R. Brent Scott

Plasma L-arginine concentrations in premature infants with necrotizing enterocolitis

OBJECTIVE To determine whether L-arginine concentrations (the substrate for nitric oxide synthesis) are lower in premature infants in whom necrotizing enterocolitis (NEC) develops than in unaffected infants. METHODS We measured arginine and nutritional intake, plasma arginine, glutamine, total amino acids, and ammonia concentrations in 53 premature infants (mean gestational age +/- SD: 27 +/- 1.7 weeks) at risk of NEC. Measurements were done on days 3, 7, 14 and 21 and just before treatment in infants with NEC. RESULTS Necrotizing enterocolitis developed in 11 infants between postnatal days 1 and 26. On day 3, plasma arginine concentrations were decreased compared with normal published values (mean +/- SE, 41 mumol/L +/- 4). Arginine concentrations increased with day of life of measurement (p < 0.001) and arginine intake (p < 0.001). Plasma arginine concentrations were significantly lower at the time of diagnosis in infants with NEC compared with control subjects, even after adjusting for arginine intake and day of life (p = 0.032). Plasma glutamine and total amino acid concentrations were not significantly different in infants with NEC compared with control subjects. Plasma ammonia concentrations were elevated on day 3 (mean +/- SE, 72 +/- 3.3 mumol/L) and decreased with postnatal age (p < 0.001) and increasing plasma arginine concentrations (p < 0.001). CONCLUSION Plasma arginine concentrations are decreased at the time of diagnosis in premature infants with NEC. The potential benefit of arginine supplementation in the prevention of the disease deserves evaluation.

Prevalence of IgA-antiendomysial antibody in asymptomatic low bone mineral density.

Abstract OBJECTIVE: Celiac disease (CD) is a relatively common gastrointestinal disorder that can be asymptomatic. However, even among asymptomatic patients a long-term reduction in bone mineral density (BMD) is found. Excellent noninvasive screening tests for CD are now available. Studies using older screening techniques have suggested a 10-fold increased prevalence of CD among patients with low BMD, but this has not been confirmed with current testing methodology. We set out to confirm these prevalence estimates using antiendomysial antibody testing. METHODS: A total of 100 consecutive patients referred to our outpatient endocrinology clinic for evaluation of idiopathic low BMD were studied. In addition to the routine evaluation, patients completed a symptom questionnaire and underwent serological testing for the presence of the IgA antiendomysial antibody (EMA). All patients with a positive EMA underwent small bowel biopsy and permeability studies. RESULTS: EMA results were available on 96 patients; 78/96 patients were female and the mean age was 57 yr (range 18–86 yr). Seven of 96 (7.3% [95% CI 2.1–12.5%]) were EMA-positive, but all tests were low titer (≤1:20). However, none of the biopsies showed any histopathological features of CD, nor did EMA status correlate with any of the clinical or laboratory features assessed. CONCLUSIONS: Despite a high rate of weakly positive antibody tests, our data do not support an increased prevalence of CD among asymptomatic patients referred for evaluation of low BMD. Without an increase over the background prevalence, the high cost of EMA testing argues against routine use of this test for screening of this population.

Anaphylaxis-induced mesenteric vascular permeability, granulocyte adhesion, and platelet aggregates in rat

This study investigates the response of small venules to IgE-dependent, antigen-mediated mast cell activation. Intravital microscopy was utilized to visualize 25- to 40-micron mesenteric venules, mast cell degranulation (on-line detection), vascular permeability changes (albumin leakage), leukocyte adhesion, and the formation of platelet aggregates in rats sensitized with 10 microg of intraperitoneal egg albumin (EA) in saline- or sham-sensitized (saline alone) rats. Sensitized rats challenged with EA (1 mg/ml superfusing mesentery), but not sensitized rats challenged with BSA or sham-sensitized rats challenged with EA, exhibited mast cell degranulation with significant time-dependent increases in vascular permeability (inhibited by diphenhydramine, salbutamol, and indomethacin), leukocyte adhesion (inhibited by Web-2086), and the formation of cellular aggregates (platelet), which were associated with intermittent obstruction of venular flow. Anti-platelet antibody, but not anti-neutrophil antibody or fucoidin (selectin antagonist), prevented platelet aggregate formation. Compound 48/80-induced mast cell degranulation caused similar changes in permeability (via different mediators) and leukocyte adhesion but did not induce platelet aggregation. EA-induced platelet aggregation was not inhibited by any of the mediators tested, and platelets isolated from sensitized rats failed to aggregate in response to direct EA challenge, suggesting release of an unidentified inflammatory mediator as the factor initiating platelet aggregation.This study investigates the response of small venules to IgE-dependent, antigen-mediated mast cell activation. Intravital microscopy was utilized to visualize 25- to 40-μm mesenteric venules, mast cell degranulation (on-line detection), vascular permeability changes (albumin leakage), leukocyte adhesion, and the formation of platelet aggregates in rats sensitized with 10 μg of intraperitoneal egg albumin (EA) in saline- or sham-sensitized (saline alone) rats. Sensitized rats challenged with EA (1 mg/ml superfusing mesentery), but not sensitized rats challenged with BSA or sham-sensitized rats challenged with EA, exhibited mast cell degranulation with significant time-dependent increases in vascular permeability (inhibited by diphenhydramine, salbutamol, and indomethacin), leukocyte adhesion (inhibited by Web-2086), and the formation of cellular aggregates (platelet), which were associated with intermittent obstruction of venular flow. Anti-platelet antibody, but not anti-neutrophil antibody or fucoidin (selectin antagonist), prevented platelet aggregate formation. Compound 48/80-induced mast cell degranulation caused similar changes in permeability (via different mediators) and leukocyte adhesion but did not induce platelet aggregation. EA-induced platelet aggregation was not inhibited by any of the mediators tested, and platelets isolated from sensitized rats failed to aggregate in response to direct EA challenge, suggesting release of an unidentified inflammatory mediator as the factor initiating platelet aggregation.

Rat gastric motor response to food protein-induced anaphylaxis

BACKGROUND/AIMS Antigen challenge of sensitized rats leads to delayed gastric emptying, but the mechanism (gastroparesis or prolonged trituration) and mediators are unknown. METHODS Hooded Lister rats were sensitized by intraperitoneal injection of egg albumin as antigen, and control rats were sham-sensitized. On day 14, antral manometric and antroduodenal myoelectric activities in sensitized and sham-sensitized rats were recorded in response to antigen challenge, and the contractility of gastric antral circular muscle strips (mucosa intact) in standard tissue baths was measured in response to antigen or other agents. RESULTS In vivo, the intragastric antigen challenge of sensitized (but not sham-sensitized) rats provoked diarrhea, reduction in the antral motility index, and disruption of the duodenal migrating motor complex. In vitro, antigen induced a tonic contraction of antral circular muscle segments from sensitized animals. Doxantrazole, but not disodium cromoglycate, inhibited antigen-induced contraction. Whereas histamine, 5-hydroxytryptamine, prostaglandins, leukotrienes, and platelet-activating factor contracted gastric muscle strips, neither specific antagonists, prostaglandin synthase, or 5-lipoxygenase inhibitors inhibited antigen-induced contraction. Tetrodotoxin increased antigen-induced contraction; however, the antigen-induced contraction was unaffected by atropine, guanethidine, or NG-nitro-L-arginine methyl ester. CONCLUSIONS Food protein-induced, immunoglobulin E-mediated delayed gastric emptying in sensitized rats is associated with a transient reduction in gastric antral contractions. Antigen-induced contraction appears to be under nonadrenergic, noncholinergic, nonnitroxinergic inhibitory neural control.

Colonic motor response to IgE‐mediated mast cell degranulation in the Hooded‐Lister rat

Abstract After challenge of sensitized individuals, food protein‐induced colonic anaphylaxis may contribute to the symptom of diarrhoea. The aim of this study was to characterize the effect of food protein‐induced anaphylaxis on colonic circular muscle in vitro, identify the mediators involved, and then evaluate the effect of antigen challenge on colonic transit in vivo. Hooded‐Lister rats were sensitized by intraperitoneal injection of egg albumin and controls were sham‐sensitized with saline. Rings of distal colonic tissue were suspended in standard tissue baths (mucosa intact) and circular muscle contractility was measured in response to antigen or other agents on day 14. In conscious animals, Na251CrO4 was instilled alone, or with antigen, via proximal colostomy and the geometric centre of distribution of 51Cr calculated. Following antigen challenge, a contractile response occurred only in animals that were sensitized (specific IgE antibody levels ≥1:64), and was specific for the sensitizing antigen. Mast cell involvement was suggested when (1) concanavalin A (a degranulator of both mucosal and connective tissue mast cells) mimicked the antigen‐induced response, and (2) Ag‐induced contraction was significantly inhibited by mast cell stabilizers. The Ag‐induced response was significantly and independently inhibited by a lipo‐oxygenase enzyme inhibitor and by LTD4 and platelet activating factor receptor antagonists. The antigen‐induced response was resistant to histamine and 5‐hydroxytryptamine receptor antagonists, indomethacin, atropine and tetrodotoxin. The geometric centre of distribution of 51Cr was significantly more distal in sensitized animals challenged with antigen rather than placebo, and only sensitized animals challenged with antigen developed diarrhoea. These results suggest that colonic antigen challenge of sensitized rats is associated with IgE‐mediated mast cell activation, the release of membrane derived mediators which, in vitro, act directly on smooth muscle to induce contraction, and in vivo result in an increased rate of aboral transit and diarrhoea.

PLASMA ARGININE LEVELS DECREASE WITH INCREASING SEVERITY OF RESPIRATORY DISTRESS SYNDROME (RDS) IN PREMATURE BABIES. 1516

PLASMA ARGININE LEVELS DECREASE WITH INCREASING SEVERITY OF RESPIRATORY DISTRESS SYNDROME (RDS) IN PREMATURE BABIES. 1516

PLASMA ARGININE LEVELS AND SYSTEMIC BLOOD PRESSURE (BP) IN PREMATURE BABIES WITH RESPIRATORY DISTRESS SYNDROME (RDS). 1515

Background: Arginine is the substrate for the synthesis of nitric oxide (NO), a potent vasodilator in both the systemic and pulmonary circulation. Case reports have suggested a role for the L-arginine-nitric oxide pathway in neonatal blood pressure regulation (Acta Pediatr, 1995;84:460-2). Objective: To examine the possible relationship between plasma arginine levels and systemic BP in premature babies with RDS.Design: Twenty premature babies with birthweight (BW) ≤ 1250 g requiring mechanical ventilation were studied. Gestational age, 26.5±1.6 weeks; BW, 880±150 g (mean ± SD). Plasma arginine levels and mean systemic BP were measured on days 3, 7, 14 and 21. A random-effects model for longitudinal data (Biometrics, 1982;38:963-74) was used to analyze the influence of the following on BP: plasma arginine levels, use of vasopressors, gestational age, oxygenation index, daily sodium intake and difference between daily fluid intake and diuresis. Results: Use of dopamine was the only significant factor in this model and was negatively correlated with BP (p < 0.01). A positive correlation between plasma arginine levels and BP was suggested but did not reach statistical significance (p=0.056). Conclusion: Plasma arginine levels may be related to BP in premature babies with RDS but after adjusting for the influence of other factors this relation does not reach statistical significance. Speculation: Activation of NO synthetase in babies with RDS may utilize arginine producing lower systemic BP. Alternatively, lower plasma arginine levels may be a manifestation of increased catabolism in babies with lower BP.

Fatal Cholestatic Hepatitis in an Infant: An Unusual Etiology

An infant girl who presented with cholestasis and hepatitis that rapidly progressed to fulminant liver failure is reported. Postmortem examination yielded a diagnosis of demonstrated extensive hepatic necrosis due to adenovirus type 5 infection which had developed in the setting of an occult primary immunodeficiency (severe combined immunodeficiency). The aim of this report is to alert the physician to a rare cause of cholestasis and hepatitis in infancy. Recognition of the combination of adenoviral infection with underlying primary immunodeficiency is a prerequisite to the provision of genetic counselling.

Childhood Ménétriér's Disease: A Rare Cause of Exudative Enteral Protein Loss

A six-year-old boy with Menetriers disease, which developed in association with an intercurrent cytomegalovirus (CMV) infection, is presented. This case illustrates the clinical features, natural history and self-limited nature of this rare cause of exudative protein loss in childhood and provides evidence for the association between CMV infection and the pathogenesis of this disorder.

Childhood Peutz-Jeghers Syndrome: Diversity of Clinical Features and Complications, and Literature Review

This case report of a six-year-old child with Peutz-Jeghers syndrome illustrates the potential diversity of presenting gastrointestinal symptoms and signs including hematemesis, obstruction and recurrent intussusception. Endoscopy was useful in assessment, while endoscopic polypectomy and surgical resection were both necessary for management. The literature is reviewed and the possible role that this syndrome may have in the development of both gastrointestinal and nongastrointestinal tumours is highlighted.