Citations

Objective— Endothelial progenitor cells (EPCs) display a unique aptitude to promote angiogenesis and restore endothelial function of injured vessels. How progenitor cells can execute a regenerative program in the unfavorable environment of injury/inflammation-induced oxidative stress is poorly understood. We hypothesized that EPCs are resistant to oxidative stress and that this resistance is due to high expression and activity of antioxidant enzymes. Methods and Results— EPCs outgrown from human blood of healthy subjects demonstrated a marked resistance to cytotoxic effect of LY83583 (an generator), tumor necrosis factor-α, and serum depletion. LY83583 inhibited in vitro tube formation by human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (CAECs), but not by EPCs. Compared with HUVECs and CAECs, EPCs exhibited ≈3- to 4-fold higher expression and activity of manganese superoxide dismutase (MnSOD), but not copper zinc superoxide dismutase (CuZnSOD) or catalase. The antioxidant profile in EPCs was associated with preservation of the mitochondrial network when exposed to LY83583. Moreover, cytotoxic effects of LY83583 on CAECs and HUVECs were reversed by adenoviral overexpression of MnSOD. Conclusions— Human EPCs are resistant to oxidative stress. High intrinsic expression of MnSOD is a critical mechanism protecting EPCs against oxidative stress.

Background. Although glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is prevalent in African Americans, their risk of associated neonatal hyperbilirubinemia has not been prospectively studied.Objective. To compare hemolysis and the risk of hyperbilirubinemia among African American, G-6-PD-deficient neonates (study group) and G-6-PD-normal control subjects.Methods. Consecutive, healthy, term and near-term, male neonates born to African American mothers comprised the patient cohort. G-6-PD testing was performed with umbilical cord blood samples. Routine management included measurement of the end tidal carbon monoxide level corrected for ambient carbon monoxide level (ETCOc) within 4 hours after delivery (assessment of hemolysis), ≥1 predischarge bilirubin determination, and additional bilirubin testing as clinically indicated. Indications for phototherapy were identical for study patients and control subjects. Neonates were monitored for the first 1 week of life. ETCOc results, the incidence of hyperbilirubinemia (defined as a transcutaneous or plasma total bilirubin concentration of ≥95th percentile for the hour of life), and the need for phototherapy were compared between the G-6-PD-deficient and G-6-PD-normal groups.Results. Five hundred male patients were enrolled, of whom 64 (12.8%) were G-6-PD-deficient. ETCOc values (median and interquartile range) were higher among G-6-PD-deficient neonates than among control neonates (2.4 ppm [2.0–2.9 ppm] vs 2.1 ppm [1.7–2.5 ppm]). More G-6-PD-deficient neonates developed hyperbilirubinemia than did control subjects (14 of 64, 21.9%, vs 29 of 436, 6.7%; relative risk: 3.27; 95% confidence interval: 1.83-5.86), whereas 13 (20.3%) met the criteria for phototherapy, compared with 25 control subjects (5.7%) (relative risk: 3.53; 95% confidence interval: 1.91-6.56). No cases of kernicterus were observed.Conclusions. Within the African American neonatal population, there is a subgroup of G-6-PD-deficient infants with elevated rates of hemolysis, a higher incidence of hyperbilirubinemia, and a greater requirement for phototherapy, compared with G-6-PD-normal control subjects. These newborns should be monitored vigilantly for the development of hyperbilirubinemia.

Objectives. To characterize the clinical features, results of diagnostic testing, and treatment outcomes for children and adolescents with rumination syndrome. Methods. Review of the medical records for all 147 patients ages 5 to 20 diagnosed with rumination syndrome at our institution between 1975 and 2000. Data are presented as mean ± the standard error of the mean. Results. Sixty-eight percent were female. Age at diagnosis was 15.0 ± 0.3 years. Symptom duration before diagnosis was 2.2 ± 0.3 years, 73% missed school/work, and 46% had been hospitalized because of symptoms. Before diagnosis, 16 (11%) underwent surgery for evaluation or management of symptoms. Twenty-four (16%) had psychiatric disorders; 3.4% had anorexia or bulimia nervosa. All patients described postprandial regurgitation after almost every meal (2.7 ± 0.1 meals per day). Weight loss was described by 42.2% (median: 7 kg). Additional symptoms included: abdominal pain, 38%; constipation, 21%; nausea, 17%; and diarrhea, 8%. Structural studies were normal. Gastric emptying of solids at 4 hours was delayed in 26 of 56 patients. Esophageal pH testing in 24 patients showed reflux/regurgitation in 54%. Gastroduodenal manometry in 65 patients showed characteristic rumination-waves in 40%. Outcome data (at median follow-up 10 months) were available for 54 patients. Symptoms resolved in 16 (30%) and improved in 30 (56%). Conclusions. Recognition of the clinical features of rumination syndrome in children and adolescents is essential; the diagnosis is often delayed and associated with morbidity. Extensive diagnostic testing is unnecessary. Early behavioral therapy is advocated, and patient outcomes are generally favorable.

Objective. The development of this review article evolved from a National Kidney Foundation consensus conference on recent advances in the importance of evaluating and treating proteinuria. From this conference, a series of recommendations for the evaluation of adults with proteinuria was published. Because specific pediatric aspects of the problem were outside the scope of the original National Kidney Foundation publication, an ad hoc committee of 6 pediatric nephrologists who were active participants in the National Kidney Foundation conference was established to provide primary care physicians with a concise, up-to-date reference on this subject. Methods. The recommendations that are given represent the consensus opinions of the authors. These are based on data from controlled studies in children when available, but many of the opinions are, by necessity, based on uncontrolled series in children or controlled trials performed in adults, because controlled trials in children have not been performed to evaluate many of the treatments described. Results and Conclusions. These recommendations are intended to provide primary care physicians with a useful reference when they are faced with a young child or teenager who presents with proteinuria, whether this is mild and asymptomatic or more severe, leading to nephrotic syndrome.

Objective— Mechanisms of renal injury distal to renal artery stenosis (RAS) remain unclear. We tested the hypothesis that it involves microvascular remodeling consequent to increased oxidative stress. Methods and Results— Three groups of pigs (n=6 each) were studied after 12 weeks of RAS, RAS+antioxidant supplementation (100 IU/kg vitamin E and 1 g vitamin C daily), or controls. The spatial density and tortuousity of renal microvessels (<500 μm) were tomographically determined by 3D microcomputed tomography. The in situ production of superoxide anion and the expression of vascular endothelial growth factor (VEGF), its receptor VEGFR-2, hypoxia-inducible-factor (HIF)-1α, von Hippel-Lindau (VHL) protein, and NAD(P)H oxidase (p47phox and p67phox subunits) were determined in cortical tissue. RAS and RAS+antioxidant groups had similar degrees of stenosis and hypertension. The RAS group showed a decrease in spatial density of cortical microvessels, which was normalized in the RAS+antioxidant group, as was arteriolar tortuousity. RAS kidneys also showed tissue fibrosis (by trichrome and Sirius red staining), increased superoxide anion abundance, NAD(P)H oxidase, VHL protein, and HIF-1α mRNA expression. In contrast, expression of HIF-1α, VEGF, and VEGFR-2 protein was downregulated. These were all significantly improved by antioxidant intervention. Conclusions— Increased oxidative stress in the stenotic kidney alters growth factor activity and plays an important role in renal microvascular remodeling, which can be prevented by chronic antioxidant intervention.