RESUMEN
Differences in avidity between HIV-1 antibodies transmitted passively and antibodies synthesized by children born to HIV-1-positive mothers can be measured using a commercially available competitive enzyme immunoassay kit. The avidity determination method is based on the competition between an anti-HIV-1-peroxidase-labeled antibody at a stable and known concentration and the anti-HIV-1 antibodies (IgA, IgG, IgM) present in the child's serum at various and increasing dilutions. The shift in the competition/dilution curves between serum samples taken at the third and the sixth month of the child's life showed either the loss or the synthesis of anti-HIV-1 antibodies. The antibody avidity determination combined with a test detecting free or complexed p24 antigen is a workable and inexpensive serological method for the follow-up of children born to seropositive mothers. Combining these two complementary methods, HIV-1 infection has been established at 6 months of age in 13 of 13 infants, and positive results were confirmed by coculture and by PCR. An HIV-1 infection was excluded at 6 months of age in 17 of 17 infants, results otherwise confirmed by virological and clinical follow-up. These new and convenient approaches to the diagnosis of vertically acquired HIV-1 could be used worldwide, including in developing countries.
Asunto(s)
Afinidad de Anticuerpos , Complejo Antígeno-Anticuerpo/inmunología , Anticuerpos Anti-VIH/inmunología , Infecciones por VIH/diagnóstico , VIH-1/inmunología , Serodiagnóstico del SIDA/métodos , Análisis de Varianza , Unión Competitiva , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Anticuerpos Anti-VIH/biosíntesis , Anticuerpos Anti-VIH/sangre , Proteína p24 del Núcleo del VIH/sangre , Proteína p24 del Núcleo del VIH/inmunología , Infecciones por VIH/inmunología , Infecciones por VIH/transmisión , Humanos , Inmunidad Materno-Adquirida , Técnicas para Inmunoenzimas , Lactante , Recién Nacido , Reacción en Cadena de la Polimerasa , EmbarazoRESUMEN
We present a case of EBV-induced cerebral B cell lymphoproliferation of donor origin after HLA-matched allogeneic BMT for AML. The presentation was note-worthy as this 4-year-old girl was grafted after a conditioning regimen without irradiation, with an unmanipulated, HLA-matched graft. Furthermore, the cerebral mass developed long after reduction of immunosuppressive therapy following improvement of severe GVHD. To our knowledge, such cerebral lymphoproliferation, under these transplant conditions, has never been described.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Neoplasias Encefálicas/etiología , Leucemia Mieloide Aguda/terapia , Linfoma de Células B/etiología , Southern Blotting , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/virología , Preescolar , ADN Viral/análisis , Femenino , Herpesvirus Humano 4/genética , Prueba de Histocompatibilidad , Humanos , Inmunohistoquímica , Linfoma de Células B/patología , Linfoma de Células B/virología , Trasplante HomólogoRESUMEN
From the present study devoted to the follow-up of 26 children (20 girls and 6 boys) having a tall stature, three major points have emerged: (1) an excessive acceleration of the speed of growth is characteristic of abnormal heights; (2) an endocrine disorder is responsible for the accelerated growth in 50 percent of the cases, and (3) when the cause cannot be determined or suspected by clinical examination, measurement of bone age is the first parameter to be requested.
Asunto(s)
Estatura/fisiología , Enfermedades del Sistema Endocrino/fisiopatología , Crecimiento , Adolescente , Determinación de la Edad por el Esqueleto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Obesidad/fisiopatología , Pubertad Precoz/fisiopatología , Aumento de PesoAsunto(s)
Neumonía por Pneumocystis/prevención & control , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Preescolar , Femenino , Humanos , Tolerancia Inmunológica/inmunología , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/microbiologíaAsunto(s)
ADN Viral/sangre , Proteína p24 del Núcleo del VIH/sangre , Infecciones por VIH/congénito , VIH-1/aislamiento & purificación , Complicaciones Infecciosas del Embarazo , Viremia/congénito , Adulto , Secuencia de Bases , Estudios de Cohortes , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/microbiología , Infecciones por VIH/transmisión , VIH-1/inmunología , Humanos , Lactante , Recién Nacido , Leucocitos Mononucleares/microbiología , Intercambio Materno-Fetal , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Embarazo , Estudios Prospectivos , Provirus/aislamiento & purificación , Viremia/microbiologíaAsunto(s)
Transfusión Sanguínea , Sangre Fetal/citología , Antígenos HLA/inmunología , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Preescolar , Familia , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Histocompatibilidad , Humanos , Recién Nacido , Masculino , Inducción de Remisión , Subgrupos de Linfocitos T/patología , Donantes de TejidosAsunto(s)
Leucemia/diagnóstico , Niño , Preescolar , Humanos , Lactante , Leucemia/sangre , Pronóstico , Factores de RiesgoRESUMEN
UNLABELLED: Sickle cell disease (SCD) is the most common genetic disorder to affect Blacks. The mortality rate associated with SCD has remained high despite the use of appropriate interventions to manage the various forms of crisis. In developed countries, newborn screening programmes are conducted routinely, which has resulted in a reduction in the SCD mortality rate from 16% to <1%. In developing countries where the disease is prevalent, newborn screening programmes are yet to be established, and the acceptability of such programmes by the parents of newly delivered infants is unknown. OBJECTIVES: This study was carried out to determine the acceptability of newborn screening for SCD on mothers of newly delivered infants, and to establish disease prevalence amongst a newborn population in Nigeria. STUDY DESIGN: This prospective cross-sectional study was conducted at St. Philomena's Hospital, Benin City with mothers of newly delivered infants and their newborn babies. METHODS: Newly delivered mothers were recruited consecutively into the study. Knowledge of their own haemoglobin phenotype status was assessed, and their wishes regarding SCD screening of their babies were determined. Babies were screened using isofocusing electrophoresis. RESULTS: Six hundred and thirty mothers, delivered of 649 babies, were recruited into this study. Nineteen sets of babies were twins. Two mothers refused screening for their babies and 628 mothers or caregivers accepted screening; hence the acceptance rate was 99.7%. Four hundred and fifty-seven (71%) mothers did not know their own haemoglobin phenotype. Six hundred and forty-seven babies were screened for SCD. Of these, two samples were lost to testing and one baby had an indeterminate result; these three cases were not included in the analysis. Of the 644 babies whose results were analysed, 332 (51.6%) were male, 312 (48.4%) were female, 485 (75.3%) were AA, 133 (20.6%) were AS, seven (1.1%) were AC, 18 (2.8%) were SS, and one (0.2%) was SC. CONCLUSION: The majority of mothers in this study did not know their haemoglobin phenotype. Newborn screening for SCD was acceptable to 99.7% of the mothers. The prevalence of SCD in the newborn population was 3% (2.8% SS and 0.2% SC).
Asunto(s)
Anemia de Células Falciformes/diagnóstico , Tamizaje Neonatal , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Recién Nacido , Masculino , Madres , Nigeria , Consentimiento Paterno , Estudios ProspectivosRESUMEN
OBJECTIVE: Among the mechanisms suggested for altered consciousness during cerebral malaria is the hypothesis of cerebral ischemia, which remains controversial, with little supportive O2 conflicting hemodynamic data. The purpose of this study was to test the hypothesis that cerebral ischemia is a main mechanism for altered consciousness during cerebral malaria. SETTING: University hospital pediatric ward in a region with endemic cerebral malaria. DESIGN: Prospective evaluation of cerebral hemodynamics and cerebral oxygenation during cerebral malaria compared with severe malaria anemia without altered consciousness. PATIENTS: During a 2-wk period, we evaluated all patients who were admitted for cerebral malaria (n = 5). Age-matched patients admitted for severe malaria anemia without altered consciousness (n = 3) and outpatients (n = 3) were investigated for comparison. INTERVENTIONS: All patients received the usual treatment according to their needs, which was determined by the physician in charge. Repeated neurologic evaluations were performed during the early management period in patients with cerebral malaria. METHODS AND MAIN RESULTS: We repeatedly measured cerebral blood flow velocity (transcranial Doppler) and simultaneous systemic determinants of cerebral blood flow (arterial pressure, arterial oxygen saturation, PaCO2, rectal temperature, and hemoglobin concentration). The adequacy of cerebral blood flow to oxygen demands during cerebral malaria was assessed by continuous recording of jugular bulb venous oxygen saturation (using a fiberoptic device). Marked cerebral vasodilation was observed during cerebral malaria (systolic velocity, 1.45 +/- 0.09 m/s; diastolic velocity, 0.75 +/- 0.08 m/s; n = 4) and during severe malaria anemia (systolic velocity, 1.18 +/- 0.14 m/s; diastolic velocity, 0.55 +/- 0.05 m/s; n = 3) compared with control children (systolic velocity, 0.84 +/- 0.13 m/s; diastolic velocity, 0.35 +/- 0.06 m/s; n = 3; p < .05). During cerebral malaria, jugular bulb venous oxygen saturation remained stable, including during neurologic recovery, with initial values of 67.5 +/- 4.3%. CONCLUSIONS: Because jugular bulb venous oxygen saturation remained within the normal range, cerebral hyperemia seems to be an adaptive response to altered systemic determinants, which argues against a hemodynamic mechanism for altered consciousness during cerebral malaria.
Asunto(s)
Anemia/fisiopatología , Isquemia Encefálica/etiología , Encéfalo/irrigación sanguínea , Estado de Conciencia , Malaria Cerebral/fisiopatología , Malaria Falciparum/complicaciones , Anemia/etiología , Velocidad del Flujo Sanguíneo , Isquemia Encefálica/fisiopatología , Circulación Cerebrovascular , Preescolar , Femenino , Escala de Coma de Glasgow , Hemodinámica , Humanos , Lactante , Malaria Cerebral/clasificación , Malaria Cerebral/complicaciones , Masculino , Estudios Prospectivos , Ultrasonografía Doppler TranscranealRESUMEN
We have developed a strategy based on polymerase chain reaction (PCR) for detecting all possible gamma T-cell receptor (gamma TCR) rearrangements and the most common delta TCR rearrangements found in B-lineage and T-acute lymphoblastic leukemia (T-ALL). The segments amplified from blasts are then directly sequenced to derive clonospecific probes. From a series of 45 patients aged 1 to 15 years (42 B-lineage ALL, 3 T-ALL), 35 (83%) could be followed for minimal residual disease with at least one clonospecific probe. Detection of clonal markers using clonospecific probes routinely allowed the detection of 1 to 10 blasts out of 10(5) cells as determined by serial dilutions of the initial samples. Residual disease was quantitated by a competitive PCR assay based on the coamplification of an internal standard. Twenty children were prospectively followed for periods varying from 7 to 30 months. In most children, a progressive decrease of the tumor load was observed, and blasts became undetectable within 6 months after the initiation of treatment. A slower kinetics of decrease in tumor cells was found in three children. These three patients relapsed with blasts that continued to display the initial clonospecific markers. Three other children had a central nervous system relapse despite the absence of detectable medullary residual disease. The use of both delta and gamma TCR genes as clonal markers, as well as simplification in the methods to detect and quantify residual blasts reported here, will allow the study of the large number of patients required to determine the role of the detection of minimal residual disease by PCR in the follow-up of childhood ALL.
Asunto(s)
Reordenamiento Génico de la Cadena delta de los Receptores de Antígenos de los Linfocitos T , Reordenamiento Génico de la Cadena gamma de los Receptores de Antígenos de los Linfocitos T , Reacción en Cadena de la Polimerasa , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Adolescente , Secuencia de Bases , Niño , Preescolar , Estudios de Seguimiento , Humanos , Lactante , Datos de Secuencia Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Estudios ProspectivosRESUMEN
Busulfan disposition is age-dependent with a higher clearance and a larger volume of distribution in children than in adults. The optimal dosage of busulfan needed to achieve bone marrow (BM) displacement in young children with malignant or nonmalignant disease remains to be defined. Using a gas chromatography-mass spectrometry assay, we evaluated plasma pharmacokinetics of busulfan in 33 children (median age, 9 months; range, 2 months to 2.75 years) with immune deficiencies, lysosomal storage diseases, acute leukemias, and malignant lymphohistiocytosis after an oral dose ranging from 0.9 to 2.6 mg/kg. The busulfan clearance (assuming a bioavailability of 1) ranged from 2.1 to 13.4 mL/min/kg with a mean of 6.8 mL/min/kg, which is higher than that reported in older children (4.5 mL/min/kg) and adults (2.9 mL/min/kg). Six children with lysosomal storage disease (5 with Hurler's disease, 1 with San Filippo's disease) had a prolonged elimination half-life (4.9 v 2.4 hours), a larger volume of distribution (3.4 v 1.2 L/kg) and a faster clearance (8.7 v 6.3 mL/min/kg) than the other 27 children. This suggests that a higher dose of busulfan will be required to achieve BM displacement in children with lysosomal storage disease. Over the dose range of 0.9 to 2.6 mg/kg, busulfan pharmacokinetics were linear. However, only 46% of the interpatient variation in systemic exposure could be ascribed to the dose. Given the wide interpatient variability in busulfan disposition, dose adjustment and drug monitoring will be needed to achieve the optimal dosage of busulfan in young children. The plasma busulfan levels required to achieve BM displacement need to be defined, especially in lysosomal storage diseases.