Defective glycosylation and multisystem abnormalities characterize the primary immunodeficiency XMEN disease.

X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia (XMEN) disease are caused by deficiency of the magnesium transporter 1 (MAGT1) gene. We studied 23 patients with XMEN, 8 of whom were EBV naive. We observed lymphadenopathy (LAD), cytopenias, liver disease, cavum septum pellucidum (CSP), and increased CD4-CD8-B220-TCRαβ+ T cells (αβDNTs), in addition to the previously described features of an inverted CD4/CD8 ratio, CD4+ T lymphocytopenia, increased B cells, dysgammaglobulinemia, and decreased expression of the natural killer group 2, member D (NKG2D) receptor.

A Unique Heterozygous Mutation Combines Pathogenic Features of Both Gain- and Loss-of-Function Patients in a Four-Generation Family.

CARD11 is a lymphocyte-specific scaffold molecule required for proper activation of B- and T-cells in response to antigen. Germline gain-of-function (GOF) mutations in the gene cause a unique B cell lymphoproliferative disorder known as B cell Expansion with NF-κB and T cell Anergy (BENTA). In contrast, patients carrying loss-of-function (LOF), dominant negative (DN) mutations present with severe atopic disease.

Insights into immunity from clinical and basic science studies of DOCK8 immunodeficiency syndrome.

DOCK8 immunodeficiency syndrome (DIDS) is a progressive combined immunodeficiency that can be distinguished from other combined immunodeficiencies or hyperimmunoglobulinemia E syndromes in featuring (a) profound susceptibility to virus infections of the skin, with associated skin cancers, and (b) severe food allergies. The DOCK8 locus has many repetitive sequence elements that predispose to the generation of large germline deletions as well as recombination-mediated somatic DNA repair. Residual DOCK8 protein contributes to the variable disease phenotype.

Impaired Control of Epstein-Barr Virus Infection in B-Cell Expansion with NF-κB and T-Cell Anergy Disease.

-cell xpansion with F-κB and -cell nergy (BENTA) disease is a B-cell-specific lymphoproliferative disorder caused by germline gain-of-function mutations in . These mutations force the CARD11 scaffold into an open conformation capable of stimulating constitutive NF-κB activation in lymphocytes, without requiring antigen receptor engagement. Many BENTA patients also suffer from recurrent infections, with 7 out of 16 patients exhibiting chronic, low-grade Epstein-Barr virus (EBV) viremia.

Communication plays a critical role in web-based monitoring.

Background: Patient-health care practitioner (HCP) interaction via a Web-based diabetes management system may increase patient monitoring of their blood glucose (BG) levels.

Methods: A three-center, nonrandomized, prospective feasibility study of 109 Native Americans with poorly controlled type 1 diabetes mellitus and type 2 diabetes mellitus were recruited from Alabama, Idaho, and Arizona. The study intervention included the use of a Web-based diabetes management application (MyCareTeam) that allowed timely interaction between patients and HCPs.

Dorsal penile nerve block vs topical placebo for circumcision in low-birth-weight neonates.

Objective: To investigate the efficacy and safety of dorsal penile nerve block (DPNB) and eutectic mixture of lidocaine (EMLA) for palliation of pain associated with circumcision in low-birth-weight infants.

Design: Randomized, blinded, controlled trial.

Setting: Intensive care nursery (step down unit) at Georgetown University Medical Center, Washington, DC.

Zinc absorption, distribution, excretion, and retention by healthy preterm infants.

Zinc (Zn) is an essential nutrient for growth, but little is known about Zn absorption, distribution, excretion, and retention in preterm infants. Nine infants with gestational age 32+/-1 wk (mean+/-SE), birth weight 1.44+/-0.

Zinc kinetics in preterm infants: a compartmental model based on stable isotope data.

Zinc is an essential nutrient for growth; however, little is known about zinc kinetics (absorption, distribution, and excretion) in preterm infants (< 38-wk gestation). Zinc kinetics were studied in two preterm infants (gestational ages, 32 and 33 wk) following oral or intravenous administration of a stable isotope (70Zn). Plasma, red blood cells (RBC), urine, and feces were sampled for up to 30 days.

Effect of human milk or formula on gastric function and fat digestion in the premature infant.

The effect of diet, human milk or formula, on gastric function (lipase and pepsin activity, pH, and volume) and intragastric digestion of fat was assessed in 28 appropriate for gestational age preterm infants (gestational age, 28.9 +/- 1.4, 29.

Effect of necrotizing enterocolitis on urinary epidermal growth factor levels.

The pattern of urinary epidermal growth factor/creatinine levels in necrotizing enterocolitis was examined in 75 infants (in 28 infants the diagnosis of necrotizing enterocolitis was considered; 47 infants were studied for effect of surgery or nutrition on epidermal growth factor levels). There was a consistent and significant increase in epidermal growth factor/creatinine values at the time of diagnosis of necrotizing enterocolitis compared with baseline values. Epidermal growth factor levels in infants without necrotizing enterocolitis and in early nutrition remained unchanged.

Developmental pattern of urinary epidermal growth factor in the premature infant and the influence of gender.

We report the cross-sectional pattern of first day urinary epidermal growth factor/creatinine (EGF/Cr) levels in 159 appropriate for gestational age infants born at 26-41 weeks gestation. EGF/Cr levels rose significantly earlier in female infants than levels in male infants. In female infants levels were similar to term levels beginning at 30-32 weeks.

Quantification of neonatal cerebral ventricular volume by real-time ultrasonography. In vivo validation of the cylindrical coordinate method.

Posthemorrhagic ventricular dilation is a common clinical problem in preterm infants who have incurred an intraventricular hemorrhage. Presently there are no clinically applicable methods to follow quantitatively the progression of ventricular dilation at bedside. We describe the in vivo validation of a method to measure ventricular volume using bedside real-time cranial ultrasonography.

Effect of congenital renal disease and neonatal thyroid status on urinary human epidermal growth factor concentrations.

We have previously demonstrated that changes in urinary epidermal growth factor/creatinine ratios relate to gestational age and gender. It is unclear what controls this developmental pattern although chronic renal disease and thyroid aberrations have significant effects on epidermal growth factor and creatinine excretion in childhood and in adults. Therefore, we chose to explore the effects of these disease states on epidermal growth factor excretion during the perinatal time period.

The need for a loading dose of gentamicin in neonates.

We studied pharmacokinetic variables in 100 neonates to evaluate the need for a loading dose of gentamicin. The mean volume of distribution for gentamicin in this population was .542 +/- .

Cardiac output determinations in the newborn. Reproducibility of the pulsed Doppler velocity measurement.

Cardiac output (QAo) can be estimated noninvasively by pulsed Doppler (PD) ultrasonographic determination of mean ascending aortic blood flow velocity (VAo) combined with M-mode echocardiographic determination of ascending aortic cross sectional area (AAo). Cardiac output is calculated from the volumetric flow equation (QAo) = (VAo) X (AAo). Pulsed Doppler measurements are known to correlate well with Fick and thermodilution methods; however, inter- and intraoperator variability of the velocity component of the PD method has not been determined in newborns.

Longitudinal trends in left ventricular cardiac output in healthy infants in the first year of life.

We studied left ventricular (LV) cardiac output as estimated by ascending aorta blood flow (QAo) longitudinally in 31 healthy infants from birth through the first year of life using noninvasive pulsed Doppler ultrasound technique. The temporal mean ascending aortic blood flow velocity (VAo) was measured with a 5-MHz pulsed Doppler velocimeter and on line integration system. Ascending aortic cross-sectional area (AAo) was determined using M-mode echography.

Effect of patent ductus arteriosus on gentamicin pharmacokinetics in very low birth weight (less than 1,500 g) babies.

The effect of patent ductus arteriosus (PDA) and its therapy on the pharmacokinetic disposition of gentamicin in very low birth weight neonates was studied. Twenty-four neonates weighing less than 1,500 g with PDA were compared to 16 patients without PDA. Patients with PDA had significantly greater apparent volumes of distribution (0.

Exaggerated jaundice in Navajo neonates. The role of bilirubin production.

We have explored further the mechanism of exaggerated neonatal hyperbilirubinemia in the Navajo by determining bilirubin production rates with measurements of endogenous carbon monoxide excretion. Navajo newborns had elevated serum bilirubin concentrations and endogenous carbon monoxide excretion measurements at 2 days of age compared with a Caucasian control population. These findings could not be explained by differences in gestational age, postnatal age, or hemoglobin concentration.

Oxytocin and neonatal hyperbilirubinemia. Studies of bilirubin production.

We studied the effect of oxytocin induction or augmentation of labor on rates of bilirubin production in newborns at three different institutions. Bilirubin production, assessed quantitatively by the pulmonary excretion rate of carbon monoxide or qualitatively by the blood carboxyhemoglobin concentration, was not elevated when compared with appropriately matched control groups. Previous studies have implicated administration of large volumes of electrolyte-free dextrose solutions together with oxytocin as an important factor contributing to hemolysis in the infant.

Effect of patent ductus arteriosus on lower extremity blood flow velocity patterns in preterm infants.

We used a 20-MHz, range-gated, pulsed Doppler device to measure noninvasively femoral artery blood flow velocity patterns in 24 preterm infants with patent ductus arteriosus (PDA). Mean spatial flow velocity and its temporal average were recorded by illumination of the entire flow stream. Peak systolic forward flow velocity (Vs), peak diastolic retrograde flow velocity (VD), mean flow velocity (Vf), and the peak to peak-mean velocity ratio, (VS-VD)/Vf, were determined serially in each patient.

Noninvasive measurement of cardiac output in healthy preterm and term newborn infants.

Although values for cardiac output in the newborn infant have been reported previously, the methods utilized have been invasive. To assess if cardiac output could be determined noninvasively in the neonate, we measured mean ascending aortic blood flow velocity (VAo) in well newborns using a portable 5MHz, range gated, pulsed Doppler velocity meter. Measurements were made from a suprasternal approach in 8 preterm (mean birth weight 1718 gm; mean estimated gestation age 33.