Ectopia of both moieties of ureteral duplication anomalies.

The upper pole ureter of a duplication anomaly can be orthotopic or associated with an ectopic insertion, a ureterocele, or even ureteropelvic junction obstruction. The lower pole ureter may terminate orthotopically or laterally on the trigone, resulting in varying grades of vesicoureteral reflux. It can also be associated with lower pole ureteropelvic junction obstruction. In this report, we describe 3 patients with ureteral duplication anomalies in whom both upper and lower ureters terminate ectopically outside the bladder. The mode of presentation, the diagnosis, and the management of this rare anomaly are described. In addition, a hypothesis is advanced to help understand the embryologic pathophysiology.

Pathology of corneal endothelium in keratoconus.

Keratoconus is characterized by stromal thinning and conical deformity of the cornea that affects a small but significant portion of the population. Although keratoconus has been well studied, endothelial changes have not been extensively investigated. We studied the endothelium of 14 keratoconus corneal buttons obtained over the past 6 years by penetrating keratoplasty using light microscopy, scanning electron microscopy and transmission electron microscopy. Observations were correlated with patient history. Corneas demonstrated: endothelial cell pleomorphism and polymegathism (6 corneas); endothelial cell degeneration (13), and evidence of anterior chamber inflammation (4). Patterns of endothelial damage were variable ranging from isolated cell membranolysis to denudement of Descemet's membrane. Less damage was present at the apex of the cones than that observed in a circumferential pattern at the bases. In general the damage observed correlated with the severity and duration of the keratoconus with 9 years being the dividing time between mild and severe endothelial cell damage. These observations support other studies that implicate contact lens wear as a cause of pleomorphism and polymegathism in these patients. Endothelial cell alterations are likely a secondary event occurring due to mechanical stresses.

Hydrogen peroxide stimulates rat colonic prostaglandin production and alters electrolyte transport.

The changes in short circuit current (electrogenic Cl- secretion) of rat colon brought about by xanthine/xanthine oxidase in the Ussing chamber were inhibited by catalase and diethyldithiocarbamate, but not by superoxide dismutase. These results, the reproduction of the response with glucose/glucose oxidase and with exogenous H2O2, and the lack of effect of preincubation with deferoxamine or thiourea implicate H2O2, and not O2- or OH., as the important reactive oxygen metabolite altering intestinal electrolyte transport. 1 mM H2O2 stimulated colonic PGE2 and PGI2 production 8- and 15-fold, respectively, inhibited neutral NaCl absorption, and stimulated biphasic electrogenic Cl secretion with little effect on enterocyte lactic dehydrogenase release, epithelial conductance, or histology. Cl- secretion was reduced by cyclooxygenase inhibition. Also, the Cl- secretion, but not the increase in prostaglandin production, was reduced by enteric nervous system blockade with tetrodotoxin, hexamethonium, or atropine. Thus, H2O2 appears to alter electrolyte transport by releasing prostaglandins that activate the enteric nervous system. The change in short circuit current in response to Iloprost, but not PGE2, was blocked by tetrodotoxin. Therefore, PGI2 may be the mediator of the H2O2 response. H2O2 produced in nontoxic concentrations in the inflamed gut could have significant physiologic effects on intestinal water and electrolyte transport.

Immune system control of rat and rabbit colonic electrolyte transport. Role of prostaglandins and enteric nervous system.

The role of the immune system in controlling intestinal electrolyte transport was studied in rat and rabbit colon in Ussing chambers. A phagocyte stimulus, the chemotactic peptide FMLP, and a mast cell stimulus, sheep anti-rat IgE, caused a brief (less than 10 min) increase in short-circuit current (Isc). Products of immune system activation, platelet-activating factor (PAF) and reactive oxygen species (ROS), caused a sustained, biphasic increase in the Isc. Ion replacement and flux studies indicated that these agonists stimulated electrogenic Cl secretion and inhibited neutral NaCl absorption; responses that were variably inhibited by the cyclooxygenase blockers indomethacin and piroxicam. Lesser degrees of inhibition by nordihydroguaiaretic acid could be accounted for by decreased prostaglandin synthesis rather than by lipoxygenase blockade. Tetrodotoxin, hexamethonium, and atropine also inhibited immune agonist-stimulated Isc, but had no effect on immune agonist-stimulated production of PGE2 or PGI2. These results indicate that immune system agonists alter intestinal epithelial electrolyte transport through release of cyclooxygenase products from cells in the lamina propria with at least 50% of the response being due to cyclooxygenase product activation of the enteric nervous system. The immune system, like the enteric nervous system and the endocrine system, may be a major regulating system for intestinal water and electrolyte transport in health and disease.