Evidence of Epstein-Barr virus infection in ulcerative colitis

BACKGROUND AND AIM: The aetiology of ulcerative colitis is still controversial, however, recent studies have emphasised the possible role of infectious agents or ingested substances and their breakdown products, which might activate immune-mediated mechanisms eventually leading to tissue damage. Aim of this investigation was to ascertain the occurrence and the potential role of Epstein-Barr virus infection in large bowel mucosa of ulcerative colitis patients. PATIENTS AND METHODS: Twenty-three biopsies and six total colectomies from 17 patients were analysed for the expression of Epstein-Barr virus proteins and RNAs. Polymerase chain reaction experiments were also carried out to detect Epstein-Barr virus DNA. For comparison, ten biopsies from patients with Crohn's disease, ten biopsies from patients with different types of colitis, seven biopsies and five surgical margins of normal colonic mucosa from the small and large bowels were studied (controls). RESULTS: Six biopsies and four colectomies from seven ulcerative colitis patients showed scattered lymphocytes expressing nuclear EBER 1-2 and harbouring polymerase chain reaction-amplifiable Epstein-Barr virus-DNA. In some cases, linear viral DNA (typical of lytic Epstein-Barr virus infection) was also found. Epithelial cells were invariably negative in all cases. All control tissues from non-ulcerative colitis patients were also invariably non-reactive. CONCLUSION: Evidence of Epstein-Barr virus infection in the mucosal inflammatory cells of ulcerative colitis patients suggests a possible role of this virus in the chronicity of ulcerative colitis.     

A new prebiotic from germinated barley for nutraceutical treatment of ulcerative colitis

A germinated barley foodstuff (GBF) containing glutamine-rich protein and hemicellulose-rich fiber was made from brewer's spent grain, by physical isolation. Our previous studies demonstrated that GBF supported maintenance of epithelial cell populations, facilitated epithelial repair, and suppressed epithelial nuclear factor kappaB-DNA-binding activity through generating increased short-chain fatty acid (especially butyrate) production by luminal microflora, which includes Bifidobacterium and Eubacterium, thereby preventing experimental colonic injury. The fiber fraction also modulates stool water content because of its high water-holding capacity. The patients with mild to moderate active ulcerative colitis who had been unresponsive to or intolerant of standard treatment received 20-30 g GBF, feeding daily in a non-randomized, open-label fashion. At 4 weeks, this treatment resulted in a significant clinical and endoscopic improvement. The improvement was associated with an increase in stool butyrate concentrations. These results indicate that GBF feeding is a potentially new, attractive prebiotic treatment in patients with ulcerative colitis. The potency of GBF on modulating microflora, as well as the high water-holding capacity, may play an important role in treatment and prolongation of remission in ulcerative colitis.     

Surgery for ulcerative colitis in 1,000 patients

Background and aims  

Ileal pouch–anal anastomosis (IPAA) has become the standard treatment for patients with ulcerative colitis (UC) who ultimately require a colectomy. Herein, we report results of our 24-year experience with that surgical method at our hospital.     

Infliximab for patients with refractory ulcerative colitis

Conventional treatment options for patients with severe corticosteroid-refractory ulcerative colitis (UC) include intravenous cyclosporine, which is frequently limited by toxicity, or colectomy. The efficacy of infliximab was investigated in the treatment of 16 patients with severely active UC refractory to conventional therapy; 7 of these patients were considered for colectomy pending medical failure. All patients received a single infusion of infliximab, 5 mg/kg; 6 of 16 patients (38%) received a second infusion approximately 5 months later. Efficacy was assessed by clinical response (defined as the lack of symptoms) as well as endoscopic and histologic outcomes. Clinical, endoscopic, and histologic improvement was observed in 14 of 16 patients (88%) after treatment with infliximab. Surgery was avoided in six of seven surgical candidates (86%). Clinical remission was maintained in 14 of 16 patients (88%) for > or = 4 months, and 4 of 16 patients (25%) for 7-10 months. Most of the treated patients were completely withdrawn from corticosteroid therapy. Treatment with infliximab induced endoscopic remission at 30 days and a significant improvement from baseline in mean histologic score (p < 0.001). In conclusion, infliximab improved clinical, endoscopic, and histologic outcomes in patients with severely active UC refractory to conventional therapy, allowing corticosteroid sparing and reducing the need for colectomy.     

Testing nicotine gum for ulcerative colitis patients

Epidemiologic studies have documented an association between nonsmoking and ulcerative colitis and case reports have demonstrated that symptoms improve with smoking and worsen with removal of a nicotine source. A double-blind randomized crossover trial for individual ulcerative colitis patients (single-patient trial, or Nof 1 clinical trial) was designed to study the safety, patient acceptance, and the effectiveness of nicotine gum in improving patient symptoms and proctoscopic appearance of involved colon. Seven nonsmoking patients chewed up to 10 squares/day (20 mg) of nicotine gum or placebo gum for two weeks. Therapy was crossed-over every two weeks over the eight-week trial. Effectiveness was judged from comparisons between nicotine-gum and placebo-gum periods of patient self-reported symptoms at the conclusion of each two-week period using visual analog scales and proctoscopic appearance using ordered categorical scales. Three of seven patients, all three of whom were former smokers, demonstrated sufficient improvement without adverse effects to warrant institution of nicotine gum into their drug treatment regimens. Three patients demonstrated an uncertain response, despite tolerating the drug, and have not had nicotine gum added to their regimens. One patient could not tolerate the medication and was withdrawn from the study. No serious side effects were noted. We conclude that a randomized trial for an individual patient is a useful method for evaluating treatment regimens for ulcerative colitis and that nicotine gum may be effective therapy for individual patients with ulcerative colitis who demonstrate an objective response with few adverse effects.Dr. Silverstein is a Henry J. Kaiser Family Foundation Clinical Scholar in General Internal Medicine.Research supported in part by the Gastrointestinal Research Foundation Junior Board.     

Induction of experimental ulcerative colitis by Fusobacterium varium isolated from colonic mucosa of patients with ulcerative colitis

BACKGROUND: Bacteria are implicated in certain forms of model chronic colitis but the identity and role of bacteria in human ulcerative colitis (UC) are uncertain. AIMS: To isolate pathogenic bacteria from inflamed mucosa of patients with UC, to examine whether the bacteria have a toxin to Vero cells, and to determine whether the toxin induces UC-like lesions in animals. METHODS: Bacteria were isolated from UC patients and supernatants from cultures were filtered and tested for cytotoxicity to Vero cells. Bacterial cells producing the cytotoxic supernatants were examined by polymerase chain reaction for verotoxin genes. Culture supernatants of cytotoxic strains were examined by high performance liquid chromatography for organic acid concentrations. Mice were given enemas containing organic acid at the mean concentration in the supernatants of cytotoxic strains to ascertain whether colonic lesions appear in UC. RESULTS: Only supernatants from cultures of Fusobacterium varium killed Vero cells. Bacterial cells lacked verotoxin genes. Bacterial culture supernatants contained high concentrations of n-butyric acid and the mean concentration (32 mmol/l) was cytotoxic to Vero cells. Twenty four hours after mice were given enemas containing either butyric acid or F varium culture supernatants, colonic ulcers with crypt abscesses, inflammatory cell infiltration, and apoptotic changes were observed. CONCLUSIONS: Butyric acid in culture supernatants from cultures of F varium caused UC-like lesions in mice. This study indicates that F varium may be one of the elusive pathogenic factors in UC.     

Infliximab for hospitalized patients with severe ulcerative colitis

To evaluate the efficacy of infliximab in hospitalized ulcerative colitis (UC) patients refractory to intravenous corticosteroids. Treatment options for steroid-refractory UC patients are limited and include cyclosporine and colectomy. Although two recent studies (ACT I/II) demonstrate a benefit from infliximab in outpatients with moderate to severely active UC, the utility of infliximab in severe i.v. steroid-refractory UC is less clear. We report our open-label experience with infliximab in hospitalized UC patients at the University of Pittsburgh Medical Center. All hospitalized UC patients who had received infliximab were identified. Age, sex, extent of UC, duration of disease, concomitant medication, hospital course, and response to infliximab were recorded. Response to infliximab was defined as avoidance of colectomy and cessation of corticosteroids. There were 12 UC inpatients refractory to intravenous corticosteroids and subsequently treated with infliximab. Nine of the 12 patients (75%) failed to respond to infliximab and required a colectomy; median time to colectomy was 3 months. Three patients (25%) did respond to infliximab and were able to withdraw from corticosteroids. In this open-label analysis, infliximab was not effective for the majority of UC patients refractory to intravenous corticosteroids. Whether earlier use of infliximab would prevent the need for hospitalization and colectomy is uncertain.     

Microaggregate of immunostained macrophages in noninflamed gastroduodenal mucosa: a new useful histological marker for differentiating Crohn's colitis from ulcerative colitis

OBJECTIVE: In 10% of cases it may be difficult to differentiate Crohn's colitis from ulcerative colitis. Distinguishing the two conditions is important because they are distinct entities with different therapeutic implications. Noncaseating granulomas are usually considered diagnostic of Crohn's disease. We previously reported that the presence of a microaggregate of immunostained macrophages within the noninflamed gastroduodenal mucosa was a characteristic finding of Crohn's disease. The aim of this study was to determine whether a microaggregate of immunostained macrophages can be a reliable marker for differentiating Crohn's colitis from ulcerative colitis. METHODS: We investigated the presence of microaggregates of immunostained macrophages and epithelioid cell granulomas in biopsy specimens taken from the noninflamed gastroduodenal mucosa of 22 known Crohn's colitis patients and 23 established ulcerative colitis patients. The incidence of microaggregates and granulomas was compared between these two groups. RESULTS: Microaggregates and granulomas were detected only in the Crohn's colitis patients. In addition, the presence of microaggregates was more frequent than that of granulomas in Crohn's colitis patients (54.5% and 18.2%, respectively, 95% confidence interval for the difference: 10.0-62.7%). CONCLUSION: Detecting a microaggregate of immunostained macrophages in a biopsy specimen taken from noninflamed gastroduodenal mucosa seems to be a useful method for differentiating Crohn's colitis from ulcerative colitis.     

Retrograde distribution of a new 5-aminosalicylic acid enema in patients with ulcerative colitis.

Retrograde colonic distribution of a new 4 g 5-aminosalicylic acid enema (mesalazine) was investigated in seven patients with ulcerative colitis, five of whom were in remission. The enema was labeled with 99m-technetium and imaged by a gamma camera. A median of 86 percent (range 57-90) of the enema had spread beyond the rectum during the first two hours after administration. In four of the five examined patients with left-sided ulcerative colitis, the diseased mucosa was covered within the first 4 hours. In the fifth patient, with involvement of the descending colon, the enema did not spread beyond the very tortuous sigmoid colon 4 or even 8 hours after enema administration.