Objectives: T cells play a crucial role in many chronic inflammatory diseases. Mucosal T cells are particularly important in the pathogenesis of Crohn’s disease (CD). We investigated the response of T cells in CD and other intestinal inflammatory conditions to interleukin-2 (IL-2), a cytokine essential for T-cell activation, growth, and function. Study design: T-cell reactivity was assessed by measuring growth induced by IL-2 in mucosal endoscopic biopsy specimens obtained from children with CD, ulcerative colitis, indeterminate colitis, and chronic nonspecific colitis and from children without gastrointestinal inflammation. Results: CD mucosal T cells grew remarkably and significantly more than T cells from normal, ulcerative colitis, and chronic nonspecific colitis mucosa. T cells from indeterminate colitis mucosa grew similarly to those of CD mucosa. The enhanced growth response in CD was independent of disease location, presence or absence of intestinal inflammation, treatment, disease duration, or clinical activity. Conclusion: Mucosal T cells from children with CD exhibit an intrinsic hyperreactivity to IL-2. This may represent a primary pathogenic abnormality in this condition. (J Pediatr 1998;133:675-81)

Byler disease (ByD) is an autosomal recessive disorder in which cholestasis of onset in infancy leads to hepatic fibrosis and death. Children who have a clinically similar disorder, but are not members of the Amish kindred in which ByD was described, are said to have Byler syndrome (ByS). Controversy exists as to whether ByD and ByS (subtypes of progressive familial intrahepatic cholestasis [PFIC]) represent one clinicopathological entity. The gene for ByD has been mapped to a 19-cM region of 18q21-q22. PFIC caused by a lesion in this region, including ByD, can be designated PFIC-1. Examination of haplotypes in siblings with ByS in two unrelated non-Amish families showed that the gene(s) responsible for their disorder(s) did not lie in the PFIC-1 candidate region. On light microscopy and transmission electron microscopy (TEM), liver tissue differed between Amish children with PFIC-1, who had coarsely granular bile and at presentation had bland intracanalicular cholestasis, and the children with ByS in the two non-Amish families, who had amorphous or finely filamentous bile and at presentation had neonatal hepatitis. Bile acid composition of bile also differed: In the Amish children with PFIC-1 and in one ByS family, the proportional concentration of chenodeoxycholic acid (CDCA) in bile was low compared with normal bile; in the other ByS family, it was only slightly reduced. Genetic analysis and light microscopy and TEM of liver may help distinguish PFIC-1 from other forms of ByS.

We performed percutaneous liver biopsy in nine children who had received a weekly dose of methotrexate, 10 mg/m2 per week, for at least 3 years to address the concern about subclinical liver toxicity from single, weekly, low-dose methotrexate therapy for juvenile rheumatoid arthritis. No patient had clinical or biochemical evidence of liver injury. All biopsy results were interpreted as normal. These results suggest that the recommendations of the American College of Rheumatology for adults receiving single weekly methotrexate therapy for rheumatoid arthritis can be extended to children.

The treatment of children with apparent ureteropelvic junction obstruction is controversial. In an asymptomatic infant or child the decision to recommend pyeloplasty usually is based on interpretation of the renal scan. We retrospectively analyzed the renal biopsy obtained during pyeloplasty in 55 children. Histological changes were compared to the differential renal function revealed on the preoperative renal scan. Histological changes were graded on a scale of I to V; I--normal, II--mild dilatation of the collecting tubules or Bowman's space and III to V--progressively severe changes of obstructive uropathy, including reduced glomerular number, glomerular hyalinization, cortical cysts and interstitial inflammation. Patient age ranged from 4 days to 19 years (mean 4.8 years). Mean differential function according to histological grade was I--49%, II--43%, III--42%, IV--30% and V--25%. Of 33 patients with a differential function of 40% or greater 26 (79%) had a grade I or II biopsy, while 21% had a more significant alteration in renal histology. In contrast when the differential function was less than 40% 6 of 18 patients (33%) had grade I or II disease on biopsy. In conclusion, in approximately 25% of children with ureteropelvic junction obstruction there is a disparity between preoperative differential renal function computed during diuretic renography and renal biopsy.

Children who undergo bilateral orchiopexy often have oligospermia or azoospermia in adulthood. This subfertility generally has been attributed to histological alterations in the cryptorchid testis. However, the possibility that an iatrogenic factor, such as mobilization of the vas deferens during orchiopexy, may have an adverse effect on fertility has not been studied. Six groups of mature Sprague-Dawley rats underwent right orchiectomy and the following procedures on the left side: group 1--sham operation, group 2--2 cm. of vas mobilized, group 3--4 cm. of vas mobilized, group 4--2 cm. of vas mobilized and deferential artery stripped off of vas, group 5--4 cm. of vas mobilized and deferential artery stripped off of vas and group 6--vasectomy. Each rat was then housed with 2 female rats for 24 days. Mobilization of the vas with disruption of the mesentery resulted in slight but statistically insignificant reduction in fertility. However, when the deferential artery was dissected off the vas, there was a marked reduction in fertility and fecundity. Histologically the vasa were normal without evidence of ischemic necrosis. The testes in groups 2 to 5 showed variable depletion of germ cells with shedding of germinal epithelium, and the testes and epididymides in group 5 were similar to the changes seen in vasectomized rats (group 6). No testes were necrotic. These data suggest that extensive mobilization of the vas causes subfertility in this animal model and may be secondary to a functional obstruction resulting from vas denervation. Whether a similar effect occurs during orchiopexy in humans deserves study.

We reviewed pathology specimens from 84 patients seen during a 10-year period with neonatal necrotizing enterocolitis, and these findings were correlated with clinical features. Coagulation (ischemic) necrosis, inflammation, and bacterial overgrowth were all present in the intestine of nearly all patients but with individual variability in the severity of these findings. Overall, coagulation necrosis was more severe than any other finding in most infants, indicating the importance of ischemia in the pathophysiology of necrotizing enterocolitis. Reparative tissue changes such as epithelial regeneration, granulation tissue formation, and fibrosis, found in two thirds of cases, suggested ongoing tissue injury of at least several days' duration. Birth weight, Apgar score, age, feeding status, and the presence of respiratory distress syndrome were not correlated with any particular histologic feature. The pathologic changes of necrotizing enterocolitis suggest that its cause is multifactorial, with ischemia, inflammation, bacterial overgrowth, and reparative tissue changes all playing important roles.

Enlarged gastric folds in pediatric patients are uncommon. Fifteen patients with upper gastrointestinal (GI) tract symptoms of chronic epigastric abdominal pain, vomiting, or hematemesis underwent radiologic upper GI barium studies and were found to have Campylobacter pylori gastritis at endoscopic biopsy. Seven patients (47%) with C pylori gastric disease had radiologic evidence of enlarged folds. There was no clinical or pathologic evidence of Ménétrier disease. Therefore, C pylori gastritis should be considered in the differential diagnosis of children with upper GI tract symptoms and radiologic evidence of enlarged folds.

Barrett's esophagus, a columnar metaplasia of the lower esophagus that is usually associated with gastroesophageal reflux (GER), was found in three children on long-term antileukemia chemotherapy. Two of the children had been on a standard acute lymphoblastic leukemia (ALL) maintenance protocol with 2 to 3 years of methotrexate and 6-mercaptopurine administration. The third child received daunorubicin, cytosine arabinoside, and 6-thioguanine for treatment of acute myelogenous leukemia (AML). None of the patients had clinical or pathologic evidence of GER disease. We propose that the Barrett's esophagus in these patients did not result from the usual peptic esophagitis, but rather from chemotherapy-induced esophageal mucosal injury.

Systemic infection with Malassezia furfur was first reported in 1981 as a specific complication of Intralipid therapy in a neonate. Six additional patients, including three older than 16 years of age, were identified subsequently. All had received prolonged Intralipid infusion through central venous catheters. Pulmonary infection was documented in tissue in three cases, the clinical presentation was characterized by pulmonary infiltrates, fever, and, in the infants, thrombocytopenia. Two subgroups of patients appear to be at the greatest risk for Malassezia infection: neonates with cardiopulmonary disease and adults with severe gastrointestinal disease and immunosuppression. The documentation of pulmonary arterial lipid deposits in vessels that had been infiltrated by Malassezia organisms and the observation of organisms in small pulmonary thromboemboli suggest that these lipophilic and lipid-dependent organisms are introduced into the bloodstream from venous catheters and require high lipid concentrations to proliferate in tissue.

A 6-month-old infant presenting with pericardial effusion was found to have a malignant rhabdoid tumor of the heart. As visualized by two-dimensional echocardiography and subsequently by contrast-enhanced computerized axial tomographic scanning, the tumor arose from the left ventricular free wall and grew into the pericardial space. Despite two courses of single-agent chemotherapy with doxorubicin, the child died 3 months later. This is the first reported case of malignant rhabdoid tumor of the heart, and the fifth case of a primary cardiac malignancy in an infant.

Fresh isolated myocardial, elastic-arterial, and valvular tissues from seven canine hearts were irradiated by argon laser. Irradiation was transmitted through 300 and 400 μm flexible quartz fiberoptic elements. Minimal power densities for vaporization of the myocardial, arterial, and valvular tissues were 80, 90, and 110 W/cm2, respectively, with maximal vaporization distances (fiberoptic tip to tissue) of 4 mm, 1 mm, and 1 mm, respectively. Irradiation of the valves at power densities approaching perforation caused contraction of the tissue. When tissue vaporization occurred, histologic examination of irradiated tissues showed a central crater surrounded by sequential layers of char, vaporization, and coagulation necrosis. These findings were common to all cardiac tissues. Additional findings unique to myocardium were a normal-appearing myocardial layer (skip-area), circumferential halo, and tissue clefts. Elastic arteries showed concentration of necrosis around the collagen and elastic fibers. Valvular damage was the most extensive and also included contraction of adjacent valvular tissue and endocardial sloughing.

Torulopsis glabrata causes an increasingly frequent infection in immunocompromised adults. In a 1,910-g, 36-week, small-for-gestational-age neonate, T glabrata caused necrotizing enterocolitis and endophthalmitis. The fungus was not grown from cultures obtained from four blood specimens but was seen microscopically in methenamine silver-stained sections of resected bowel.