Delayed contrast enhancement magnetic resonance imaging in congenital aortic stenosis.

We report a case of a 12-year-old boy with severe congenital aortic stenosis in whom magnetic resonance imaging (MRI) with delayed contrast enhancement demonstrated extensive subendocardial hyperenhancement within the left ventricle. The hyperenhancement was confirmed to be subendocardial infarct and fibrosis by histopathology. This case supports the utility of MRI with delayed contrast enhancement in evaluating myocardial viability in patients with congenital heart disease.

Pulmonary atresia with intact ventricular septum, right-sided aortic arch and ventriculocoronary connection--prenatal echocardiographic diagnosis.

The authors describe the prenatal echocardiographic diagnosis of a rare case of pulmonary atresia with intact ventricular septum, right-sided aortic arch, and ventriculocoronary connection in a fetus at 21 weeks gestation. The diagnosis was confirmed at autopsy.

Intrinsic hyperreactivity of mucosal T cells to interleukin-2 in pediatric Crohn's disease.

OBJECTIVES: To 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.

Genetic and morphological findings in progressive familial intrahepatic cholestasis (Byler disease [PFIC-1] and Byler syndrome): evidence for heterogeneity.

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.

Liver biopsy findings in patients with juvenile rheumatoid arthritis receiving long-term, weekly methotrexate therapy.

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.

Renal histological changes secondary to ureteropelvic junction obstruction.

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.

Influence of vas deferens mobilization on rat fertility: implications regarding orchiopexy.

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.

Morphometric analysis of the lung in bronchopulmonary dysplasia.

We studied lung development in children with or without bronchopulmonary dysplasia (BPD) using light microscopic morphometry and thick lung sections stained for elastic fibers. One lung was obtained at autopsy from each of eight patients with BPD (ages, 2 to 28 months) and six children (ages, 5 days to 51 months) who died without lung disease. Patients with BPD demonstrated severe somatic growth retardation and had reduced lung volumes with abnormal lobar volume proportions. In the central bronchi mean volume proportion of glands and smooth muscle was increased in BPD. Bronchiolar density was also increased, but it tended to normalize with advancing age. Mean bronchiolar diameter was slightly smaller in BPD, and bronchiolar smooth muscle hypertrophy was a constant histologic feature. The most striking change, however, was noted in alveolar structure and development. Total alveolar number was severely decreased in patients with BPD compared with that in control subjects, and there was little evidence of compensatory alveolar development with increasing age. Lung internal surface area was correspondingly reduced, and mean linear intercept was increased. Sections stained for elastic tissue demonstrated in the patients with BPD a simplified acinar structure with thickened, tortuous, and irregularly distributed alveolar elastic fibers. We conclude that in severe, fatal BPD there is marked impairment of lung development with alveolar hypoplasia and reduced internal surface area. In addition, bronchial and bronchiolar smooth muscle hypertrophy and bronchial gland hyperplasia may be important contributing factors to airflow limitation.

Pathology of neonatal necrotizing enterocolitis: a ten-year experience.

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 association with Campylobacter pylori gastritis.

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.

Campylobacter pylori--associated gastritis and peptic ulcer disease in children.

Specimens obtained at gastric biopsies performed for suspected acid peptic disease in patients 5 through 17 years of age were retrospectively reviewed for the presence of Campylobacter pylori (CP), a gram-negative bacillus associated with chronic gastritis and peptic ulcer disease in adults. Of 98 patients who underwent antral biopsy (the most reliably colonized site in the stomach), 40 had chronic gastritis histologically. Of those 40 patients, 22 (55%) had CP present on the gastric surface. None of the 58 patients without gastritis present in biopsy specimens had CP. The gastritis in children with CP was more severe than in those without the organism: 86% of those with moderate gastritis and 92% of those with severe gastritis had CP. Eight patients with duodenal ulcers and one patient with a gastric ulcer had CP on biopsy. Among those patients without CP, only one had a duodenal ulcer and eight had gastric ulcers. An additional nine patients found to have CP on gastric fundic biopsy were identified, for a total of 31 patients with CP identified by either antral (22) or fundic (nine) biopsy. Initial resolution of symptoms with standard acid-antagonist therapy was noted in the 25 of 31 CP(+) patients so treated, but a high relapse rate was noted within one to two years in the patients who also had gastritis and duodenal ulcer. These findings support a strong association between CP colonization of the stomach and the presence of chronic gastritis and duodenal ulcer disease in children.

Barrett's esophagus in three children after antileukemia chemotherapy.

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.

Three conditions in neonatal asphyxiating thoracic dysplasia (Jeune) and short rib-polydactyly syndrome spectrum: a clinicopathologic study.

Clinicopathologic examination of eight patients with asphyxiating thoracic dysplasia (Jeune; ATD) disclosed two different types, which were designated as type 1 and type 2. Type 1 ATD was characterized by the presence of radiologically irregular metaphyseal ends and histopathologically irregular cartilage bone junction with patchy distribution of physeal zone of hypertrophy. Type 2 ATD showed radiologically smooth metaphyseal ends and histopathologically diffusely retarded and disorganized physes with smooth cartilage bone junctions. Examination of four patients with the "Verma-Naumoff" short rib-polydactyly syndrome showed many radiologic and pathologic features similar to those of type 1 ATD. Differential diagnosis of these three osteochondrodysplasias is discussed along with chondroectodermal dysplasia (Ellis-van Creveld), short rib-polydactyly syndrome type 1 (Saldino-Noonan), short rib-polydactyly syndrome type 2 (Majewski), and the new short rib syndrome reported by Beemer et al [1983].

Islets of Langerhans in adolescents and adults with cystic fibrosis. A quantitative study.

The incidence of fasting hyperglycemia and diabetes mellitus (DM) in older patients with cystic fibrosis (CF) is reported to be 8%, but few quantitative studies of the islets of Langerhans in this disease have been done. Three groups of patients were studied in this morphometric autopsy analysis: patients with CF and insulin-dependent DM (n = 7), normoglycemic patients with CF (n = 4), and age-matched adolescents and young-adult controls (n = 11). The islets of Langerhans were stained with immunoperoxidase for insulin, glucagon, and somatostatin. The percentage of the total islet surface area occupied by each immunoperoxidase positive cell type was determined by a point-counting method. The mean percent surface area occupied by insulin-producing cells (28.3%) in diabetics with CF was significantly less than normoglycemics with CF (46.7%) and controls (53.4%). The mean percent surface area occupied by glucagon-producing cells was similar in all three groups: 21.9% in CF diabetics, 25.4% in normoglycemics with CF, and 22.4% in controls. The mean percent surface area occupied by somatostatin was increased in both CF groups compared with controls: diabetics with CF, 29.3%; normoglycemics with CF, 26.2%; and controls, 15.5%. These findings correlate with published clinical endocrine studies of hyperglycemia in CF. Endocrine cell quantitation in diabetics with CF differs from that in both juvenile (type 1) and adult-onset (type 2) DM.