Rectal mucosal prolapse syndrome as an unusual gastrointestinal manifestation of Sjögren's syndrome: a case report.

INTRODUCTION: Rectal mucosal prolapse syndrome, histologically characterized by fibromuscular obliteration in the lamina propria, hyperplastic glands and thickened muscularis mucosa, causes rectal bleeding. Sjögren's syndrome is an autoimmune exocrinopathy that chiefly destroys the salivary and lacrimal glands by lympho-plasmacytic infiltration. Although various gastrointestinal manifestations have been reported in patients with Sjögren's syndrome, there have not been to our knowledge any case reports to date of rectal mucosal prolapse syndrome in association with Sjögren's syndrome. CASE PRESENTATION: A 68-year-old Japanese woman with Sjögren's syndrome and long-term constipation consulted our hospital because of rectal bleeding. Because of dysphagia and xerostomia, she had consistently refused recommendations to take oral medicines including cathartics. Therefore, she frequently strained excessively during defecation. Colonoscopy and radiological examinations disclosed eroded flat protrusions of the rectum. Microscopic examination demonstrated inflamed mucosa with elongated tortuous glands and fibromuscular obliteration. Based on these findings, a diagnosis of rectal mucosal prolapse syndrome was made. Prohibition of straining during defecation and sulfasalazine suppository use were effective. CONCLUSION: This case highlights the importance of defecation control in patients with Sjögren's syndrome. In the case presented, rectal mucosal prolapse syndrome following long-term excessive straining during defecation caused rectal bleeding. Clinicians should consider rectal mucosal prolapse syndrome as a gastrointestinal manifestation of Sjögren's syndrome.

Differential expression of leukocyte functions associated antigen-1 (LFA-1) on peripheral blood mononuclear cells in patients with Crohn's disease.

BACKGROUND: The leukocyte function associated antigen-1 (LFA-1) intracellular adhesion molecule-1 pathway is presumed to play a pivotal role in the perpetuation of inflammatory bowel disease. We aimed to elucidate the effect of 2 different therapies on LFA-1 expression in patients with Crohn's disease (CD) and correlate LFA-1 expression with disease activity. METHODS: In all, 30 patients with active CD were recruited for the present investigation. Eleven patients were treated with infliximab and 19 patients with total parenteral nutrition. The clinical activity and the expression of LFA-1 in peripheral blood mononuclear cells were assessed prior to and 4 weeks after treatment. Clinical activity was determined by measuring the Crohn's Disease Activity Index and LFA-1 expression was measured by mean fluorescence intensity (MFI) under fluorescence-activated cell sorter analysis. RESULTS: In each treatment group the clinical disease activity index decreased significantly 4 weeks after treatment. In patients treated with infliximab, LFA-1 expression decreased significantly (mean MFI decreased from 1983 to 1487, P < 0.05). However, LFA-1 expression remained unchanged in the total parenteral nutrition group (mean MFI elevated from 1684 to 1902, P > 0.05). CONCLUSIONS: The mechanism of therapeutic action on CD is different between infliximab and total parenteral nutrition.

[Nonsteroidal anti-inflammatory drug-induced enteropathy and chronic nonspecific multiple ulcers of the small intestine].

With the development of double balloon endoscopy and video-capsule endoscopy, it has become inevitable for gastroenterologist to diagnose small intestinal ulcers accurately. Chronic nonspecific multiple ulcers of the small intestine (CNSU) and nonsteroidal antiinflammatory drugs-induced enteropathy (NSAIDs-enteropathy) share common clinicopathologic features characterized by histologically nonspecific ulcers and persistent blood loss. In addition, the two disorders had common enteroscopic findings, namely, circular ulcers and concentric stenoses. However, CNSU is distinctive of NSAIDs-enteropathy with respect to intractable ulcers of various configurations. In consideration of widespread use of NSAIDs, a strategy for the prevention of NSAIDs-enteropathy should be examined. Also, much more cases of CNSU should be analyzed to establish the pathophysiology of the disease.

Microcirculatory changes in experimental mesenteric longitudinal ulcers of the small intestine in rats.

Rats receiving intracolonic administration of indomethacin develop longitudinal ulcers on the mesenteric side of the small intestine that are similar to those seen in the acute phase of Crohn's disease. To investigate the causative role of microcirculatory disturbances and to elucidate the therapeutic effect of antioxidants on this enteropathy in rats, we serially evaluated changes in regional blood flow of the small intestine using laser Doppler perfusion imaging and the colored microsphere injection method. Both methods disclosed stepwise hyperperfusion limited to the mesenteric side of the small intestine following transient ischemia during the initial 30-60 minutes. In addition, both a radical scavenger and a radical production inhibitor significantly ameliorated the mesenteric longitudinal ulcers. We concluded that ischemia-reperfusion on the mesenteric side accompanying excessive production of radicals might be strongly involved in indomethacin-induced longitudinal ulcers of the small intestine in rats.

Blockade of tumor necrosis factor-alpha-converting enzyme improves experimental small intestinal damage by decreasing matrix metalloproteinase-3 production in rats.

OBJECTIVE: Tumor necrosis factor (TNF)-alpha-converting enzyme (TACE), which has been purified, regulates maturity of TNF-alpha. Matrix metalloproteinases (MMPs) play a key role in various inflammatory conditions. The incidence of intestinal damage has increased, but the mechanism and treatment have not been well understood. The purpose of this study was to investigate the roles of TACE and MMP in indomethacin (Indo)-induced intestinal damage as well as the therapeutic effects of TACE inhibitor and selective MMP inhibitor (sMMPi) on this intestinal damage in rats. MATERIAL AND METHODS: In the first experiment, serial changes in intestinal ulcers and the production of MMP were investigated. In the second experiment, we assessed the effect of three TACE and/or MMP inhibitors and the production of TNF-alpha, TACE, MMP-3, -9 and tissue inhibitor of MMP (TIMP)-1. The rats were divided into five groups: a control group, and four groups that received Indo alone, Indo plus TACE inhibitor (GM6001), Indo plus a selective MMP-3 inhibitor and Indo plus an MMP-9/13 inhibitor, respectively. RESULTS: MMP-3 was overexpressed at 24 h after Indo administration, when intestinal injury was most prominent macroscopically and microscopically. GM6001 significantly decreased ulcer severity and suppressed MMP-3 in a dose-dependent fashion. The selective MMP-3 inhibitor dose-dependently ameliorated intestinal damage to the same degree as GM6001, but the MMP-9 inhibitor had no effect on the injury. CONCLUSIONS: MMP-3 inhibition ameliorates intestinal damage without apparently affecting either TNF-alpha or TACE production and the dose-response curve suggests that the beneficial effect of the so-called TACE inhibitor is actually mainly mediated via MMP-3 inhibition rather than TNF-alpha inhibition.

Endoscopic features of chronic nonspecific multiple ulcers of the small intestine: comparison with nonsteroidal anti-inflammatory drug-induced enteropathy.

Chronic nonspecific multiple ulcers of the small intestine (CNSU) and nonsteroidal anti-inflammatory drug-induced enteropathy (NSAID-enteropathy) share common clinicopathologic features characterized by histologically nonspecific ulcers and persistent blood loss. The aim was to compare enteroscopic findings between CNSU and NSAID-enteropathy. Four patients with CNSU and five patients with NSAID-enteropathy were examined by enteroscopies. The site of involvement was heterogeneous in NSAID-enteropathy, while the ileum was the predominant site in CNSU. Three patients with NSAID-enteropathy and all four patients with CNSU had concentric stenosis. Circular ulcers were found in all five patients with NSAID-enteropathy and in three patients with CNSU. Active ulcer was seen in only two patients with NSAID-enteropathy. In contrast, all four patients with CNSU had active ulcer. These findings suggest that in patients with persistent GI bleeding and enteroscopically active small intestinal ulcers, CNSU, as well as NSAID-enteropathy, should be considered.

Treatment of ulcerative colitis patients by long-term administration of germinated barley foodstuff: multi-center open trial.

Germinated barley foodstuff (GBF), which mainly consists of dietary fiber and glutamine-rich protein, is a prebiotic for ulcerative colitis (UC). In our previous study, we carried out a clinical trial of GBF with mildly to moderately active UC patients and showed that GBF treatment was able to attenuate the symptoms of UC in a relatively short-term. The aim of this study was to investigate the efficacy of long-term administration of GBF in the treatment of UC in a multi-center open trial. Twenty-one patients with mildly to moderately active UC received 20-30 g of GBF for 24 weeks in an open-label protocol while baseline treatments (5-amino-salicyrate compounds and/or steroids) were continued. The response to the GBF treatment was evaluated using a clinical scoring and after 24 weeks of observation, the GBF group showed a significant decrease in clinical activity index (especially, the degree of visible blood in stools and the presence of nocturnal diarrhea) compared with the control group (p<0.05). No side effects related to GBF were observed. In conclusion, GBF can reduce the clinical activity of UC over long-term as well as short-term administration. Nutraceutical GBF therapy may have a place in long-term management of UC, but controlled studies are needed to demonstrate its efficacy in the treatment of this disorder.

Treatment of ulcerative colitis by feeding with germinated barley foodstuff: first report of a multicenter open control trial.

BACKGROUND: Germinated barley foodstuff (GBF) is a prebiotic foodstuff that effectively increases luminal butyrate production by stimulating the growth of protective bacteria. In the first pilot study, GBF has been shown to reduce both clinical activity and mucosal inflammation in ulcerative colitis (UC). The aim of this study was to investigate the efficacy of GBF in the treatment of UC in a multicenter open control trial. METHODS: Eighteen patients with mildly to moderately active UC were divided into two groups using a random allocation protocol. The control group (n = 7) were given a baseline anti-inflammatory therapy for 4 weeks. In the GBF-treated group (n = 11), patients received 20-30 g GBF daily, together with the baseline treatment, for 4 weeks. The response to the treatments was evaluated clinically and endoscopically. Fecal microflora were also analyzed. RESULTS: After 4 weeks of observation, the GBF-treated group showed a significant decrease in clinical activity index scores compared with the control group (P < 0.05). No side effects related to GBF were observed. GBF therapy increased fecal concentrations of Bifidobacterium and Eubacterium limosum. CONCLUSIONS: Oral GBF therapy may have the potency to reduce clinical activity of UC. We believe that these results support the use of GBF administration as a new adjunct therapy for UC.