaxis (twice-weekly, 5.7 ± 7.2; 3-times-weekly, 4.3 ± 6.5; combined, 4.9 ± 6.8) vs. on-demand treatment (57.7 ± 24.6; P < 0.0001, ANOVA). Median ABR was reduced by 97% with prophylaxis (twice-weekly, 4.0;3-times-weekly, 2.0; combined, 2.0) vs. on-demand treatment (60.0). Median ABR was higher with twice-weekly vs. 3-times-weekly prophylaxis during the first 6-month treatment period (4.1 vs. 2.0) but was comparable in the second 6-month period (1.1 vs. 2.0). Few patients reported treatment-related AEs (4%); no treatment-related serious AEs or inhibitors were reported. CONCLUSIONS: Twice weekly or 3-times-weekly prophylaxis with BAY 81-8973 reduced median ABR by 97% compared with on-demand therapy, confirming the superiority of prophylaxis. Treatment with BAY 81-8973 was well tolerated.
Asunto(s)
Coagulantes/administración & dosificación , Factor VIII/administración & dosificación , Hemofilia A/tratamiento farmacológico , Proteínas Recombinantes/administración & dosificación , Adolescente , Adulto , Anciano , Asia , Niño , Coagulantes/efectos adversos , Estudios Cruzados , Esquema de Medicación , Monitoreo de Drogas/métodos , Europa (Continente) , Factor VIII/efectos adversos , Hemofilia A/sangre , Hemofilia A/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , América del Norte , Proteínas Recombinantes/efectos adversos , Índice de Severidad de la Enfermedad , Sudáfrica , América del Sur , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Ebstein's disease is a congenital malformation of the tricuspid valve that causes various hemodynamic alterations depending on the anatomic changes in the valve, presence or absence of atrial septal defect and reduction in the ventricular function. We present 19 patients with Ebstein's malformation of the tricuspid valve younger than 2 years of age. The long-term follow-up was from 1 week to 16 years with a mean of 40 months. Eight children died, 6 were lost in the follow-up and 5 survived. Early cyanosis with associated lesions give a bad prognosis. If the child survives the first year of life he has a better long term prognosis.
Asunto(s)
Anomalía de Ebstein/fisiopatología , Arritmias Cardíacas/fisiopatología , Presión Sanguínea , Anomalía de Ebstein/patología , Femenino , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
Acute rheumatic fever (ARF) is associated with disseminated inflammation and tissue lesions with heavy fibrin deposition, specially in heart valves and myocardium. The immune pathogenesis of ARF has been suspected, but not satisfactorily proven. An active cellular immune reaction generates cell activators (lymphokines) from T cells, which are able to induce a procoagulant activity (PCA) in mononuclear cells. We studied PCA in peripheral blood mononuclear cells isolated form ARF patients as well as normal controls. The PCA from ARF was 1.5 to 15 times higher than the PCA from controls. This activity was associated with the presence of C-reactive protein and other acute phase markers. The PCA from mononuclear cells in ARF may be one of the mechanisms responsible for fibrin deposition.
Asunto(s)
Proteína C-Reactiva/análisis , Monocitos/análisis , Fiebre Reumática/inmunología , Adolescente , Coagulación Sanguínea , Niño , Femenino , Humanos , Linfocinas/metabolismo , Masculino , Fiebre Reumática/sangre , Linfocitos T/inmunología , Linfocitos T/metabolismoRESUMEN
In utero infection by rubella virus is a well known cause of congenital heart disease. We look for prevalence of anti-rubella antibodies of IgM (primary response) or IgG (anamnestic response) classes in sera of 32 children with congenital heart disease and in 12 normal children of the same socioeconomic background. Only in a patient with a full congenital rubella syndrome we found high titers of IgG anti-rubella antibodies, there was no difference in prevalence of IgM nor IgG anti-rubella antibodies between normals and cardiac patients. There is no reason to look for anti-rubella antibodies in the isolated congenital heart disease.
Asunto(s)
Anticuerpos Antivirales/análisis , Cardiopatías Congénitas/inmunología , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Virus de la Rubéola/inmunología , Preescolar , Femenino , Enfermedades Fetales/complicaciones , Enfermedades Fetales/inmunología , Cardiopatías Congénitas/etiología , Humanos , Lactante , Masculino , Embarazo , Rubéola (Sarampión Alemán)/complicaciones , Rubéola (Sarampión Alemán)/congénito , Rubéola (Sarampión Alemán)/inmunologíaRESUMEN
We compared clinical and immunological characteristics of acute rheumatic fever (19 cases) and infectious endocarditis (7 cases), because these two diseases can be confused easily with each other and their differential diagnosis is not simple. In this small series we had cases of acute rheumatic fever with splenomegaly and/or vasculitis, as well as infectious endocarditis with subcutaneous nodules, which exemplifies the diagnostic problem. Using laboratory tests we were able to point out differences which are statistically significant, such as: rheumatoid factor by passive agglutination of IgG sensitized latex particles (X2 4.27 p less than 0M05), and tests which reflects the presence of circulating immune complexes, hemolytic capacity of antigammaglobulin antibodies (X2 3.79 p less than 0.05) and the presence of circulating C3 degradation products (X2 5.92 p less than 0.01), which occurs preferentially or exclusively in infectious endocarditis. Although in the standard patient the clinical assessment is usually sufficient to establish a diagnosis, when differentiation between acute rheumatic fever and infectious endocarditis is not clear, immunologic tests are helpful.
Asunto(s)
Endocarditis Bacteriana/diagnóstico , Fiebre Reumática/diagnóstico , Adolescente , Adulto , Niño , Diagnóstico Diferencial , Endocarditis Bacteriana/inmunología , Femenino , Humanos , Masculino , Fiebre Reumática/inmunología , Factor Reumatoide/análisisRESUMEN
Two cases of double-chambered right ventricle without ventricular septal defect are presented. Both were diagnosed with the hemodynamic study and underwent successful surgical repair. We discuss the probable embryologic development and the diagnostic procedures of this malformation.