NSAID-induced pyloric stenosis leading to oesophageal intramucosal dissection.

We describe a rare case of a 75-year-old woman with significant non-steroidal anti-inflammatory drug (NSAID) use who presented with haematemesis. Upper endoscopy revealed a large (9 cm) intramucosal dissection of the oesophagus without extension into the gastro-oesophageal junction and a severely narrowed pylorus. We postulate that she developed pyloric stenosis due to peptic ulcer disease from chronic NSAID use. This then led to gastro-oesophageal reflux. Undigested pills in the refluxate had contacted oesophageal mucosa, leading to pill-induced oesophageal injury. This, along with vomiting, is postulated to have led to the oesophageal intramucosal dissection. She improved with conservative medical management with a clear liquid diet and proton pump inhibitors, and a follow-up upper endoscopy 1 week later showed recovery of the previously seen intramucosal dissection.

Gastroduodenal mucosal defense.

PURPOSE OF REVIEW: To review recent developments in the field of gastroduodenal mucosal defense. RECENT FINDINGS: Research in the field of gastroduodenal mucosal defense has focused on continued elucidation of molecular mechanisms that protect the mucosa and influence healing at the cellular level. Review of literature over the past year reveals that familiar proteins and mediators, such as nitric oxide, toll-like receptors, nucleotide-binding oligomerization domain-containing proteins (NOD2), ß-defensins, macrophages, dendritic cells, mucins, autophagy, and the influence of aging and diet, are still subjects of study, but also brings into light new processes and mediators, such as dual oxidases, defense against radiation injuries, and novel proteins such as ZBP-89. SUMMARY: These new published findings contribute to our overall understanding of gastroduodenal defense and suggest innovative avenues of future research and possible novel therapeutic targets.

A novel phosphorus repletion strategy in a patient with duodenal perforation.

We describe a case in which a patient receiving parenteral nutrition (PN) developed hypophosphatemia. Due to lack of availability of parenteral phosphate supplements, we chose to restore phosphate using diluted hypertonic sodium phosphate enemas. Due to the recent shortages of parenteral minerals and vitamins, such an alternate means of repletion is of increasing importance. Diluted hypertonic sodium phosphate enemas are inexpensive, easy to administer, and effective since phosphate is readily absorbed across the rectal mucosa. We hope that through this type of repletion, life-threatening hypophosphatemia among patients receiving PN can be avoided.

Gastroduodenal mucosal defense.

PURPOSE OF REVIEW: To review recent developments in the field of gastroduodenal mucosal defense. RECENT FINDINGS: Research in the field of gastroduodenal mucosal defense has focused on continued elucidation of molecular mechanisms that protect the mucosa and influence healing at the cellular level. Review of literature over the past year reveals focus on familiar processes such as superoxide dismutase, nitric oxide, heme oxygenase-1, neutrophil infiltration, cysteamine, mucin, hydrogen sulfide, ghrelin, adiponectin and the influence of Helicobacter pylori, but also brings into light new processes such as the balance between apoptosis and cellular proliferation, as well as the influence of other organ systems such as the bone marrow and central nervous system on the gastrointestinal tract. SUMMARY: These new published findings contribute to our overall understanding of gastroduodenal defense and suggest innovative avenues of future research and possible novel therapeutic targets.

Agrin regulation of alpha3 sodium-potassium ATPase activity modulates cardiac myocyte contraction.

Drugs that inhibit Na,K-ATPases, such as digoxin and ouabain, alter cardiac myocyte contractility. We recently demonstrated that agrin, a protein first identified at the vertebrate neuromuscular junction, binds to and regulates the activity of alpha3 subunit-containing isoforms of the Na,K-ATPase in the mammalian brain. Both agrin and the alpha3 Na,K-ATPase are expressed in heart, but their potential for interaction and effect on cardiac myocyte function was unknown. Here we show that agrin binds to the alpha3 subunit of the Na,K-ATPase in cardiac myocyte membranes, inducing tyrosine phosphorylation and inhibiting activity of the pump. Agrin also triggers a rapid increase in cytoplasmic Na(+) in cardiac myocytes, suggesting a role in cardiac myocyte function. Consistent with this hypothesis, spontaneous contraction frequencies of cultured cardiac myocytes prepared from mice in which agrin expression is blocked by mutation of the Agrn gene are significantly higher than in the wild type. The Agrn mutant phenotype is rescued by acute treatment with recombinant agrin. Furthermore, exposure of wild type myocytes to an agrin antagonist phenocopies the Agrn mutation. These data demonstrate that the basal frequency of myocyte contraction depends on endogenous agrin-alpha3 Na,K-ATPase interaction and suggest that agrin modulation of the alpha3 Na,K-ATPase is important in regulating heart function.