Samuel Meyers

Olsalazine sodium in the treatment of ulcerative colitis among patients intolerant of sulfasalazine: A prospective, randomized placebo-controlled, double-blind, dose-ranging clinical trial

Sixty-six outpatients with active ulcerative colitis who were intolerant of sulfasalazine were treated in a double-blind randomized trial. They received placebo or olsalazine sodium in daily doses of 0.75, 1.5, or 3 g. Overall, 35% of patients receiving olsalazine improved clinically, compared to 16% of patients receiving placebo. When the colitis activity at study entry was compared with that observed at the completion of the study period, statistically significant or nearly significant improvement was demonstrated within the combined olsalazine group (p = 0.01) and within patient groups receiving olsalazine at daily doses of 1.5 g (p = 0.04) and 3 g (p = 0.055). A dose-response relationship was suggested because 16%, 29%, 27%, and 50% of patients improved in the placebo and 0.75-, 1.5-, and 3-g olsalazine groups, respectively, (p = 0.04). A similar pattern of improvement was seen when sigmoidoscopic criteria were used, although a dose-response relationship was not demonstrated. There were no differences between the treatment and placebo groups for any of the adverse effects or laboratory variables reported at baseline or during the trial period. Four patients were withdrawn because of adverse reactions: 2 developed a skin rash while receiving olsalazine and 2 had diarrhea, one while on olsalazine and the other while on placebo. The data suggest that olsalazine is effective for the treatment of ulcerative colitis and is well tolerated among patients intolerant to sulfasalazine.

Predicting the Outcome of Corticoid Therapy for Acute Ulcerative Colitis: Results of a Prospective, Randomized, Double-blind Clinical Trial

We looked for factors predicting the therapeutic outcome in 66 patients with severe ulcerative colitis treated with intravenous hydrocortisone or corticotropin (ACTH) for 10 days. Patients were randomized before therapy within strata defined by whether they had received oral corticosteroids continuously before the study (group A, 35 patients) or not (group B, 31 patients). Comparisons were made between groups receiving what we considered optimal corticoid therapy, hydrocortisone for group A and ACTH for group B. Overall, therapeutic success was achieved in 28 (42%), with a median time of 7.5 days. Favorable factors measured on admission to the study were those suggesting less severe colitis activity: absence of fulminant disease, limited disease extent, a shorter duration of the present attack, fewer stools, a lower erythrocyte sedimentation rate (ESR), and a higher hemoglobin. Factors compatible with more severe colitis including fulminant activity, more extensive disease, a shorter total disease duration, bloody stools, and fewer bowel movements, favored an early response among those patients who were to achieve a remission. Prolonging therapy beyond 10 days by switching to the alternate corticoid drug did not improve the remission rate. Achieving remission during the initial therapy period, especially when it occurred early, was the most important predictive factor for a favorable clinical course during the following year. Prolonging therapy did not improve the 1-year remission rate. In fact, a higher proportion of patients who continued to require therapy underwent colectomy than those who received one treatment course.

Colchicine therapy of the renal amyloidosis of ulcerative colitis.

Two patients with severe proteinuria, due to renal amyloidosis complicating chronic ulcerative colitis, improved remarkably with colchicine therapy. One patient with an initial daily urine protein excretion of 13.70 g had a reduction within 2 mo to 6.50 g and to 0.37 g after 9 yr. The other patients daily urine protein excretion was 9.00 g. This was reduced to 5.10 g/day within 3 mo and was 0.53 g/day by 8 mo. Renal function remained stable or improved during the period of therapy. Colchicine resulted in rapid and prolonged benefit for these patients, despite their amyloid-induced nephrotic syndrome.

Periileostomy fistulae in Crohn's disease.

Fifteen of 214 patients with an ileostomy constructed during the course of Crohns disease developed periileostomy fistulae. In each case this was the consequence of recurrent ileal disease. The incidence was higher in female patients as well as those with a prior history of either intraabdominal abscess or any type of fistula. Periileostomy fistulae are frequently multiple. In addition to the clinical features of recurrent disease, periileostomy fistulae cause additional symptoms that are particularly distressing. These result from the proximity of the fistula to the stoma and the difficulty of maintaining the seal of an appliance. All periileostomy fistulae require resection and reconstruction of the stoma. Superficial fistulae with relatively smooth skin around the stoma may be reconstructed using the original stoma site; but deep fistulae with severe peristomal excoriation, induration and inflammation require transposition to a different quadrant. This may, in suitable cases, be carried out by direct stoma-to-stoma transposition, without formal lap-arotomy. The quality of life following successful reconstruction of the stoma is excellent, even though some patients will develop additional recurrent disease. To date none of these patients have developed another periileostomy fistula.

Does Intestinal Resection Heal the Pyoderma Gangrenosum of Inflammatory Bowel Disease

A retrospective study of nine patients with active pyoderma gangrenosum at the time of operation for inflammatory bowel disease showed two patterns of postoperative skin healing: 1) prompt healing within 2 months, occurred in five patients with moderate to severe inflammatory bowel disease. 2) skin disease persisted in four others, healing only after a year. Three of these patients had mild ulcerative colitis, and in them, the operation was carried out in the hope of curing crippling pyoderma gangrenosum. The fourth patient had only an intestinal bypass for ileitis. Our observations suggest that prompt skin healing may occur after surgery in patients with severe inflammatory bowel disease, but not necessarily in those with milder bowel disease or in those in whom some bowel disease persists.

Reduction of Gastric Ammonia by Ampicillin in Normal and Azotemic Subjects

Ampicillin was tested with regards to its capacity to reduce gastric ammonia production in basal and betazole-stimulated gastric secretion. A 7-day course of oral ampicillin (4 g per day) reduced basal gastric ammonia concentration from 5.5 +/- 1.4 to 1.8 +/- 0.3 mM and postbetazole ammonia from 4.7 +/- 0.9 to 1.3 +/- 0.3 mM (P less than 0.01) in 7 control subjects. Similar results were obtained after oral neomycin (4 g per day) or intramuscular ampicillin (4 g per day), each given to a separate group of 7 control subjects. In 5 azotemic patients, oral ampicillin treatment resulted in a reduction of ammonia concentration from 16.3 +/- 4.7 to 3.1 +/- 0.7 mM in basal secretion and from 18.3 +/- 8.1 to 2.3 +/- 0.6 mM in betazole-stimulated gastric juice (P less than 0.01). Antibiotic therapy did not alter volume of gastric secretion. Gastric acidity appeared lower in azotemic patients and increased significantly after treatment, indicating that the higher ammonia content could account for at least part of the hypoacidity. Because ampicillin is active orally as well as parenterally and can be readily used in renal failure, it may be of value for the treatment of hepatic encephalopathy, especially in the azotemic patient in whom neomycin is toxic.

T AND B LYMPHOCYTES AND CUTANEOUS ANERGY IN INFLAMMATORY BOWEL DISEASE

The cellular immune status of patients with inflammatory bowel disease (IBD) has been a focus of attention and controversy for over 35 yr. Some studies of in vitro and in vivo indicators of cellular immunity have shown impairments in the immune mechanisms of patients with Crohn’s disease (CD),’-7 whereas other investigators have considered these mechanisms to be normaL8-” Meanwhile, most published reports seem to agree that cellular immunity is not defective in patients with ulcerative colitis (UC).4*677,’o*12-’4 Our own previous studies, on the other hand, led us to the conclusion that there was indeed a defect in cellular immunity in a substantial proportion of patients with IBD, both CD and UC alike. This conclusion was based principally upon our finding of impaired peak lymphocyte responsiveness to graded doses of the nonspecific plant mitogen phytohemagglutinin (PHA) among approximately one-third of our IBD patients with either CD or UC.” In the present study we have strengthened our previous conclusion by demonstrating depressions in circulating T-lymphocyte populations among 32 1BD patients with either CD or UC. We have also found elevations in B lymphocytes among 77 IBD patients of both categories as well as a high incidence of anergy upon skin testing with 2,4-dinitrochlorobenzene (DNCB) among 29 IBD patients of both types.

Pancreatitis coincident with Crohn's ileocolitis: report of a case and review of the literature

A young woman who developed acute pancreatitis coincident with Crohns disease is presented. The pancreatitis was documented by pancreatic hyperamylasemia, elevated urine amylase activity, abdominal sonogram, computed tomography, and laparotomy. A cause-and-effect relationship has not been established, however; no etiology other than the Crohns disease, which was confined to the ileum and colon, could be identified. Surgical removal of the severely involved ileum led to the resolutionof the pancreatitis. A possible relationship between acute pancreatitis and Crohns disease is proposed, although potential pathophysiologic mechanisms are unknown. The diagnosis of pancreatic involvement in such cases may make an important contribution to therapy.