Levels of plasma cytokines and circulating endotoxin were assessed in 41 patients with severe intra-abdominal sepsis. Comparison was made with the Acute Physiology And Chronic Health Evaluation (APACHE) II scoring system. Blood samples were taken within 24 h of onset of the sepsis syndrome and at serial times thereafter. Increased levels of interleukin (IL) 6 (range 50-25,500 pg/ml) were detectable in all patients with sepsis. Eighteen of the 19 deaths were attributable to sepsis and higher levels of IL-6 at the onset of the sepsis syndrome correlated with a poor outcome. The sensitivity of IL-6 concentration in predicting mortality was 86.4 per cent with a specificity of 78.9 per cent and an overall correct classification rate of 82.9 per cent. IL-6 level was a better predictor than APACHE II score (sensitivity 72.7 per cent, specificity 57.9 per cent, correct classification rate 65.9 per cent). Levels of tumour necrosis factor alpha, IL-1 beta and endotoxin did not correlate with mortality rate. Plasma IL-6 concentrations may help in planning future strategies to decrease the mortality rate associated with sepsis.

No abstract

No abstract

We have undertaken a prospective randomized trial of one month's antimicrobial therapy for patients with symptomatic relapse of Crohn's disease. Criteria for entry included two major symptoms: fever, abdominal pain, diarrhea, weight loss, abdominal mass or complications (excluding perianal disease); and two hematologic abnormalities: hemoglobin, ESR, albumin, C reactive protein, iron, or total iron binding capacity. Patients were monitored for the aforementioned clinical and hematologic (hemoglobin, albumin, CRP) parameters over six weeks and for changes in fecal flora. Randomization was to four groups: metronidazole alone (M), cotrimoxazole alone (C), metronidazole and cotrimoxazole (C plus M), or double placebo (P). Seventy-two patients entered the study (18 = M, 16 = C, 21 = C plus M, 17 = P). After two weeks, improvement was reported as follows: M = 67 percent, C = 17 percent, C plus M = 71 percent, P = 35 percent. In the metronidazole group, two patients required surgery and one had troublesome side effects. In the cotrimoxazole group, two had side effects. In the combined group (C plus M), four had troublesome side effects and two of the placebo group (P) required operation. By four weeks, there was no difference in response among the groups: (M = 44 percent, C = 62 percent, C plus M = 57 percent, P = 41 percent). Antimicrobials had no effect on fecal flora or hematologic parameters. These results indicate that antimicrobials have little therapeutic potential for relapse of intestinal Crohn's disease.

Increased cytokine expression occurs in both active UC and pouchitis and to a lesser extent in the long-standing ileoanal pouch.

A study was performed to investigate whether acute reservoir ileitis (pouchitis) is associated with specific changes in mucosal morphology, crypt cell kinetics and faecal bacteriology in the ileal pouch. Forty-six patients were studied (ileal reservoir, 36; end ileostomy, ten) using clinical grading, sigmoidoscopy and biopsy; 24 patients with a reservoir were restudied after therapy for 1 month with metronidazole 400 mg three times daily. An index of villus atrophy and crypt cell production rate (CCPR) were determined in all biopsy material. Faecal bacteriology was assessed in 12 patients with a pouch before and after metronidazole therapy. The mucosa of patients with pouchitis was associated with a lower villus atrophy index (P = 0.052), a higher CCPR (P = 0.03) and a higher grade of acute inflammation than that in those without pouchitis. There was no difference in faecal bacterial counts between patients with and without pouchitis. A low atrophy index correlated with a high CCPR (P < 0.001), worse functional score (P < 0.001) and more severe pouch mucosal acute inflammation (P < 0.001), but not with faecal bacteriology. Following metronidazole therapy there was resolution of acute pouch inflammation, increased villus atrophy index (P = 0.049), decreased CCPR (P = 0.049) but no differences in faecal bacterial counts apart from Bacteroides species. These data show that metronidazole therapy does not specifically alter the growth of common faecal bacteria in patients with pouchitis, apart from Bacteroides species. However, metronidazole causes resolution of the typical changes in pouch mucosal morphology and crypt cell kinetics associated with pouchitis.

The high incidence of clinical remission after faecal diversion for Crohn's colitis suggests the faecal stream may play a part in the inflammatory mechanism. The effect of faecal diversion (n=22) and restoration of intestinal continuity (n=10) was assessed in patients with Crohn's colitis and compared with controls. Faecal diversion produced significant improvement in the disease activity index mean (SEM) (before 176 (9); after 114 (9), p

No abstract