Apoptotic epithelial cells in biopsy specimens from infants with streaked rectal bleeding.

BACKGROUND: Histologic studies of rectosigmoidal mucosal biopsies of infants with isolated blood-streaked stool have shown many eosinophils and revealed aggregates of small dark granules (nuclear dust). However, no description of the nuclear dust has been made for this condition and the nature of the nuclear dust has not been thoroughly investigated. We determined the characteristics of these particles in biopsies from infants with streaked rectal bleeding. METHODS: Nineteen infants who were younger than 6 months old and had isolated rectal bleeding were studied, as were six age-matched control infants. Rectosigmoidal mucosal biopsies were immunohistochemically assessed using anticarcinoembryonic antigen and macrophage-associated antibodies and examined for apoptotic cells by modified in situ TdT-mediated dUTP-biotin nick-end labelling. The number of apoptotic epithelial cells was compared between rectal bleeding and control groups. RESULTS: Immunohistochemistry showed that at least some of the nuclear dust consisted of apoptotic epithelial cells. Infants with rectal bleeding also showed nodular lymphoid hyperplasia (n = 16), abundant eosinophils (>20/high power field, n = 14) in the mucosa, and a significantly high number of apoptotic epithelial cells relative to the control group. Rectal bleeding disappeared at 6-month follow-up in 14 of 18 infants (one was lost to follow-up) who were fed a different milk formula or breast-fed (their mothers were restricted from having cow's milk and eggs). CONCLUSIONS: The high number of apoptotic epithelial cells in rectosigmoidal mucosal biopsies of infants with streaked rectal bleeding is probably caused by accelerated epithelial cell turnover and apoptosis.

SLC7A7 genomic structure and novel variants in three Japanese lysinuric protein intolerance families.

Lysinuric protein intolerance (LPI) is a rare inherited disease caused by defective transport of the dibasic amino acids at the basolateral membranes of epithelial cells in the renal tubules and small intestine. The metabolic defect leads to brain dysfunction caused by hyperammonemia with a functional impairment of the urea cycle. Recently, mutations in the human SLC7A7 cDNA coding for y(+)LAT-1, which express dibasic amino acid transport activity, were reported to be responsible for LPI. In the present study, we examined the genomic structure of SLC7A7 by DNA sequencing of PCR products, and determined that the gene had 11 exons and 10 introns spanning about 18 kb of genomic DNA. We also identified an alternative RNA splicing at the 5' untranslated region of the SLC7A7 mRNA in human peripheral blood leukocytes, cultured lymphoblasts, and fibroblasts. As a result of mutational analysis of SLC7A7 in three Japanese LPI families, we found a nonsense mutation (R410X), a splicing mutation(911+1G>A) in intron 4, and four silent polymorphisms (201C/T, 445A/G, 784C/T, 946T/C). Identification of the genomic structure of SLC7A7 may provide a molecular basis for a genetic survey for LPI.

Tremor and seizures associated with chronic manganese intoxication.

Tremor and seizures developed in a 2-year-old girl receiving total parenteral nutrition. T1-weighted images on MRI revealed areas of hyperintensity in the basal ganglia, brainstem and cerebellum. Blood manganese was elevated. The symptoms and MRI abnormalities disappeared after withdrawal of manganese administration. The recommendation of daily parenteral manganese intake was discussed.

Idiopathic neonatal hepatitis presenting as neonatal hepatic siderosis and steatosis.

Idiopathic neonatal hepatitis (INH) is a heterogeneous disease of undetermined cause. We report a retrospective histologic reevaluation of INH. Sixty patients with INH were reviewed along with 32 biliary atresia (BA) patients. Histologic findings, iron and fat deposits, giant cell transformation, portal fibrosis, and bile duct proliferation were semiquantitatively graded from 0 to 4+. Significant histologic findings were defined as > or =2+. Frequencies of patients with significant histologic findings in the INH group were compared with those of the BA group. Among the patients with significant histologic findings, those in the INH group had significantly less iron deposits (P < 0.01), portal fibrosis (P < 0.01), and bile duct proliferation (P < 0.01) than those of the BA group. A combination of significant hepatic macrovesicular steatosis and siderosis was observed in 10 INH patients but not in any BA patient (10/60 vs 0/32, P < 0.05). Without extensive treatment, the 10 INH patients all recovered, and hepatic abnormalities normalized by the age of 12 months. In conclusion, the present study showed that the recognition of hepatic siderosis is helpful to distinguish BA from INH and that in a subset of INH patients hepatic macrovesicular steatosis and siderosis occurs.

Axial spondylometaphyseal dysplasia.

UNLABELLED: We present a previously undescribed skeletal dysplasia characterized by mild platyspondyly, small thorax with cupping of the anterior ends of the ribs, irregular proximal femoral metaphyses, and lacy appearance of the iliac wings. Two of the three cases were siblings. Retinitis pigmentosa and optic atrophy are associated findings. CONCLUSION: We describe a new type of spondylometaphyseal dysplasia (SMD) and propose the name axial SMD.

Intestinal IgA deposition in Henoch-Schönlein purpura with severe gastro-intestinal manifestations.

UNLABELLED: In patients with Henoch-Schönlein purpura (HSP) presenting with severe gastro-intestinal (GI) symptoms, IgA deposition was studied in endoscopically obtained mucosal biopsies. A total number of 11 patients (male, 7; female, 4) were enrolled in this study; 7 patients underwent upper GI endoscopy and biopsy 1 underwent sigmoidoscopy and 3 underwent both. Upper GI endoscopy in each patient showed various mucosal changes including redness, petechiae, erosions, and ulcerations, most predominant in the second part of the duodenum. Sigmoidoscopy demonstrated no abnormality in two of four patients. Intestinal deposition of IgA was positive in 7 of 11 patients with HSP. Histological examination showed non-specific inflammation of varying degrees in each patient, but no small vessel vasculitis was observed. IgA deposits were seen in only 2 of 23 control subjects with various GI diseases. Positive rate of IgA deposition per patient was significantly higher in patients with HSP than in controls (P < 0.005). CONCLUSION: IgA deposition in the GI tract, as in the skin and kidneys, is characteristic of HSP. Intestinal IgA deposition complements the diagnostic criteria of HSP.

Patent ductus venosus with hypoplastic right hepatoportal system in a young child born with asymmetric intra-uterine growth retardation.

We report a functioning ductus venosus with hypoplasia of the right hepatoportal system in a 2-year-old child born with asymmetric intra-uterine growth retardation. Postprandial galactosaemia and hyperammonaemia were clues to diagnosis of portal-systemic shunt through the patent ductus venosus, which was confirmed by ultrasonography and angiography.

[123I-IMP per-rectal portal scintigraphy in a patent ductus venosus: a case report].

Portosystemic shunt is most frequent in portal hypertension associated with hepatic cirrhosis, meanwhile there are uncommon cases which have congenital portosystemic shunt. Recently we have encountered a patient with ductus venosus definitely diagnosed by angiography. In this patient, we performed a portal scintigraphy with 123I-IMP per-rectal administration in order to evaluate the portosystemic circulation. At the early phase of the study, the scintigraphy showed only the pulmonary uptake of 123I-IMP, and the liver was not revealed. Such findings in congenital anomalous cases of portosystemic shunt without hepatic parenchymal damage like this case can be similar to those in cirrhotic patients. In conclusion, this method was useful in evaluation of the portosystemic circulation, and helpful in determining therapeutic procedures for portosystemic circulation disorders.