Short chain fatty acid rectal irrigation for left-sided ulcerative colitis: a randomised, placebo controlled trial.

BACKGROUND: Short chain fatty acid (SCFA) deficiency is associated with colitis in animals and humans, and the mucosal metabolism of these compounds is decreased in ulcerative colitis. AIMS: To assess the efficacy of topical SCFA treatment in ulcerative colitis. PATIENTS AND METHODS: 103 patients with distal ulcerative colitis were entered into a six week, double-blind, placebo controlled trial of rectal SCFA twice daily; patients who were unchanged on placebo were offered SCFA in an open-label extension trial. RESULTS: Of the 91 patients completing the trial, more patients in the SCFA treated than in the placebo treated group improved (33% v 20%, p = 0.14, NS). Those on SCFA also had larger, but statistically non-significant, reductions in every component of their clinical and histological activity scores. In patients with a relatively short current episode of colitis (< 6 months, n = 42), more responded to SCFA than to placebo (48% v 18%, p = 0.03). These patients also had larger, but statistically non-significant, decreases in their clinical activity index (p = 0.08 v placebo). Every patient who improved used at least five of six of the prescribed rectal SCFA irrigations, whereas only 37% who did not improve were as compliant. In the open-label extension trial, 65% improved on SCFA; these patients also had significant reductions (p < 0.02) in their clinical and histological activity scores. CONCLUSIONS: Although SCFA enemas were not of therapeutic value in this controlled trial, the results suggest efficacy in subsets of patients with distal ulcerative colitis including those with short active episodes. Prolonged contact with rectal mucosa seems to be necessary for therapeutic benefit.

Rectal irrigation with short-chain fatty acids for distal ulcerative colitis. Preliminary report.

Colon cells from patients with ulcerative colitis utilize short-chain fatty acids inefficiently and may be exposed to decreased concentrations of these compounds. To test whether irrigation of the inflamed mucosa with short-chain fatty acids is useful, we conducted a six-week preliminary trial in 12 patients with distal colitis. Each patient used twice daily rectal irrigations with 100 ml of a solution containing acetate (80 mM), propionate (30 mM), and butyrate (40 mM). Two patients stopped at three weeks, one because of no improvement and the other because of complete resolution of symptoms. Of the 10 who completed the trial, nine were judged to be at least much improved and showed a change in a mean disease activity index score from 7.9 +/- 0.3 (SE) to 1.8 +/- 0.6 (SE) (P less than or equal to 0.002) and in a mucosal histology score from 7.7 +/- 0.7 (SE) to 2.6 +/- 0.7 (SE) (P less than or equal to 0.002). Thus, ulcerative colitis patients appear to benefit from increased contact with or higher than usual levels of these critical energy substrates.

Bilateral adrenal hemorrhage as a complication of intravenous ACTH infusion in two patients with inflammatory bowel disease.

We report two patients with inflammatory bowel disease in whom intravenous corticotropin therapy was complicated by bilateral adrenal hemorrhage. In one, the initial presentation was acute and unilateral, simulating colonic perforation and/or abscess. The diagnosis was made only at exploratory laparotomy. In the second patient, the presentation was subacute; multiple episodes of adrenal hemorrhage occurred subsequent to the course of corticotropin, and ultimately, hypoadrenalinism developed. Pertinent clinical and computed tomographic findings are reviewed.

Organic anions and the diarrhea of inflammatory bowel disease.

To determine if organic anions contribute to the diarrhea of inflammatory bowel disease, we measured osmolality, electrolytes, short-chain fatty acids, lactic acid, and some Krebs cycle anions in 24-hr fecal collections from 18 patients with chronic ulcerative colitis, 20 with Crohn's disease of the colon, and 16 normals. Mean lactic acid concentration was significantly elevated in ulcerative and Crohn's colitis, but values correlated with fecal weight only in the former syndrome. In ulcerative colitis, concentrations of each short-chain fatty acid, especially butyrate, were decreased compared with those from normals or Crohn's disease. Lactate and short-chain fatty acids accounted for nearly half the variability in fecal weight in ulcerative colitis. Crohn's patients had elevated mean fecal water osmolality and osmotic gap not observed in ulcerative colitis. Increased lactic acid and/or deficient short-chain fatty acids may modulate the diarrhea of ulcerative colitis. This mechanism seems less important in Crohn's colitis where an additional osmotic component may be significant.

Composition of fecal water. Comparison of "in vitro" dialysis with ultrafiltration.

We describe a simple method for the collection of stool water using dialysis membrane tubing placed directly into the feces. When the membrane was placed in pure aqueous solutions or in homogenized feces stored at 4 degrees C, equilibration for solutes was complete in 24 h. Exchangeable ions, short chain fatty acids, osmolality, and pH were measured in the fecal water of 8 normal subjects and 36 patients affected by different diarrheal diseases. The composition of fecal water collected by this method was almost identical to that obtained by ultrafiltration of feces immediately after collection. Differences, when present, were minimal (about 4%) and practically irrelevant. This in vitro dialysis method is simple, inexpensive, and seems particularly suitable for the measurement of osmolality, electrolytes, and short chain fatty acid concentrations in large numbers of fecal samples.

Azathioprine-associated pulmonary dysfunction.

We present a case of azathioprine-associated alveolitis diagnosed by gallium-67 scanning and transbronchial biopsy. The patient denied respiratory symptoms, exhibited spiking fevers, and had normal chest roentgenograms. Allopurinol inhibition of azathioprine metabolism may have been a contributing factor.

Control of upper gastrointestinal bleeding with a microcrystalline collagen hemostat.

A microcrystalline collagen hemostat (MCH) widely used in general surgery was tested in the control of bleeding from experimentally produced gastric ulcers. Five dogs had a gastrotomy and were given heparin. Using the standard "ulcer maker," three sets of three ulcers were made in the gastric mucosa of each animal. Blood from each ulcer was collected for a 5-min period to allow for stabilization of bleeding. MCH powder or slurry or no MCH was placed directly on one ulcer of each set in random order. The bleeding rate for the next 10 min was measured. Mean decrements in the bleeding rate for slurry MCH and dry MCH-treated ulcers were 87% and 81%, respectively, compared with 51% for controls, P less than 0.05. Twelve MCH-treated ulcers, but no control ulcer, stopped bleeding completely, P less than 0.01. Preliminary observations show that MCH slurry can be applied through an endoscope and may be hemostatically effective in man. MCH may have a role in the endoscopic control of gastrointestinal bleeding.

Comparison of the composition of faecal fluid in Crohn's disease and ulcerative colitis.

We determined the ionic composition of faecal fluid from 13 patients with Crohn's disease limited to the colon, 10 with diffuse ulcerative colitis, and eight with ulcerative proctitis. The Crohn's and colitis groups had similar proportions of colon surface involved radiographically and similar 24 hour faecal weights. However, Crohn's patients' faecal fluid had arithmetically lower mean sodium and statistically lower mean chloride (34.8 mmol/l +/- 16.2 SD vs. 53.1 mmol/l +/- 23.1 SD) and higher potassium (49.2 mmol/l +/- 20.2 SD vs. 33.0 mmol/l +/- 13.8 SD) concentrations (p less than 0.05 for each) and much higher osmolality (487.1 mOsmol/kg +/- 87.1 SD vs. 341.1 mOsmol/kg +/- 88.9 SD, p less than 0.001). Separation of these patients using the faecal osmotic gap agreed with the clinical classification in 86% of cases. The diarrhoea of proctitis patients had a nearly normal ionic composition which was clearly distinguishable from that of diffuse colitis. These results suggest differences in the composition and perhaps the pathogenesis of the diarrhoea of Crohn's and ulcerative colitis. The composition of fluid may prove a useful, non-invasive method for classifying patients with inflammatory bowel disease and, in ulcerative colitis, determining the extent of the inflammatory process.

Esophageal manifestations of Crohn's disease.

Two patients with concurrent esophagitis and ileocolitis due to Crohn's disease are presented. The initial feature of esophageal involvement was dysphagia caused by severe inflammation of the distal esophagus with mucosal ulcerations and polypoid folds. Long-term observation of both cases revealed a gradually progressive course leading to development of rigid esophageal structure, intramural sinus tract, and esophagobronchial or esophagogastric fistulas. The clinical and radiographic manifestations of Crohn's esophagitis in these 2 patients and in 18 previously reported cases are reviewed.

The colon influences ileal resection diarrhea.

Fecal mass and electrolyte concentrations from 25 ileectomy and/or colectomy patients on known diets were used to assess those factors most responsible for their diarrhea. In 18 ileectomy patients the severity of diarrhea, expressed as a fecal weight, was a function of both percent of colon and centimeters of ileum removed. Linear regression analysis, however, showed that the extent of missing colon had three times the effect of missing ileum on fecal weight. Patients who lost the ileocecal valve and part of the right colon had more diarrhea than those who lost comparable lengths of ileum but had this area preserved. Fecal ion concentrations seemed independent of diet but were related to fecal weight and the amount of colon and ileum removed. Potassium concentration was strongly dependent on the amount of colon lost, while sodium concentration was more influenced by the length of resected ileum. Choloride was most dependent on fecal weight. As expected, fecal fat correlated strongly with the extent of ileum removed. Regresison equations were constructed from the electrolyte data which described and predicted the extent of lost ileum or colon. Our data were also used to separate patients with less than 100 cm of ileum removed from those with more extensive resections. The severity of diarrhea following ileal resection depends primarily on the amount of contiguous colon removed. Varying loss of ileum and colon produced predictable effects on fecal weight and electrolyte composition. Surgeons should preserve the maximum amount of colon possible to reduce the severity of diarrhea in these patients.

Pancreatic duct arteriovenous fistula and the metastatic fat necrosis syndrome.

This report summarizes the course of a patient with asymptomatic chronic pancreatitis associated with hemorrhage into the pancreatic duct and metastatic fat necrosis. Retrograde cannulation of the pancreatic duct and superior mesenteric arteriography established the presence of a pseudocyst with a pancreatic duct-arteriovenous (DAV) fistula as the cause of the syndrome. Ligation of feeder vessels with external drainage of the cyst as the initial surgical procedure stopped the bleeding but failed to prevent recurrence of the pancreatic duct-venous fistula. A pancreaticoduodenectomy with resection of the cyst and fistula was required to arrest destruction of distant tissues. Although serum and urine amylase concentrations were markedly elevated, serum lipase levels were normal throughout the patient's course. Elevation of serum lipase does not seem to be a necessary condition for the development of the metastatic fat necrosis syndrome.

Gastric operations and glucose homeostasis. II. glucagon and secretin.

Alimentary hyperglycemia in patients who have undergone gastric operations may be due, in part, to altered intestinal signals for glucose disposition. We measured glucose, immunoreactive insulin (IRI) pancreatic glucagon (IRG), and glucagon-like immunoreactivity (GLI) after oral glucose in patients with prior antrectomy or vagotomy and pyloroplasty and in normal individuals. All subjects had normal assimilation coefficients for intravenous glucose, which suggests that the responsiveness of the pancreatic beta-cells had not been altered by the surgical procedures. The early hyperglycemic response to oral glucose and the associated elevation of plasma GLI were much greater and the IRI levels slightly higher in both experimental groups in comparison to normal subjects. A decrease in the level of IRG, albeit not statistically significant, was noted in all groups after the ingestion of glucose. In gastrectomy patients, secretin infusion during repeated oral glucose tolerance tests partially corrected the hyperglycemia and lowered plasma GLI and IRI levels. The responses of the vagotomy and pyloroplasty patients and of the normal subjects were not altered by secretin infusion. We conclude that the intolerance or oral glucose after gastric surgery may be related to elevated GLI levels, and that the beneficial effect of secretin may be due to its ability to decrease these levels.

Urinary crystalloid excretion in patients with inflammatory bowel disease.

Because of the potential relationship of increased urinary crystalloid excretion and concentration to stone formation, urinary calcium and uric acid excretion patterns were studied prospectively in 65 patients with inflammatory bowel disease and compared with excretion patterns in patients with functional bowel disease (controls) receiving similar dietary prescriptions. Mean 24-hr urinary calcium excretion was higher in both ulcerative colitis (212 mg, p <0.02) and granulomatous bowel disease (168 mg, p = n.s.) than in controls (118 mg). Urinary calcium excretion exceeded 250 mg/24 hr in 11 of 34 patients with inflammatory bowel disease but in none of the controls. Eight of these 34 patients compared with one of 10 controls excreted urine with calcium concentrations greater than 20 mg/100 ml. Mean 24-hr uric acid excretion was slightly higher in granulomatous bowel disease (520 mg) than in ulcerative colitis (450 mg) or functional bowel disease (451 mg). Eight patients with inflammatory bowel disease but no control subject excreted > 700 mg. The mean urinary uric acid concentration was significantly higher in ulcerative colitis (538 mug/ml, p <0.05) and granulomatous bowel disease (558 mug/ml, p <0.02) than in controls (338 mug/ml). The mean morning urine pH was lower (5.5, p <0.01) in ulcerative colitis than in the other groups.These results indicate increased excretion and higher concentration of calcium and uric acid in some patients with inflammatory bowel disease on the usual treatment programmes. Only very long-term prospective studies of such patients can help to document the true contribution of increased crystalloid concentration and excretion to kidney stone formation in inflammatory bowel disease patients.