Allergic proctitis and gastroenteritis in children. Clinical and mucosal biopsy features in 53 cases.

We have reviewed 53 cases of allergic disorders of the gastrointestinal tract in children, including 15 with principal effects in the rectum (allergic proctitis) and 38 with dominant involvement of the upper and mid portions of the gut (allergic gastroenteritis). Most cases of allergic proctitis had their onset at less than 6 months of age, and all were under 2 years old when they presented with rectal bleeding alone or in combination with diarrhea. Rectal mucosal biopsy revealed in most cases a diffuse increase of eosinophils in the lamina propria together with a focal infiltration of the epithelium by eosinophils. Cases of allergic gastroenteritis affected all age groups and had a lower frequency of overt rectal bleeding. More common were other symptoms (vomiting, pain, and weight loss), an allergic history, anemia, blood eosinophilia, and increased serum IgE. Mucosal biopsy abnormalities were present in the gastric antrum in all cases sampled, the small intestine in 79%, the esophagus in 60%, and the gastric corpus in 52%. The lesions were usually diffuse and marked in the antrum and esophagus; in contrast, they tended to be focal and mild in the small intestine and gastric corpus. All cases of proctitis responded to a dietary change by cessation of symptoms without recurrences, whereas most of those with gastroenteritis had multiple relapses and required corticosteroid therapy.

Cricopharyngeal dysfunction associated with Chiari malformations.

UNLABELLED: Dysphagia due to upper esophageal sphincter (UES) dysfunction can be a manifestation of Chiari malformation. We evaluated five young children with dysphagia and a Chiari malformation before and after craniocervical decompression. Preoperatively, esophageal manometry with a multilumen perfused catheter revealed failure of complete relaxation of the UES in three patients, pharyngo-UES incoordination in one patient, and both abnormalities in the last patient. Preoperative barium esophagograms were obtained in four of the patients and were normal in two. One patient had nasal regurgitation of barium and delayed passage of barium through the UES. One patient had a posterior pharyngeal impression (bar) at the level of the UES and delayed transit of barium. All patients had clinical and manometric resolution of UES dysfunction following surgical decompression of the Chiari malformation. All swallows were coordinated, and UES relaxations were complete. However, the posterior pharyngeal bar persisted on postoperative esophagogram in the only patient who had had the abnormality preoperatively, although it no longer interfered with passage of barium. Another patient had a narrowed UES with decreased relaxation. Swallowing was radiographically normal in three patients postoperatively. CONCLUSION: Surgical decompression of Chiari malformation may lead to complete clinical and manometric resolution of dysphagia due to upper esophageal sphincter dysfunction. Esophageal manometry is more likely than barium swallow to demonstrate the abnormality, and correlates better with symptomatic improvement postoperatively.

Barth's syndrome-like disorder: a new phenotype with a maternally inherited A3243G substitution of mitochondrial DNA (MELAS mutation).

An Argentine male child died at 4.5 years of age of a lethal mitochondrial disease associated with a MELAS mutation and a Barth syndrome-like presentation. The child had severe failure to thrive from the early months and for approximately two years thereafter. In addition, the patient had severely delayed gross motor milestones, marked muscle weakness, and dilated cardiomyopathy that progressed to congestive heart failure. He also had persistently elevated urinary levels of 3-methylglutaconic and 2-ethylhydracrylic acids and low blood levels of cholesterol. Detailed histopathologic evaluation of the skeletal muscle biopsy showed high activity of succinate dehydrogenase, a generalized decrease of COX activity, and abundant ragged-red fibers. Electron microscopic studies revealed multiple mitochondrial abnormalities in lymphocytes and monocytes, in the striated muscle, and in the postmortem samples (muscle, heart, liver, and brain). Biochemical analysis showed a pronounced and constant lactic acidosis, and abnormal urinary organic acid excretion (unchanged in the fasting and postprandial states). In addition, in CSF there was a marked increase of lactate and beta-hydroxybutyrate (beta-HOB) and also a high systemic ratio beta-HOB/acetoacetate. Enzymatic assay of the respiratory chain in biopsied muscle showed 10% of complex I activity and 24% of complex IV activity compared with controls. Molecular studies of the mitochondrial genome revealed an A to G mutation at nucleotide pair 3243 in mitochondrial DNA, a well-known pathogenetic mutation (MELAS mutation) in all the patient's tissues and also in the blood specimens of the probands mother and sibs (4 of 5). The diagnosis of MELAS mutation was reinforced by the absence of an identifiable mutation in the X-linked G4.5 gene of the propositus. The present observation gives additional evidence of the variable clinical expression of mtDNA mutations in humans and demonstrates that all clinical variants deserve adequate investigation to establish a primary defect. It also suggests adding Barth-like syndrome to the list of phenotypes with the MELAS mutation.

Stridor and gastroesophageal reflux: diagnostic use of intraluminal esophageal acid perfusion (Bernstein test).

Five pediatric patients with stridor were evaluated to determine whether gastroesophageal reflux (GER) contributed to their stridor. Intraluminal esophageal acid perfusion (Bernstein test), pH probe, radiographic studies, laryngobronchoscopy, and esophageal histology were utilized. Thereafter, three of the five patients responded to therapy for GER; two did not. The Bernstein test proved to have greater diagnostic reliability than any other test employed, using response to antireflux therapy as the "gold standard" for diagnosing reflux-provoked stridor.

Soluble interleukin-2 receptor levels in infants with bronchopulmonary dysplasia.

Soluble interleukin-2 receptors (sIL2R) in plasma have been identified as a marker of lymphocyte activation. Lymphocyte activation as a manifestation of inflammation may be important in the pathogenesis of bronchopulmonary dysplasia (BPD). To test the hypothesis that infants with BPD have higher sIL2R levels, 12 infants with or at risk of developing BPD (GA +/- SD, 27 +/- 5 weeks; BW +/- SD 1,053 +/- 733 g) had plasma sIL2R levels determined and were compared to 20 infants being ventilated for respiratory distress syndrome (RDS) (GA +/- SD, 28 +/- 3.5 weeks; BW +/- SD, 1,133 +/- 390 g: P = NS for both GA and BW, t test). Tracheal aspirates in both groups were also analyzed for sIL2R levels. To control for the effects of postnatal age (PNA) and study weight (SW) on the sIL2R levels, another group of 16 nonventilated babies (NVB) had plasma analyzed for sIL2R (PNA +/- SD: 39 +/- 40 days NVB vs. 48 +/- 36 days BPD; P = NS); (SW +/- SD: 1391 +/- 250 g NVB vs. 1212 +/- 700 g BPD; P = NS). The following data were obtained for the plasma sIL2R levels (mean +/- SEM U/mL): RDS controls, 1,231 +/- 80; BPD infants, 1,790 +/- 120; NVB controls, 1,319 +/- 76; P = 0.0005 RDS vs. BPD and P = 0.002 BPD vs. NVB. There was no significant difference in the sIL2R levels for the infants at risk of developing BPD vs. the infants with established BPD. Also, when analyzed separately, infants at risk of BPD and the infants with established BPD had higher sIL2R levels than the RDS and NVB controls. No differences were noted in the tracheal sIL2R levels in the BPD vs. RDS groups. These data indicate that infants with BPD had significantly higher sIL2R levels in plasma than either RDS or NVB controls. Therefore, lymphocyte activation may play a role in the pathogenesis of BPD.

Prevalence and characteristics of Blastocystis hominis infection in children.

Blastocystis hominis, a protozoan whose pathogenicity has been questioned, is sometimes found in the human gastrointestinal tract. We sought to determine the prevalence of Blastocystis in stool and to characterize clinical features of infection with Blastocystis in children. Forty-six (3%) of 1,736 patients undergoing fecal microscopy at Children's Hospital of Pittsburgh between January 1, 1985, and December 31, 1988, harbored Blastocystis. Of these 46 children, 75% had exposure to well water or had been in developing countries. Thirty-nine of the 46 (85%) experienced gastrointestinal symptoms, such as abdominal pain, diarrhea, vomiting, and weight loss. Blastocystis was the only parasite found in 35 of those 39 symptomatic children. Symptoms resolved within one month in 90% of patients receiving antiparasitic pharmacotherapy, but in only 58% (P < .04) of those receiving no therapy. We conclude that children infected with Blastocystis often experience gastrointestinal symptoms and that treatment increases the rate of symptomatic improvement. We speculate that Blastocystis is a human pathogen.

Gastrointestinal syndromes associated with food sensitivity.

A wide range of clinical syndromes exist that are related to adverse reactions to dietary proteins and that affect predominantly the gastrointestinal tract of infants and children. Experimental data suggest a critical role for developmental alterations affecting intestinal permeability and the mucosal immune response that predispose to these conditions. The diagnostic and therapeutic approach to these disorders varies depending on the nature of the presumed offending antigen, the anatomic site affected, the severity of the inflammatory process, and the implications for future dietary and medical management. Ultimately, the proof that a particular dietary antigen is responsible is dependent on observing the response to oral challenge.

Initial evidence for sex-specific effects of early emotional abuse on affective processing in bipolar disorder.

PURPOSE: This study investigates the effect of sex and childhood trauma on affective processing in bipolar disorder (BPD) patients. METHODS: In a sample of fifty-six BPD patients, we administered the Childhood Trauma Questionnaire (CTQ), and the Iowa Gambling Task (IGT) and the Affective Go/No-Go (AGNG) to measure affective processing. Analysis of Variance (ANOVA) was used to evaluate the effect of sex and childhood trauma on IGT; Repeated-Measures ANOVAs to measure accuracy and bias measures across conditions on the AGNG. RESULTS: In the context of childhood abuse, females evidenced a more conservative cognitive style than males by selecting fewer cards from the disadvantageous decks [F(1, 49)=14.218; P<0.001] and showed an improvement throughout the task, as noted in a normal learning curve [F(1.49)=4.385; P=0.041)]. For the AGNG, an interaction specific to the negative valence stimuli on response bias measures was found. Abused females scored higher (mean=8.38; SD=6.39) than abused males (mean=0.69; SD=1.19) [F(1.46)=6.348; P=0.015]. CONCLUSION: Severity of childhood trauma was significantly different between sexes. In the context of a history of emotional abuse, male bipolar patients tended toward a more risk-taking behavior compared to female. Further investigations are needed to elucidate potential pathophysiological mechanisms underlying this interaction.

Fixing the intestinal mucosa in the bone marrow transplant patient: lessons from other intestinal immunodeficiencies and inflammatory disorders.

Gastrointestinal inflammation is common following bone marrow transplantation. Key pathogenetic events, such as major histocompatibility complex (MHC) expression on intestinal epithelial cells and local production of cytokines in the gastrointestinal mucosa, are common features of many gastrointestinal inflammatory disorders. Drawing from clinical experience of the treatment of other disorders associated with gastrointestinal inflammation, such as ulcerative colitis and Crohn's disease, a number of therapeutic alternatives may be relevant for the bone marrow transplant patient with significant graft-vs.-host disease (GvHD). Options to consider include therapeutics that alter inflammatory cell migration, anti-inflammatory cytokines, direct neutralization of proinflammatory cytokines, and cytokines that promote epithelial restitution in the gastrointestinal mucosa. In addition, a variety of nutritional and other novel treatments are available, which may improve epithelial function or which have anti-inflammatory actions. Prospective studies of combined nutrient and cytokine-modulating treatments for the bone marrow transplant patient are warranted.

Soluble interleukin-2 receptor as a marker of lymphocyte activation in childhood Crohn's disease.

Serum concentrations of the soluble form of the interleukin-2 receptor (sIL-2R) were determined by an enzyme-linked immunosorbent assay in a group of 39 pediatric and adolescent patients with Crohn's disease and in age-matched ulcerative colitis patients and controls. sIL-2R levels were found to be elevated in patients with Crohn's disease (p less than 0.001), and increased sIL-2R levels were detected in patients with clinically more severe disease. sIL-2R levels correlated more closely with other laboratory markers of disease activity than with a disease activity score. A progressive increase in sIL-2R levels was noted to correlate with endoscopic measurement of disease extent, while sIL-2R levels did not correlate with other markers of systemic lymphocyte activation, suggesting possible local mucosal production. Sequential determinations in individual patients revealed a good correlation between sIL-2R and clinical course. More important, elevated levels of sIL-2R preceded clinical relapse of asymptomatic patients. We conclude that sIL-2R measurement may be a useful adjunct to clinical assessment and routine laboratory testing in pediatric and adolescent patients with Crohn's disease and that serial levels may be predictive of clinical course and the response to therapy.

Patient and procedure variables associated with complications following variceal sclerotherapy in children.

Variceal sclerotherapy has been performed in the pediatric population, but techniques and dosages of sclerosant recommended in the literature are largely empirical. Having accumulated much data through experience with sclerotherapy in children, we have identified patient and procedure variables associated with early and late complications. We reviewed our experience with 37 pediatric patients, ages 1-18, who underwent 150 sclerotherapy sessions. Sclerotherapy was associated with 12 early complications in 11 patients. Early complications were bleeding (five), respiratory problems (three), false channel formation (two), and gross hematuria (two). Four patients developed strictures. We identified the following variables associated with complications: for bleeding, platelet count less than 100,000/mm3; for respiratory complications and false channel formation, weight less than 12 kg; for false channel formation, dosage of sclerosant/kg/session greater than 1.75 ml/kg; for gross hematuria, total sclerosant/session greater than 20 ml. A need for more than six sclerotherapy sessions for obliteration of varices was associated with a greater frequency of stricture formation. Sclerotherapy can be performed safely in children. Patients less than 12 kg or with platelet counts less than 100,000/mm3 should be monitored carefully for respiratory complications and postprocedure bleeding. Sclerosant dosages greater than 1.75 ml/kg, or 20 ml total sclerosant, should be given with caution.

Synergistic effects of interferon gamma and tumour necrosis factor alpha on T84 cell function.

BACKGROUND: Inflammatory bowel disease (IBD) is characterised by chronic intestinal inflammation and increased epithelial permeability. Both tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) have been implicated in IBD. AIMS: To understand better the effects of these cytokines on epithelial cell function. METHODS: T84 cells were cultured with IFN-gamma and TNF-alpha and changes in transepithelial resistance (TER), fluorescein isothiocyanate (FITC) dextran flux, short circuit current (I(sc)), cystic fibrosis transmembrane conductance regulator (CFTR) protein levels, cell morphology, TNF receptor gene expression, and apoptosis were assayed. RESULTS: Relative to controls, significant changes (p<0.05) occurred in cells incubated with IFN-gamma for two days: TER was decreased to 20 (6.2)%, FITC-dextran flux was increased by 109 (19)-fold, cAMP and Ca dependent I(sc) were decreased to 51 (6.4)% and 24 (2.2)%, respectively, and CFTR levels were decreased to 47 (11)%. Cell morphology was altered but cell death was not induced. TNF receptor mRNA levels were increased. When added with IFN-gamma, TNF-alpha accelerated IFN-gamma dependent changes. Relative to controls, significant changes occurred after one day of culture with IFN-gamma plus TNF-alpha: TER was decreased to 27 (3.5)%, FITC-dextran flux was increased by 185 (45)-fold, and cAMP and Ca dependent I(sc) were decreased to 66 (12)% and 35 (6.8)%, respectively. TNF-alpha also enhanced IFN-gamma dependent changes in cell morphology but did not induce cell death. CONCLUSION: IFN-gamma alters T84 cell epithelial properties and TNF-alpha can enhance these effects, perhaps due to IFN-gamma dependent increases in TNF receptor gene expression. Overall, these studies suggest that in IBD, TNF-alpha may have synergistic effects on IFN-gamma mediated alterations of epithelial cell function.

Acute Hepatitis.

The acute onset of hepatitis may occur in adolescents as a result of hepatic damage from infectious agents, drugs, or toxins, or it may be the initial presentation of a chronic autoimmune or metabolic liver disease. The authors characterize the clinical features of each of these disorders emphasizing recognition and diagnosis.

Gross hematuria following sclerotherapy of esophageal varices in patients with cystic fibrosis.

We report two patients with portal hypertension secondary to cystic fibrosis who developed transient gross hematuria following injection sclerotherapy of esophageal varices. Both patients developed this complication within 6 h of sclerosing sessions during which sodium morrhuate was used. Each cleared her hematuria within 4 days without developing oliguric renal insufficiency. Subsequent sclerotherapy was associated with no untoward effects. These are the only two pediatric patients among 40 whose varices we have sclerosed who have developed gross hematuria at the time of sclerotherapy, and they are our only two patients undergoing sclerotherapy who have had cystic fibrosis. The factors rendering them vulnerable to renal or urinary tract insult in the absence of other systemic complications are unclear. However, the therapeutic endoscopist should be cognizant of this potential adverse reaction when performing sclerotherapy.

The Santmyer swallow: a new and useful infant reflex.

A puff of air administered to the face of 102 subjects (from 33 week's gestation on the first day of life to age 42 years) elicited a reflex swallow identical to a normal primary peristaltic sequence in 88. Subjects who responded were younger than 24 months of age or severely disabled neurologically; those who did not respond were older than 11 months and free of neurological abnormality. Response was variable between 11 and 24 months. This swallow response appears to be a clinically useful but previously unrecognised infant reflex.

Novel primitive swallowing reflex: facial receptor distribution and stimulus characteristics.

We recently described a primitive swallowing reflex: swallowing as a response to a puff of air administered to the face. To identify the facial afferent distribution of this response, the necessary characteristics of the stimulus, and the role of the infant's antecedent behavior, we studied 13 infants who had demonstrated this reflex. We evaluated nine infants by clinically observing for swallowing in response to a total of 135 stimulus applications. All nine had consistently positive responses to the maxillary-ophthalmic area and to the maxillary-mandibular area. Two had consistent responses to stimulation of the mandibular area alone; these were positive. Six had consistent responses to stimulation of the ophthalmic area alone; these were negative. Four infants, evaluated by manometric documentation of swallowing (a total of 137 stimulus applications) demonstrated 47 of 79 (59%) positive responses to stimuli applied to facial areas including any parts of the lips, but only 7 of 28 (25%) positive responses to stimuli applied to facial areas excluding all parts of the lips (chi-square P = 0.002). Light touch to any facial area, including the cornea, failed to produce a swallow in any infant. Crying and sleep were incompatible with the reflex. This newly identified primitive swallow reflex seems to require diffuse stimulation, possibly thermal, to the perioral area of the face in an awake and noncrying infant.

Idiopathic hypereosinophilic syndrome terminating in acute lymphoblastic leukemia.

Idiopathic hypereosinophilic syndrome (IHES) is a heterogeneous group of disorders characterized by multisystem dysfunction and persistent, extreme eosinophilia of unknown cause. We describe a 9-1/2-year-old boy whose course included several unusual clinical features and terminated 2 years after diagnosis in acute lymphoblastic leukemia (ALL). Serial studies suggest that leukemia was not present earlier in his course. We speculate that this child may have had an evolving lymphoproliferative syndrome with a terminal blast crisis to which the eosinophilia was a nonmalignant leukemoid reaction.

Isolated pancreatic amylase deficiency: probable error in maturation.

A boy with failure to thrive and isolated pancreatic amylase deficiency is described. Immunoprecipitation confirmed only salivary isoamylase in duodenal fluid at ages 20 and 33 months. Because normal pancreatic amylase messenger RNA was detected by reverse-transcriptase polymerase chain reaction in the fluid, failure of the normal maturation of pancreatic amylase secretion may explain the deficiency.

Soluble interleukin-2 receptor as a predictor of neonatal sepsis.

We prospectively measured soluble interleukin-2 receptor levels in 56 premature infants with suspected sepsis and demonstrated significant differences between those with positive results on blood, urine, or cerebrospinal fluid cultures, and those with negative results. Soluble interleukin-2 receptor levels can be used to facilitate the diagnosis of sepsis in premature infants with negative blood culture results.

Symptomatic Helicobacter pylori infection in young patients with severe neurologic impairment.

Helicobacter pylori infection was identified in five patients with profound neurologic impairment who were undergoing evaluation for gastrointestinal symptoms, and it was subsequently identified in 7 of 61 patients with symptoms whose condition was evaluated prospectively. Institutionalized patients were at greater risk of infection. Treatment of H. pylori infection resulted in symptomatic improvement for the majority of patients.