Lynn Duffy

Neuronal intestinal dysplasia : quantitative diagnostic criteria and clinical management

Neuronal intestinal dysplasia (NID) clinically resembles Hirschsprungs disease but is characterized by hyperplasia rather than aganglionosis of the intramural plexus. Surgical intervention is common. We report the 5-year follow-up of an infant with the mixed form of NID managed medically and a method by which NID can be quantified historically. Hyperganglionosis was determined by counting the number of ganglia per high-power field and the number of ganglion cells per ganglia from at least two biopsy specimens. The patients biopsies and biopsies from “normal” and “inflamed” patients were compared. Normals contained 0.68 ± 0.28 (X ± SD) ganglia per high-power field and 2.16 ± 0.31 ganglion cells per ganglion. The inflamed biopsies were similar, 0.69 ± 0.38 ganglia per high-power field and 2.63 ± 0.40 ganglion cells per ganglion. The patients initial rectal biopsy revealed 7.6 ganglia per high-power field and 3.8 ganglion cells per ganglion. Management of the patient included saline colonic irrigations and hyperalimentation with gradual reinstitution of breast-feeding. Clinical improvement was associated with normalization of manometry and biopsy findings, a phenomenon not documented previously in the literature. Irrigations were stopped at age 9 months, and the child is now asymptomatic.

Ethanol and fetal nutrition: effect of chronic ethanol exposure on rat placental growth and membrane-associated folic acid receptor binding activity

Summary Rat placental composition and specific folate receptor activity were measured at 20 days gestation in dams exposed to chronic high doses of ethanol (6%, vol/vol) throughout gestation and in isocalorically pair fed controls. Ethanol exposed fetuses were smaller (ethanol = 3.28 ± 0.08 vs. control = 4.01 ± 0.10 g, p < 0.001), but their placentae were larger (experimental = 0.534 ± 0.02 vs. control = 0.399 ± 0.01 g, p < 0.001). The increased weight appears to be secondary to hyperplasia as total DNA was increased while the wet/dry, RNA/DNA, and protein/ DNA ratios were not different. Despite larger placentae, specific folate receptor activity was significantly reduced in the ethanol exposed tissue, whether expressed relative to membrane protein, placental weight, or total placental binding. These results confirm that ethanol exposure is placen totoxic and suggest an additional mechanism by which ethanol may lead to intrauterine growth retardation; namely, decreased folate receptor activity.

Hepatitis in children with acquired immune deficiency syndrome

Hepatic morphology and immunocytology were evaluated in 4 children with clinical and immunologic characteristics of the acquired immune deficiency syndrome or acquired immune deficiency syndrome related complex. All 4 children had hepatomegaly and increased serum alanine and aspartate aminotransferase activity. Both lobular and portal changes were noted. Lymphocytic infiltration, piecemeal necrosis, hepatocellular and bile duct damage, sinusoidal cell hyperplasia, and endothelialitis were prominent. Vesicular rosettes in sinusoidal lymphocytes and tubuloreticular structures in sinusoidal endothelial cells were demonstrated by electron microscopy. The lymphocytic infiltrate in both the lobular and portal spaces was characterized by a relative increase of cytotoxic/suppressor (T8) cells. Hepatitis may be a common feature of pediatric acquired immune deficiency syndrome and acquired immune deficiency syndrome-related complex. Although the histopathologic changes are consistent with chronic active hepatitis, the specific pathogenesis remains to be determined.

Infliximab-induced psoriasis in children with inflammatory bowel disease.

Infliximab is frequently used to treat both inflammatory bowel disease (IBD) and psoriasis. We reviewed the medical records of 73 children with IBD receiving infliximab therapy and identified 6 (8%) cases of infliximab-induced psoriasis. Five (83%) had Crohn disease and 4 (67%) were girls. The psoriatic lesions appeared on the face (n = 5; 83%) and perineum (n = 1; 17%). A median of 13 doses were administered during a median duration of 21 months. All of the patients were continued on infliximab to maintain clinical remission of IBD. Educating children with IBD and their caregivers about this paradoxical phenomenon and periodic dermatology evaluation may promote patient care.

Hepatic Na,K-ATPase development in the rat

The development of the enzyme Na,K-ATPase was studied in hepatic tissue from Sprague-Dawley rats at 18-20 days of gestation, 1, 3, 5, 7, 14, 21, and 30 days, and young adulthood (45 days). A developmental pattern was demonstrated for total and membrane-associated Na,K-ATPase activity. The activity in tissue homogenate, expressed per gram tissue, increased from late fetal life, 43.4 +/- 1.3 mumol Pi g liver-1 h-1, until 21 days of age, when an adult level of 187.3 +/- 19.6 mumol Pi g liver-1 h-1 was attained. A less pronounced ontogenic pattern was observed when enzyme levels were expressed as specific activity per milligram protein. The activity profile in a crude membrane preparation was similar. The potential for stimulation of enzyme activity by glucocorticoids was studied in 11-day-old animals injected with cortisone acetate (10 mg 100 g body weight-1) for 3 days. Enzyme specific activity was inducible: Specific activity was greater in cortisone-treated animals, 1.794 +/- .043 mumol Pi mg protein-1 h-1, versus controls, 1.258 +/- 0.043 mumol Pi mg protein-1 h-1 (p less than 0.01). We postulate that this developmental pattern for hepatic Na,K-ATPase activity may be a reflection of, or a contributing factor in, the ontogeny of sodium-dependent hepatic transport, such as that for bile salts.

Sulfasalazine and renal tubular function: lack of an effect.

Sulfasalazine (SASP) is frequently used in the treatment of chronic inflammatory bowel disease (IBD), particularly colitis. Because the drug poses a theoretical risk for renal tubular damage, 26 patients, 8–18 years of age, with Crohns ileocolitis were studied. Thirteen children were receiving SASP while 13 served as disease controls. Renal tubular function was assessed by measurement of urinary β2-microglobulin and n-acetylglucosa-minidase activity. No abnormalities were found on routine measurement of renal function. Similarly, urinary β2-microglobulin and n-acetylglucosaminidase activities were within normal limits for patients receiving SASP, as well as for disease controls. Although there is a theoretical risk for renal tubular damage from the prolonged use of SASP, this study would suggest that IBD patients receiving the drug are at no greater risk for renal injury than their counterparts not receiving the medication.

151 Improved Outcomes in a Quality Improvement Collaborative for Pediatric Ulcerative Colitis

Aim: 30% of patients hospitalized with severe UC prove steroid-refractory. We aimed to evaluate outcomes and predictors of response to infliximab as rescue therapy in severe pediatric UC. Methods: As part of a prospective multicenter study, we evaluated factors associated with immediate and 1-year response to infliximab in steroid-refractory severe pediatric UC. Data were recorded at admission, days 3 and 5, at introduction of infliximab, at discharge and 1-year thereafter, using standardized data collection forms. Disease activity was determined using the validated Pediatric UC Activity Index (PUCAI). Serum TNF alpha level was determined before infliximab treatment using a cytokine antibody panel (TransSignal, CA). Concurrently, fecal calprotectin and lactoferrin levels were ascertained using standard assays in a central laboratory. Results: Of 128 children admitted, 33 failed steroids and treated with infliximab within 10.5±6 days. Mean PUCAI score at introduction of infliximab was 66±13 points, indicating persistence of severe colitis. 25/33 children (76%) responded and were discharged within 5±4 days of infliximab therapy; 7 in complete clinical remission (PUCAI 0.2). CRP, ESR, albumin and hemoglobin were not predictive of response to infliximab. Neither fecal calprotectin nor lactoferrin values were predictive of response (area under ROC curve 0.61 and 0.63, respectively; P>0.2). Serum TNF-alpha level was similar between responders and non-responders (10.6pg/ml (IQR 4-30) vs. 8.3pg/ml (5.7-11); P=0.4). 8 of the 25 responders received only 3-dose induction, and the others continued maintenance therapy without concomitant immunomodulation. Cumulative 1-year sustained response rate was 55% (18/33). There were no deaths and only 1 patient stopped treatment due to infusion reaction. Conclusion: Infliximab is safe and effective in inducing and maintaining clinical remission in steroid-refractory pediatric UC. Serum TNF-alpha level and fecal biomarkers are not useful in predicting outcome, but higher disease severity, judged clinically, and new onset disease are associated with reduced response.