Joseph R. Hageman

Role of platelet activating factor and tumor necrosis factor-alpha in neonatal necrotizing enterocolitis

Because previous investigations have suggested that platelet activating factor and tumor necrosis factor-alpha (TNF-alpha) are important mediators of experimental necrotizing enterocolitis in the rat, we measured platelet activating factor, acetylhydrolase (the platelet activating factor breakdown enzyme), and TNF-alpha in the plasma of 12 human neonates with necrotizing enterocolitis and eight age-matched control subjects with similar gestational ages, postnatal ages, and weights. Almost all patients with necrotizing enterocolitis had elevated plasma platelet activating factor values (18.1 +/- 3.6 ng/ml vs. 3.1 +/- 0.9 ng/ml in control subjects, p less than 0.01). Plasma acetylhydrolase activity was lower in patients than in control subjects (10.6 +/- 0.7 nmol/ml/min vs 23.0 +/- 1.4 nmol/ml/min, p less than 0.01). Plasma TNF-alpha concentration was significantly elevated in patients with necrotizing enterocolitis (136 +/- 75 U/ml vs 1.5 +/- 0.8 U/ml, p less than 0.05), although the individual variation was high. There was no correlation between individual TNF-alpha and platelet activating factor levels. We conclude that platelet activating factor and TNF-alpha are elevated in patients with necrotizing enterocolitis and that suppressed platelet activating factor degradation contributes to the increased platelet activating factor levels; platelet activating factor and TNF-alpha may contribute to the pathophysiology of necrotizing enterocolitis.

Anticardiolipin antibody -positive serum enhances endothelial cell platelet-activating factor production

Circulating antiphospholipids have been linked to recurrent pregnancy loss by a mechanism involving placental and decidual thrombosis. We hypothesized that platelet-activating factor, an autacoid synthesized by vascular endothelium, might mediate this phenomenon through its ability to promote platelet aggregation and fibrin deposition. Alternatively, antiphospholipid antibodies might exert a procoagulant effect by inhibiting the synthesis of prostacyclin. To evaluate these theories, endothelial cells (harvested from human umbilical veins) were grown to confluence and incubated for 48 hours with 20% concentrations of anticardiolipin antibody-positive and -negative human sera as well as fetal bovine serum. After incubation culture wells were stimulated with 10 mumol/ml calcium ionophore A23187 (an agonist of platelet-activating factor and prostacyclin synthesis). Intracellular platelet-activating factor was measured by tritiated acetate incorporation, phospholipid extraction, thin-layer chromatography, and scintillation spectrophotometry. Enhanced platelet-activating factor synthesis was identified in cultures incubated with anticardiolipin antibody-positive serum (25,544 +/- 2604 disintegrations per minute, mean +/- SD) when compared with anticardiolipin antibody-negative serum (18,600 +/- 3316 dpm) or fetal bovine serum (19,014 +/- 4233 dpm; analysis of variance, p = 0.033). In similar experiments, prostacyclin synthesis was determined by measuring its primary metabolite, 6-keto-prostaglandin F1 alpha, in culture supernatants. No differences between anticardiolipin antibody-positive and control cultures were observed (analysis of variance, p = 0.90). We conclude that in this endothelial cell model, anticardiolipin antibody-positive serum enhances ionophore-mediated platelet-activating factor synthesis but has no apparent effect on the production of prostacyclin. These findings suggest a potential role for platelet-activating factor in anticardiolipin antibody-mediated vascular thrombosis.

Very high-dose ergocalciferol is effective for correcting vitamin D deficiency in children and young adults with cystic fibrosis

Approximately 10-80% of patients with Cystic Fibrosis (CF) have vitamin D deficiency. Obtaining therapeutic vitamin D levels has been a challenge for CF care providers using current recommended high-dose oral ergocalciferol (400,000 IU over 2 months). The objective of this study was to evaluate the safety and efficacy of a 2-week, very high dose ergocalciferol (700,000 IU over 14 days) repletion strategy in children and young adults with CF. As part of a quality improvement initiative, a prospective cohort study was performed from January through May 2007. Phase I included identifying individuals with CF who were subtherapeutic in 25-OH D. In phase II, 50,000 IU of ergocalciferol was prescribed for a 14 day term and administered daily. During phase III, a post treatment 25-OH D level was obtained to determine improvement. Baseline demographics and clinical characteristics were obtained at study entry. Stratification of the post 25-OHD levels was defined. Eighteen individuals with CF participated in the study. The mean age was 17+/-5 years (range 6-25 years). One hundred percent were pancreatic insufficient and required pancreatic enzyme replacement. All 18 had 25-OHD levels less than 30 ng/mL pre-treatment. Seventeen of the 18 (94%) participants became therapeutic in the 2-week interval. No patients had values considered high abnormal (100-150 ng/mL) or toxic (>150 ng/mL). Mean change was noted at an increase of 37.3+/-22 ng/mL in the 2-week period (p<0.001). Pre and peripubertal individuals had a significantly greater increase in 25-OH D levels. The results of this study demonstrate that very high dosing of vitamin D using oral ergocalciferol over a 14 day period is an effective strategy in achieving therapeutic levels of 25-OH vitamin D in children and young adults with CF. We believe this regimen deserves further study.

Exchange transfusion in neonatal myasthenia

TRANSIENT NEONATAL MYASTHENIA OCCURS in 10 to 15% of infants of myas then ic mothers . The illness is character ized by hypotonia , feeding difficulties, and facial weakness, which usually resolve in four to six weeks. Many infants require in te rmi t ten t ant ichol ines terase medication to assure adequa te oral nutr i t ion, bu t f l ank respiratory fai lure is rare. W h e n a severely affected, respiratorbound in fan t failed to respond to ant ichol ines terase medicat ion, exchange t ransfusion produced a significant improvemen t in strength.

Role of Ureaplasma urealyticum in bronchopulmonary dysplasia.

Rappel des recherches tentees pour le traitement de la dysplasie bronchopulmonaire (DBP). Rappel de la microbiologie de U. urealyticum; role dans la pathologie genitale et possiblement dans la pathologie pulmonaire du premature. Interet de poursuivre la recherche sur une eventuelle association entre colonisation par U. urealyticum et DBP

Autoimmune Polyendocrine Syndrome: A Case-Based Review

You are seeing a 14-year-old white male athlete with atopy who complains of a 6-month history of progressive proximal muscle weakness, which significantly impacts his ability to run short distances and swing his baseball bat. His mother states he has presented to multiple emergency departments (ED) for continued weakness and that most diagnosed him with dehydration and educated the family on how to maintain fluid balance. At his last ED visit, a creatine kinase (CK) level was drawn and found to be elevated at 1,247 U/L (normal range 9-185 U/L). A referral to a neurologist was made. The neurologist noted worsening fatigue, dizziness, and a documented 17-pound weight loss at the patient’s initial visit. A possible infectious versus progressive inflammatory myositis was suspected. The neurologist recommended an electromyography (EMG) to evaluate the patient’s proximal muscle weakness. Prior to completion of this EMG, the teen presents to your clinic now complaining of pre-syncopal events. On further review of symptoms, you note the patient has persistent polydipsia, headaches, nausea/vomiting, intermittent abdominal pain, and hyperpigmentation. Family history is negative for myopathies or dystrophies, but positive for hypothyroidism (mother), pineal gland tumor s/p resection (father), and rheumatoid arthritis (maternal grandmother). PHYSICAL EXAMINATION Initial physical examination reveals an afebrile, thin, adolescent male with orthostatic blood pressure changes of 113/59 mm Hg at rest and 89/44 mm Hg while standing; a pulse of 87 beats/ min; and a respiratory rate of 16 breaths/ min. His HEENT exam reveals equally reactive pupils with moist mucous membranes and no thyromegaly. His neurologic exam including cranial nerves, mental status, speech, gait, and coordination is unremarkable; there is no tremor noted. His muscle strength is noted to be 4/5 in the quadriceps bilaterally but 5/5 throughout the rest of his muscle groups. His muscle bulk and tone are mildly decreased. His cardiovascular, pulmonary, and abdominal exams are all benign. He has physiologic pubertal gynecomastia with mild tenderness. His genitourinary examination reveals normal appearing Tanner 3 male genitalia. His skin exam is remarkable for diffuse hyperpigmentation, which extends into his intertriginous areas and most notably the palms and creases of his hands. Flexor surfaces on his arms and diffuse areas on his face show ecAutoimmune Polyendocrine Syndrome: A Case-Based Review

Tuberculosis in Infancy in the 1990s

In 1990, 25,701 cases of tuberculosis (TB) were reported in the United States, the largest annual increase since 1953. Children younger than 15 years of age accounted for 1596 new cases. The resurgence of TB can largely be contributed to the HIV epidemic. The clinical course, diagnosis, therapy, and prevention of TB in the perinatal period and in infancy are discussed in view of the epidemics of HIV and TB in the adult population.

Current variability of clinical practice management of pediatric diabetic ketoacidosis in Illinois pediatric emergency departments.

Objective This study aimed to investigate the management of pediatric patients with diabetic ketoacidosis (DKA) presenting to emergency departments (EDs) participating in the Illinois Emergency Medical Services for Children (EMSC) Facility Recognition program. Methods In 2010, Illinois EMSC conducted a survey (including case scenarios) and medical record review regarding management of pediatric patients with DKA. Data were submitted by 116 EDs. Results Survey response rate was 94%. Only 34% of EDs had a documented DKA guideline/policy; 37% reported that they did not have hospital adult or pediatric endocrinology services. Case scenarios identified a high percentage of respondents given an intravenous (IV) isotonic sodium chloride solution of 10 to 20 mL/kg during the first hour. However 17% to 21% would use an alternative choice such as administering initial IV solution of 0.45 sodium chloride, initiating an insulin drip before fluids, or waiting for more laboratory results before giving fluids or insulin. A total of 532 medical record reviews were submitted. In 87% of records, patients received an initial IV isotonic sodium chloride solution within the first hour. In 74%, patients received IV insulin infusion/drip (0.1 U/kg/h) after the initial fluid bolus. Of the patients, 51% were transferred to another facility; 22% were admitted to an intensive care unit. Conclusions Best ED practice management of pediatric DKA includes establishing a specific guideline/protocol and ensuring access to a pediatric endocrinologist. Both were identified as improvement areas in this project. Illinois EMSC has developed an educational module and provided direct feedback to all participating EDs, to improve their management of pediatric patients with DKA.

Effect of home monitoring on a high-risk population.

A large cohort of infants (8,998) at high risk for sudden and unexpected death was followed with home cardiorespiratory monitoring over a five-year period. These infants included premature infants (23-36 weeks post-conceptual age), SIDS siblings, and infants who experienced an Apparent Life-Threatening Event. The overall SIDS rate in this high-risk population was 0.55/1,000, a rate significantly less than the 0.85 deaths/1,000 reported in the “general population” of Georgia over this same time period. In addition, we report our experience with using home monitors as a diagnostic tool, as well as how monitors can actually be cost-effective.Editorial opinions, and lay press summaries of the CHIME study (JAMA, May 2, 2001) imply that home cardiorespirtory monitors are of little value. Despite the fact that the study never made this claim, many clinicians are now referring to this study as evidence that home monitoring is ineffective and not needed.This article disputes those misconceptions about home cardiorespiratory monitors based on our experience with a large high-risk population of infants.

Cardiopulmonary Resuscitation of the Newborn: An Update

The abrupt transition from intrauterine to extrauterine life represents a series of profound physiologic changes. This process puts the baby at risk for asphyxia. At birth, the newborn is, therefore, more frequently in need of resuscitation than at any other age. This article reviews the rationale for the sequence and process of neonatal resuscitation, emphasizing recent changes in recommendations.