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PURPOSE: The cytokines interleukin 1beta and interleukin 8 have previously been shown to be present in mucosal biopsy specimens from inflamed ileoanal pouches. Our aim was to use the method of whole gut lavage fluid to measure cytokine concentrations and relate these to disease activity. METHODS: Forty-two patients with ulcerative colitis were recruited (23 males). Their ages ranged from 20 to 73 years (median 39). A questionnaire was completed and whole gut lavage, pouchoscopy, and biopsy were performed. RESULTS: Both interleukin 1beta and interleukin 8 were present in the whole gut lavage fluid of ileoanal pouches, with concentrations ranging from 4 to 143 pg/ml (median 6.3 pg/ml) for whole gut lavage fluid interleukin 1beta and from 18 to 1000 pg/ml (median 53.7 pg/ml) for whole gut lavage fluid interleukin 8. Whole gut lavage fluid interleukin 1beta and interleukin 8 were simultaneously detectable in 24 patients. These included the five patients with pouchitis, who had higher levels of interleukin 1beta (75 pg/ml vs. 8 pg/ml, P < 0.005) and interleukin 8 (668 pg/ml vs. 106 pg/ml, P < 0.005) compared with the rest of the patients with detectable cytokines (n = 19). The sensitivity of whole gut lavage fluid interleukin 8 (>200 pg/ml) in the diagnosis of pouchitis was 1, and the specificity was 0.86. There was a significant positive correlation of both whole gut lavage fluid interleukin 1beta and interleukin 8 with all the gut protein loss markers (immunoglobulin G, albumin, alpha1-antitrypsin). CONCLUSION: Cytokine interleukin 1beta and interleukin 8 concentrations, along with other parameters of inflammation, are raised in pouchitis in the whole gut lavage. The results also suggest a spectrum of severity of "pouchitis," with clinical pouchitis fulfilling Moskowitz criteria at the severe end of the spectrum.

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OBJECTIVE: To prospectively compare two indices for diagnosis of pouchitis: Moskowitz criteria and pouchitis disease activity index (PDAI). PATIENTS AND METHODS: Fifty-six consecutive patients with an ileoanal pouch for ulcerative colitis were recruited. A clinical questionnaire was composed and the Oresland functional score calculated. Pouchoscopy and biopsy were performed after cleansing of the pouch. RESULTS: Seven patients had pouchitis according to both Moskowitz and PDAI ('positive' group). Five patients had PDAI > or = 7, but did not fulfil the Moskowitz criteria ('negative' group). The pouchoscopy and Oresland functional scores were similar between the two groups. The biopsy neutrophilia and ulceration were more prominent in the 'positive' group (chi2=5.18, P < 0.05), whereas urgency (chi2=8.4, P < 0.001), evacuation difficulties (chi2=5.18, P < 0.05) and history of bleeding per pouch (chi2=4.18, P < 0.05) were more pronounced in the 'negative' group. CONCLUSION: Moskowitz criteria may be broadly in agreement with the PDAI; these, however, cannot be regarded as interchangeable.

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OBJECTIVE: White cell scintigraphy has shown that neutrophils migrate into the gut wall and lumen in ileoanal pouches. We aimed to establish whether whole gut lavage fluid can be used to investigate intestinal neutrophil migration in ileoanal pouches. DESIGN: A prospective single centre study recruiting consecutive patients. METHODS: Whole gut lavage with polyethylene glycol electrolyte solution was performed in 56 (32 men, 24 women) ileoanal pouch patients who had undergone colectomy for ulcerative colitis; the first clear effluent was collected, processed and stored at -70 degrees C. The fluid was assayed for neutrophil granulocyte elastase using a specific colorimetric assay, IgG, albumin, alpha1-antitrypsin, haemoglobin and cytokines IL-1beta and IL-8 using previously described techniques. Patients' disease activity was characterized following pouchoscopy and biopsy. RESULTS: Patients with pouchitis had significantly higher levels of granulocyte elastase in whole gut lavage fluid compared with those without pouchitis. Patients with detectable granulocyte elastase had higher pouchoscopy score, more severe mucosal neutrophil infiltration and protein loss and bleeding. These patients had significantly higher levels of cytokines IL-1beta and IL-8 in the whole gut lavage fluid, compared with patients with undetectable granulocyte elastase. CONCLUSION: Whole gut lavage fluid samples may provide a useful investigative tool to study mucosal inflammation and luminal neutrophil migration in ileoanal pouches.

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BACKGROUND: Gut protein loss is a characteristic of inflammatory bowel disease (IBD), and immunoglobulin (Ig) G, albumin and alpha1-antitrypsin concentrations in whole gut lavage fluid (WGLF) correlate with clinical disease activity. If inflammation in ileoanal pouches is similar to IBD, then measurement of protein-losing enteropathy by analysis of WGLF may provide an objective assessment of disease activity in pouches. METHODS: Forty-two patients who had restorative proctocolectomy for ulcerative colitis underwent whole gut lavage with a polyethylene glycol-electrolyte solution. The first clear effluent was filtered, processed by the addition of protease inhibitors and stored at - 70 degrees C. IgG, albumin and alpha1-antitrypsin were assayed in WGLF. The Pouchitis Disease Activity Index (PDAI) was calculated after pouchoscopy and biopsy; the Moskowitz criteria for pouchitis were also applied. RESULTS: There was a significant correlation of the pouchoscopy score and the PDAI with the concentration of WGLF IgG. All patients with 'pouchitis' according to the Moskowitz criteria had a WGLF IgG concentration greater than 10 microg/ml. The WGLF albumin level also showed a significant correlation with the PDAI, but alpha1-antitrypsin concentration did not. CONCLUSION: Analysis of WGLF for IgG and albumin may be useful in the assessment of disease activity in pouch inflammation.

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The results of a policy of selective cholangiography were assessed in 400 patients undergoing laparoscopic cholecystectomy. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) was performed in 81 patients (20 per cent) of whom 31 (38 per cent) showed definite or possible evidence of stones in the bile duct. Seventeen of the 400 patients underwent intraoperative cholangiography and the majority of these (12) were normal. After a minimum follow-up of 1 year, 17 patients (4 per cent) have had ERCP for suspected residual duct stones. Eight (2 per cent) of these revealed stones and all were successfully treated with sphincterotomy and duct clearance. Preoperative and postoperative ERCP was not associated with mortality or major morbidity. No major duct injury occurred and none was diagnosed within 2 years of operation. Routine intraoperative cholangiography is not a necessary part of laparoscopic cholecystectomy in the presence of an efficient and safe ERCP service.

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The production of echinocandin B (ECB), a lipopolypeptide used for chemical manufacture of the anti-Candida agent Cilofungin, was accomplished by fermentation using a strain of Aspergillus nidulans. In addition to ECB, this fermentation also produces a significant amount of sterigmatocystin (ST), a potent carcinogen structurally related to the aflatoxins. Mutants blocked in the ST biosynthetic pathway were created by genetic modification of the polyploid production strain C747. The following steps were involved: (i) reduction of the genotype to haploid by treatment with the spindle fiber poison methyl 1-(butylcarbamoyl)-2-benzimidazole carbamate (MBC), using colony morphology, conidia size, and the ability to obtain 5-fluoro-orotic acid (5-FOA)-resistant mutants as criteria for ploidy; (ii) mutagenesis of a haploid isolate using UV irradiation; and (iii) screening of mutants for inability to produce ST by thin layer chromatography. Six mutants blocked in ST production were isolated. All six remained capable of producing ECB equivalent in quantity to the haploid strain C747-GR14. One of the mutants was shown to be the result of a chromosomal translocation.

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A geographically based cohort of 68 children with Crohn's disease was derived by sampling from Scottish Hospital In-patient Statistics. Surgical histories were examined and analysed by actuarial methods, and the nature of major operations performed was compared with operations for Crohn's disease in the Lothians' Surgical Audit. Fifty-four of the 68 patients were treated surgically, with a total of 135 operations (71 major, 64 minor). Fifty per cent of the cohort had a major operation within 5 years of onset of symptoms; median time to a second operation was 4 years. The types of major operation performed in juvenile onset patients differed significantly from those recorded in the Lothians' audit, with a high rate of exploratory laparotomy in younger patients (12 cases). With a mean follow-up of 7 years, 12 patients (18 per cent) have a permanent stoma. There were five deaths, three postoperative. This study highlights the frequency of surgical intervention in young people with Crohn's disease.

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A geographically based cohort of 37 children with ulcerative colitis has been derived by sampling from Scottish Hospital In-patient Statistics. Surgical histories were examined and analysed by actuarial methods, and the major operations performed were compared with operations for ulcerative colitis in the Lothians' Surgical Audit. Fourteen of the 37 patients had a total of 26 operations (15 major, 11 minor). Sixteen per cent had major surgery within 5 years of onset of symptoms, and the types of operation were similar to those recorded in Lothians' Surgical Audit. Operation rate was significantly lower than that for a parallel cohort of patients with Crohn's disease. With a mean follow-up of 7.4 years, seven (19 per cent) patients have a permanent stoma and there has been one death.

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Data was collected from patients with colonic or rectal tumours undergoing potentially curative surgery. Univariate analysis showed an association between perioperative transfusion with plasma and the earlier recurrence of tumour. Allowing for possible confounding factors the relative risk of recurrence for patients receiving plasma was 2.44 (95 per cent confidence interval = 1.10-5.46, P = 0.041) and for patients receiving whole blood or plasma, it was 2.39 (95 per cent confidence interval = 1.19-4.83, P = 0.021). The risk of recurrence for those receiving a transfusion of plasma was, therefore, more than twice that of those not given it. We were unable to demonstrate an independent harmful effect of transfusion with packed cells. These data suggest that the plasma protein, rather than the cellular component of whole blood, mediates the accelerated tumour recurrence.

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