The pediatric hydroxyurea phase III clinical trial (BABY HUG): challenges of study design.

Evidence of the laboratory benefits of hydroxyurea and its clinical efficacy in reducing acute vaso-occlusive events in adults and children with sickle cell anemia has accumulated for more than 15 years. A definitive clinical trial showing that hydroxyurea can also prevent organ damage might support widespread use of the drug at an early age. BABY HUG is a randomized, double-blind placebo-controlled trial to test whether treating young children ages 9-17 months at entry with a liquid preparation of hydroxyurea (20 mg/kg/day for 2 years) can decrease organ damage in the kidneys and spleen by at least 50%.

Terminal ileal atresia, total colonic aganglionosis, and thrombophilia.

Inherited thrombophilia, a predisposition for a hypercoagulable state, has been associated with cases of intestinal atresia. In this communication, we report a case of terminal ileal atresia and total colonic aganglionosis (Hirschsprung's disease), a rarely documented association, in a neonate who seemed to have a hypercoagulable state. The case stresses the need for recognition of this sequence of events in order to achieve optimal management.

Severity of obstructive sleep apnea in children with sickle cell disease.

Objective: To characterize polysomnographic (PSG) findings of children with sickle cell disease (SCD) suspected of having sleep disordered breathing (SDB).

Methods: Families of 100 consecutively referred children with SCD completed the Children's Sleep Habit Questionnaire during a routine visit to identify concerns regarding sleep habits and sleep behavior. Of these, 48 children were identified as displaying behaviors suspicious of SDB.

Human CD34(+) and CD34(+)CD38(-) hematopoietic progenitors in sickle cell disease differ phenotypically and functionally from normal and suggest distinct subpopulations that generate F cells.

Objective: Sickle cell disease (SCD) is remarkable for stress erythropoiesis. We investigated the progenitor populations contributing to erythroid stress.

Materials And Methods: We characterized hematopoietic progenitor cells in sickle bone marrow and sickle peripheral blood from patients with SCD compared to those in normal bone marrow.

Pediatric tumor cells express erythropoietin and a functional erythropoietin receptor that promotes angiogenesis and tumor cell survival.

Erythropoietin was traditionally considered an erythroid-restricted cytokine, but recent evidence indicates a broader role for it in nonhematopoietic tissues, specifically in neural development. Pediatric solid tumors are mostly developmental in origin, and more than 50% of the solid tumors are neural in origin. We found erythropoietin receptor and erythropoietin expression in common pediatric tumor cells: neuroblastomas, Ewing's sarcoma family of tumors, pediatric brain tumors (medulloblastoma, astrocytoma, and ependymoma), Wilms tumors, rhabdomyosarcomas, and hepatoblastomas (n = 24), and in cell lines derived from some of these tumors (n = 25).

Placenta growth factor activates monocytes and correlates with sickle cell disease severity.

Sickle cell disease (SCD) results in chronic hypoxia and secondarily increased erythropoietin concentrations. Leukocytosis and activated monocytes are also observed in SCD in absence of infection or vaso-occlusion (steady state), the reasons for which are unknown. We found that erythroid cells produced placenta growth factor (PlGF), an angiogenic growth factor belonging to the vascular endothelial growth factor (VEGF) family, and its expression was induced in bone marrow CD34+ progenitor cells in the presence of erythropoietin.