Duodenal gastric heterotopia: further evidence of an association with fundic gland polyps.

Duodenal gastric heterotopia (DGH) is a common incidental finding at endoscopy, generally assumed to be congenital in origin. A recent study has suggested a possible association with gastric fundal gland polyps (FGPs). In this review of 37 patients with histologically confirmed DGH, the background to our present understanding of the DGH lesion is reviewed, the clinical and pathological associations of the condition in our cohort are identified, and the histological and immunohistochemical features of the DGH lesion are described. An association with the presence of FGPs is again demonstrated, whereas an inverse relationship with Helicobacter pylori is also shown. Immunohistochemical staining demonstrates that the fundic-type glands of DGH express the proton pump antigen (H(+)K(+)ATPase), whereas the overlying surface mucosa expresses the mucin profile of normal gastric-type mucosa (mucin-5AC positive, mucin-2 negative). DGH may represent a further component of the iatrogenic hypergastrinemia-related hypothesis for FGP development, although further study is required to confirm this.

The absence of a mucosal lesion on standard histological examination does not exclude diagnosis of celiac disease.

Some patients with undiagnosed celiac disease have minor mucosal lesions that may not be apparent during routine histological analysis. Twenty-five such patients of our institution were discharged to their primary-care physicians despite having positive endomysial antibody serology. To re-evaluate diagnosis for these patients, immunohistological staining with antibodies to CD2, CD3, CD7, CD8, CD69, and Ki67 was conducted on original biopsies from twenty patients. Clinical, serological, and histological investigations were offered to all fourteen patients who attended for review. We observed a significantly greater (P < 0.0001) numbers of intraepithelial lymphocytes and Ki67-positive enterocytes in sections from these twenty patients than for normal controls. Of the fourteen patients who attended for further review, firm diagnosis of celiac disease was made for seven patients and diagnosis was likely for another two. Our study clearly revealed that over-reliance on standard histological findings results in failure to diagnose celiac disease.

Megacystis-microcolon-intestinal hypoperistalsis syndrome: evidence of intestinal myopathy.

We investigated small- and large-bowel specimens of three newborn infants presenting with the clinical and radiological symptoms of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS). Conventional histological staining revealed marked thinning of the longitudinal muscle layer. Electron-microscopic investigations showed typical "central core" vacuolic degeneration of smooth-muscle-cells combined with proliferation of col lagen fibres. The expression of alpha-smooth-muscle actin was absent or markedly reduced in the circular and longitudinal muscle layers and muscularis mucosae compared to the normal controls. These findings suggest that the intestinal obstruction in MMIHS is due to an abnormality of the smooth-muscle cells.

Upregulation of angiotensin II receptors in reflux nephropathy.

BACKGROUND/PURPOSE: Reflux nephropathy (RN) is the cause of end-stage renal failure in 3% to 25% of children and in 10% to 15% of adults. Angiotensin II (Ang II) is a biologically active peptide of the renin-angiotensin system (RAS), which has a profound role not only in the urinary tract-development, but also in the response of the urinary tract to injury. The actions of Ang II are mediated through 2 receptors, angiotensin type 1 receptor (AT(1)R) and angiotensin type 2 receptor (AT(2)R). The aim of this study was to examine the expression of AT(1)R and AT(2)R in severe reflux nephropathy. METHODS: The kidney specimens from 8 patients (age range, 6 months to 14 years) with severe reflux nephropathy secondary to primary high-grade vesicoureteral reflux (VUR) were obtained at the time of nephrectomy. Control material included normal kidney specimens obtained from 3 adult patients during partial nephrectomy for an incidentaloma. Soluble enzyme immunohistochemistry was carried out using polyclonal antibodies to AT(1)R and AT(2)R. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to evaluate the relative amount of AT(1)R and AT(2)R mRNA. RESULTS: In the refluxing kidney there was strong AT(1)R immunoreactivity in the glomerulus and proximal tubules and moderate to weak immunoreactivity in the distal tubules. There was strong AT(2)R immunoreactivity in the distal tubules with absent or weak staining in the glomerulus and proximal tubules. In the control kidneys, homogeneous weak AT(1)R immunoreactivity was shown in the proximal and AT(2)R in the distal tubules, respectively. RT-PCR showed strong AT(1)R and AT(2)R expression in the refluxing kidneys compared with controls. CONCLUSIONS: Upregulation of angiotensin II receptors in reflux nephropathy suggests that Ang II is involved in the pathogenesis of the renal parenchymal damage in patients with RN. Pharmacologic blockade of angiotensin II receptors may be helpful in preventing renal fibrosis associated with reflux nephropathy.