Denise Youngs

Cytokine production in pouchitis is similar to that in ulcerative colitis

PURPOSE: Controversy exists as to whether pouchitis represents a reactivation of the immunologic mechanisms that lead to ulcerative colitis (UC). The aims of this study were to determine local levels of the cytokines: interleukin-1β(IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNFα) in the mucosa of patients with “asymptomatic” ileoanal pouch (n=25), pouchitis (n=9), active UC (n=20), normal ileum (n=15), proctitis (n=10), and normal colon (n=15). METHODS: Lamina propria mononuclear cells were isolated from mucosal biopsies by enzymatic dispersion and cultured for 48 hours. Proinflammatory cytokine levels were measured in the supernatants by enzyme-linked immunosorbent assay. RESULTS: IL-1β,IL-6, IL-8, and TNFαsecretions were significantly greater in pouchitis and active UC than in the noninflamed ileoanal pouch and normal controls (P<0.001). There was significant correlation (r=0.63,P< 0.05) between levels of cytokines expressed in pouchitis and active UC. CONCLUSIONS: Increased cytokine expression occurs in both active UC and pouchitis and to a lesser extent in the long-standing ileoanal pouch.

Antibiotic therapy for treatment in relapse of intestinal Crohn's disease

We have undertaken a prospective randomized trial of one months antimicrobial therapy for patients with symptomatic relapse of Crohns 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 trouble-some 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 Crohns disease.

Oral neomycin and erythromycin compared with single-dose systemic metronidazole and ceftriaxone prophylaxis in elective colorectal surgery

A prospective randomized trial was performed to compare oral neomycin and erythromycin with single-dose intravenous metronidazole and ceftriaxone in elective colorectal surgery. The study was discontinued after 60 patients were entered. The overall rate of infection was 41 percent in the oral neomycin and erythromycin group (n = 29) compared with 9.6 percent in those who received intravenous metronidazole and ceftriaxone (n = 31) (p less than 0.01). Infections in the oral group were principally due to resistant Staphylococcus aureus, Bacteroides fragilis, and Escherichia coli. Preoperative administration of oral neomycin and erythromycin was associated with a significant reduction of Escherichia coli counts (1 X 10(7) to 3 X 10(5) organisms/ml, p less than 0.05) compared with the intravenous group, but there was no significant reduction in the counts of Bacteroides fragilis (2 X 10(8) to 1 X 10(7) organisms/ml) and there was an increase in the counts of Clostridia (2 X 10(4) to 1 X 10(6) organisms/ml). These results indicate that single-dose systemic prophylaxis with appropriate antibiotics is superior to oral neomycin and erythromycin.

Faecal diversion for Crohn's colitis: a model to study the role of the faecal stream in the inflammatory process.

The high incidence of clinical remission after faecal diversion for Crohns 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 Crohns colitis and compared with controls. Faecal diversion produced significant improvement in the disease activity index mean (SEM) (before 176 (9); after 114 (9), p < 0.01) and serum albumin concentrations (before 33 (3.0); after 38 (3.0), p < 0.05) in all patients with Crohns colitis. The crypt cell production rate (CCPR) was maintained after faecal diversion for Crohns colitis but fell in the control group (before = 3.6 (0.8)), at two (1.4 (0.4), p < 0.02), and six weeks (1.6 (0.4), p < 0.05). Mucosal glucosamine synthetase activity, reflecting glycoprotein synthesis, was significantly lower in patients with Crohns colitis (analysis of variance p < 0.05) after diversion but was maintained in the control group. Restoration of intestinal continuity failed to produce reciprocal changes. The sustained cellular proliferation and fall in glycoprotein synthesis in Crohns colitis after faecal diversion may represent the end of an exaggerated protective response and regenerative hyperplasia after exclusion of the faecal stream. This study suggests the faecal stream may participate in the inflammatory process in Crohns colitis. The underlying mechanism is unknown.

Clostridium difficile toxin in acute diarrhoea complicating inflammatory bowel disease.

The incidence of Clostridium difficile cytotoxin has been studied in 69 consecutive patients with inflammatory bowel disease complicated by severe diarrhoea or ileostomy flux during 74 admissions to hospital. The cytotoxin was identified in only four patients, all of whom had received antimicrobials. Clostridium difficle, but not cytotoxin, was identified in 10 of 43 admissions. This followed antimicrobial prophylaxis to cover a recent operation in two patients, and five were on long-term sulphasalazine. Only three patients with Clostridium difficile had not received an antimicrobial within one month of the study. Isolation of Clostridium difficile alone is of doubtful pathological significance, as it spontaneously disappeared without treatment in all patients.

Intragastric N-nitrosation is unlikely to be responsible for gastric carcinoma developing after operations for duodenal ulcer.

Three groups of patients studied after operations which had cured their duodenal ulcer were compared with a control group (no operation, n = 8). The surgical procedures included: proximal gastric vagotomy (n = 7), truncal vagotomy and pyloroplasty (n = 7), truncal vagotomy and antrectomy (n = 8). Samples of gastric juice were aspirated half hourly or hourly over 24 hours for measurement of pH, counts of all identified bacteria, nitrite and total N-nitrosocompounds. Although the pH over 24 hours was significantly higher after proximal gastric vagotomy (p less than 0.05) and truncal vagotomy and antrectomy (p less than 0.001) than controls, there was no difference between truncal vagotomy and pyloroplasty and controls. Counts of nitrate reducing bacteria over 24 hours were also significantly higher after truncal vagotomy and antrectomy than controls (p less than 0.1) but no differences were observed between the other groups. Only after truncal vagotomy and antrectomy was nitrite over 24 hours significantly increased compared with controls (p less than 0.01). Despite these higher values after truncal vagotomy and antrectomy, there was no significant difference in total N-nitrosocompounds between any of the four groups. Whereas bacterial counts and nitrite increased with pH, no correlation was found between total N-nitrosocompounds and pH. These results provide no evidence that exposure to total N-nitrosocompounds is increased after operations for duodenal ulcer.

The effect of peritoneal lavage with tetracycline solution on postoperative infection

A prospective randomized trial was performed to determine the value of tetracycline lavage in addition to systemic antibiotic prophylaxis in 159 patients undergoing elective and emergency intestinal operations. Tetracycline lavage was associated with a significant overall reduction in postoperative infection rates in 25 of 74 patients (34 percent) receiving saline lavage compared with 15 of 85 patients (18 percent) having tetracycline lavage (P<0.05). Tetracycline lavage was associated with a significant reduction in the counts of aerobic and anaerobic bacteria in the peritoneal fluid at the end of the operation (P<0.05 andP<0.01, respectively) and with a significant reduction of aerobes 24 hours postoperatively (P<0.02). Tetracycline lavage would appear to confer clinical benefit in preventing postoperative infection.

A Randomised Prospective Controlled Study of Ciprofloxacin with Metronidazole versus Amoxicillin/Clavulanic Acid with Metronidazole in the Treatment of Intra-Abdominal Infection

SummaryA prospective randomised study was undertaken in 80 patients to assess the combined regimen of ciprofloxacin with metronidazole against amoxicillin/clavulanic acid with metronidazole as treatment for established intra-abdominal infection. Treatment was for five days. Seventy-eight patients were clinically evaluable (38 patients on ciprofloxacin with metronidazole and 40 patients on amoxicillin/clavulanic acid with metronidazole). The overall clinical success rate in the treatment of intra-abdominal infections was 96% for the ciprofloxacin with metronidazole group, and 90% for the amoxicillin/clavulanic acid with metronidazole group. Over half of all patients were able to change from intravenous to oral antibiotic administration within the study period. One patient receiving ciprofloxacin with metronidazole developed pruritus near the injection site.Zusammenfassung80 Patienten mit gesicherter abdomineller Infektion wurden im Rahmen einer prospektiven randomisierten Studie entweder mit der Kombination Ciprofloxacin plus Metronidazol oder mit Amoxicillin/Clavulansäure plus Metronidazol behandelt; die Behandlungsdauer betrug fünf Tage. Zur klinischen Auswertung standen 78 Patienten zur Verfügung (38 Patienten waren mit Ciprofloxacin plus Metronidazol, 40 mit Amoxicillin/Clavulansäure plus Metronidazol behandelt worden). In der Ciprofloxacin-Metronidazol-Gruppe sprachen 96% der Patienten klinisch auf die Therapie an, in der Gruppe, die Amoxicillin/Clavulansäure plus Metronidazol erhalten hatte, 90%. Bei mehr als der Hälfte der Patienten konnte die Antibiotikatherapie nach anfänglicher intravenöser Gabe auf die orale Applikation umgestellt werden. Bei einem Patienten trat nach Gabe von Ciprofloxacin plus Metronidazol neben der Injektionsstelle Pruritus auf.

CANDIDACIDAL ACTIVITY OF CROHN'S DISEASE NEUTROPHILS

The ability of normal and Crohns disease neutrophils to kill Candida albicans has been studied using neutrophils isolated from peripheral blood and suspended in phosphate buffered saline at 5 x 10(6) cells per ml. C albicans was grown to a stationary phase in broth culture and suspended in phosphate buffered saline at 10(7) organisms/ml. Neutrophils and Candida were then incubated together at 37 degrees C in a shaking water bath in the presence of fresh serum. At 30 and 60 minutes samples were withdrawn, neutrophils lysed, and Candida survival assessed by colony counting. Results were compared with control suspensions of Candida incubated with serum alone. After 30 and 60 minutes in the presence of autologous serum normal neutrophils had killed significantly more Candida than Crohns disease neutrophils (mean (SD) 61.0 (16.7)% v 40.5 (16.2)% at 30 minutes, p less than 0.0001; 83.2 (7)% v 70.8) 16)% at 60 minutes, p less than 0.005). The results did not alter significantly when normal neutrophils were incubated with Candida in the presence of Crohns disease serum instead of normal serum. When Crohns disease neutrophils were incubated with Candida in the presence of normal serum instead of autologous serum there was some improvement in candidacidal ability at 30 minutes (48.9 (20.6)% v 40.5 (16.2)%, p less than 0.03) but not at 60 minutes. Phagocytosis, measured using a radiometric assay, was normal. Neutrophils from patients with Crohns disease have an impaired ability to kill this granuloma provoking organism. It is not due to serum inhibitors or defective phagocytosis.

Failure of antimicrobial prophylaxis with cefoxitin, or metronidazole and gentamicin in colorectal surgery. Is mannitol to blame?

Abstract In a prospective randomized trial of 72 patients undergoing elective colorectal surgery for malignant disease the incidence of post-operative infection after cefoxitin prophylaxis was 27 per cent compared with 31 per cent after metronidazole and gentamicin prophylaxis. Sepsis from Bacteroides species occurred in five patients after cefoxitin (one septicaemia) compared with only one after metronidazole and gentamicin. Sepsis with aerobic bacteria was more common in patients who had received pre-operative oral mannitol for bowel preparation. Oral mannitol bowel preparation was associated with higher counts of Escherichia coli in the colon than other methods of bowel preparation. Five cases of antibiotic associated colitis occurred, all in patients receiving cefoxitin.