Norma B Lerner

National Institutes of Health | NIH · DBDR

Objective: The aim of this preliminary study was to describe putative markers of cerebral vasculopathy and investigate relationships among these markers, demographic factors, and cognitive function in a young sample of neurologically normal children with SCD. Study Design. Thirty-eight children with homozygous HbS, aged 4-11 years, were included....

Patients in the pediatric intensive care unit (PICU) frequently receive transfusions of blood products. While these therapies are often beneficial, they can be associated with significant, yet often overlooked, risks. Clinical guidelines for blood product transfusions must be well defined in order to prevent misuse of this limited resource. It is i...

Bacteremia is one of the most feared infectious complications of sickle cell disease, and it is associated with a high mortality rate in children. The objective of our study was to investigate the proportion of bacteremia among febrile children with sickle hemoglobinopathies and the clinical factors associated with bacteremia. Clinical and microbio...

Children undergoing cardiac surgery with cardiopulmonary bypass are susceptible to additional inflammatory and immunogenic insults from blood transfusions. We hypothesize that washing red blood cells and platelets transfused to these patients will reduce postoperative transfusion-related immune modulation and inflammation. Prospective, randomized,...

To determine whether subjects of Puerto Rican heritage are at increased risk for a specific mutation of the proton-coupled folate transporter (PCFT) causing hereditary folate malabsorption (HFM). Three percent of the births in Puerto Rico in 2005, with additional regional oversampling, were screened for the prevalence of the c.1082G>A; p.Y362_G389...

Aspirin is often used to prevent thrombosis in pediatric cardiac surgery. The primary study aim was to assess aspirin resistance in this context. Secondary aims were to evaluate (1) the relationship between elevated inflammatory markers and thrombosis and (2) aspirin's effect on these levels. This was a prospective observational study of children u...

To examine the impact of a restrictive vs. liberal transfusion strategy on arterial lactate and oxygen content differences in children with single-ventricle physiology post cavopulmonary connection. Children with single-ventricle physiology are routinely transfused postoperatively to increase systemic oxygen delivery, and transfusion thresholds in...

Cerebral arteriopathies, including an idiopathic focal cerebral arteriopathy of childhood (FCA), are common in children with arterial ischemic stroke and strongly predictive of recurrence. To better understand these lesions, we measured predictors of arteriopathy within a large international series of children with arterial ischemic stroke. Between...

To assess local trends in the incidence of sickle cell disease (SCD) and hemoglobin (Hb) S trait. Hemoglobinopathy clinic follow-up and cohort mortality rates were also evaluated. A longstanding newborn hemoglobinopathy screening program was reviewed. Incidence rates were computed with information from a confidential database, specialty clinic/hosp...

To determine if soluble CD40 ligand (sCD40L; formally CD154) levels vary with age and to identify age-dependent ranges in healthy pediatric and adult populations. sCD40L was measured in 25 neonates, 74 children (3 months-15 years of age) and 20 adults using an enzyme-linked immunosorbent assay. For age group comparisons, Mann-Whitney tests were per...

Thrombotic events cause significant morbidity and mortality in children who undergo surgery for complex congenital cardiac disease. We prospectively evaluated the incidence of thrombosis and examined preoperative and postoperative laboratory tests of coagulation and inflammation in neonates experiencing initial surgical palliation for variations of...

Children with sickle cell disease are at risk of developing neurologic complications, including stroke, transient ischemic attack, seizures, coma, and a progressive reduction in cognitive function. Transcranial Doppler ultrasound, magnetic resonance imaging, and overnight pulse oximetry appear to predict, making prevention an achievable goal so tha...

Hemoglobin (Hb) Bassett, an abnormal Hb variant with a markedly reduced oxygen affinity, was discovered in a Caucasian (Anglo-Saxon) male child who experienced episodes of cyanosis. Cation-exchange and reversed-phase (RP) high-performance liquid chromatography (HPLC) showed that the patient has an abnormal Hb, with a mutation in the alpha-globin. T...

The impact of peripheral blood stem cell transplantation (PBSCT) on survival relative to bone marrow transplantation (BMT) remains poorly defined. Several randomized controlled trials (RCTs) comparing HLA-matched related PBSC- and BMT for patients with hematologic malignancies have been published, yielding differing results. We conducted a meta-ana...

Fibrinogen (FBG), together with its polymerized form fibrin, modulates cellular responses during wound repair and tissue remodeling. Thus, we sought to determine whether A549 lung epithelial type II-like cells would endocytose insoluble, surface-bound FBG as a potential mechanism of alveolar matrix remodeling. Surface-bound FBG was endocytosed into...

Fibrinogen (FBG), together with its polymerized form fibrin, modulates cellular responses during wound repair and tissue remodeling. Thus, we sought to determine whether A549 lung epithelial type Ii-like cells would endocytose insoluble, surface-bound FBC as a potential mechanism of alveolar matrix remodeling. Surface-bound FBC was endocytosed into...

We present a case of arterial thrombosis of the upper extremity in a 1-day-old neonate. The initial response to thrombolytic and anticoagulant therapy alone was unsuccessful. Distal flow to the extremity was reestablished by combined percutaneous transluminal angioplasty of the subclavian artery using transumbilical access followed by resumption of...

The vascular endothelial cell (EC) is a primary target of infection with Rickettsia rickettsii, the etiologic agent of Rocky Mountain spotted fever. Changes in gene transcription elicited by intracellular infection, including EC expression of the coagulation pathway initiator known as tissue factor (TF), may contribute to the vascular pathology obs...

Rickettsia rickettsii, the etiologic agent of Rocky Mountain spotted fever, is an obligate intracellular bacterial organism that infects primarily the vascular endothelial cells (EC). A component of the EC response to infection is transcriptional activation, which may contribute to the thrombotic and inflammatory consequences of disease. In this st...

The c-kit proto-oncogene encodes a 145- to 160-Kd transmembrane tyrosine kinase, which is a member of the platelet-derived growth factor receptor family and is allelic with the murine white spotting locus (W). W mutations affect several aspects of hematopoiesis, most notably erythroid progenitors and mast cells. A monoclonal antibody, YB5.B8, had b...

Cardiac dysfunction is the most common cause of death in patients with homozygous +/--thalassemia. We studied a group of 10 older patients (mean age 17.5 years) with and without preexisting cardiac dysfunction who had begun chelation therapy on the average of 10 years after regular transfusions were initiated. Over the 4-year study period, two pati...

Cardiac dysfunction is the most common cause of death in patients with homozygous +/--thalassemia. We studied a group of 10 older patients (mean age 17.5 years) with and without preexisting cardiac dysfunction who had begun chelation therapy on the average of 10 years after regular transfusions were initiated. Over the 4-year study period, two pati...

The current status of gene transfer experiments indicates that it is possible to provide (1) safe and efficient retroviral packaging lines for gene transfer; and (2) vectors containing the human beta-globin genes and selectable marker genes which can be transmitted into erythroid cells and are appropriately expressed. In animal autologous bone marr...

The principals of gene theraphy, although superficially simple, involve three important prerequisites: (1)Gene Transfer, (2) Gene Pression, (3) Safety.

A retroviral vector containing a 4.4-kb Pst I human beta S-globin gene and a neomycin resistance gene was used to infect NIH-3T3 and mouse erythroleukemia cells (MELC). In MELC, human beta-globin mRNA transcripts are transcribed and properly initiated and spliced. In some cases, there is an appropriate increase in beta-globin mRNA on addition of di...

We report here an evaluation of 55 pregnancies at risk for a sickle hemoglobinopathy prenatally diagnosed by restriction-endonuclease analysis, with the endonucleases MstII and HpaI, of amniocyte DNA. The diagnosis was completed in all cases. Eleven fetuses were predicted to be affected, of which six were terminated. Forty-one of the 55 cases were...

Human globin genes can be transferred into mouse and human erythroid cells in culture, and can be appropriately expressed at the mRNA level in these cells. A plasmid containing a human beta globin gene is expressed in mouse erythroleukemia cells (MELC), and another containing a human epsilon or gamma gene is expressed in human erythroleukemia (K562...