Postheparin plasma diamine oxidase in health and intestinal disease.
In animals, the distribution of the enzyme diamine oxidase is confined, almost exclusively, to the small bowel mucosa. In humans, plasma diamine oxidase is at or below assay detection limits but can be liberated into the circulation from binding sites in the intestine by i.v. heparin. Therefore, the authors wished to see if diamine oxidase could be released by a low and safe dose of heparin (5000 U) and if the resultant area under the concentration-time curve would provide a noninvasive marker of segmental intestinal disease. In 17 control subjects, the mean area under the curve (following administration of 5000 U i.v. heparin) was 35.9 +/- 5.0 (SEM) mU.L-1.2 h-1; in 6 individuals studied on two separate occasions, postheparin plasma diamine oxidase profiles were reproducible (r = 0.98; p less than 0.001). The longitudinal distribution of diamine oxidase in the gastrointestinal tract, measured in 12 gastric, 16 jejunal, 6 ileal, and 18 colonic biopsies, was similar in humans to that found in animals. In patients with normal peroral biopsies, there was a linear relationship between jejunal mucosal and postheparin plasma diamine oxidase activities (r = 0.84; p less than 0.01). The areas under the curve in controls were then compared with those in patients with segmental intestinal diseases: 21 with ileal disease with or without colonic Crohn's disease (10 unoperated and 11 with ileal resection), 7 with non-Crohn's ileal resection, 8 with ulcerative colitis, 10 with untreated and 7 with treated celiac disease (6 studied before and after a gluten-free diet), and 5 studied during total parenteral nutrition and again after resumption of oral feeding. The results in the 18 ileectomized patients were subdivided into those with major (arbitrarily greater than 75 cm) and minor (less than 75 cm) resections. Areas under the curve were markedly reduced in nonresected Crohn's patients (6.0 +/- 1.79 mU.L-1.2 h-1; p less than 0.001 vs. controls), correlating inversely, in a first-order relationship, with disease activity (r = 0.82; p less than 0.001) and returning toward normal in 4 patients achieving disease remission. Low areas under the curve in total parenteral nutrition patients (4.5 +/- 0.9; p less than 0.001) were also reversible on resumption of oral feeding. However, areas under the curve were not significantly lower in patients with limited ileal resection (less than or equal to 75 cm), with celiac disease (untreated and treated), or ulcerative colitis than in controls.(ABSTRACT TRUNCATED AT 400 WORDS)
Rokkas
T
T
Gastroenterology Unit, United Medical School of Guy's Hospital, London.
Vaja
S
S
Murphy
G M
GM
Dowling
R H
RH
D000293:Adolescent; D000328:Adult; D006631:Amine Oxidase (Copper-Containing) / Q000097:blood*; D002446:Celiac Disease / Q000201:enzymology; D003093:Colitis, Ulcerative / Q000201:enzymology; D003106:Colon / Q000201:enzymology; D003424:Crohn Disease / Q000201:enzymology; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007077:Ileal Diseases / Q000201:enzymology; D007082:Ileum / Q000201:enzymology; D007275:Injections, Intravenous; D007410:Intestinal Diseases / Q000201:enzymology*; D007413:Intestinal Mucosa / Q000201:enzymology*; D007583:Jejunum / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D010289:Parenteral Nutrition, Total; D015203:Reproducibility of Results
D006493:Heparin; D006631:Amine Oxidase (Copper-Containing)