Jaime Vilaseca

Dietary inulin improves distal colitis induced by dextran sodium sulfate in the rat

OBJECTIVES:Inulin stimulates intracolonic generation of butyrate and growth of lactic acid bacteria. This study investigated whether inulin protects against colitis.METHODS:Rats with dextran sodium sulfate colitis received inulin either orally (1% in drinking water, or 400 mg/day) or by enema. Matched groups received vehicle. In addition, fecal water obtained from inulin-fed rats was administered by enema to rats with colitis and compared with fecal water from control rats. Finally, rats with colitis received daily enemas of either butyrate (at 40 or 80 mmol/L) or vehicle. Inflammation was assessed by eicosanoid asssay in rectal dialysates and MPO activity in colonic tissue. Mucosal lesions were blindly scored by microscopic examination. Luminal pH was measured from cecum to rectum by a surface microelectrode.RESULTS:Oral inulin prevented inflammation, as evidenced by lower lesion scores (p < 0.05), decreased release of mediators (p < 0.05), and lower tissue MPO (p < 0.05) as compared with controls. Inulin induced acidic environment (pH <7.0) from cecum to left colon and increased counts of lactobacilli. Fecal water from inulin-fed rats also reduced scores (p < 0.05) and inflammation (p < 0.05). However, inulin or butyrate enemas had no effect.CONCLUSIONS:Oral inulin reduces the severity of dextran sodium sulfate colitis. The effect seems to be mediated by modification of the intracolonic milieu.

Influence of inflammatory bowel disease on different dimensions of quality of life.

Objective To establish the impairment of different dimensions of quality of life in inflammatory bowel disease (IBD). Design Prospective observational study. Participants 289 patients [160 with ulcerative colitis (UC) and 129 with Crohns disease (CD)]. Measures Health-related quality of life was assessed by means of the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Psychological General Well Being Index (PGWBI). Results In active IBD, all dimensions of the quality of life scored significantly lower than in inactive IBD, indicating a poor quality of life. Social impairment was the least impaired dimension of the IBDQ in active UC and CD, compared with digestive and systemic symptoms. In inactive IBD, the systemic symptoms domain received the lowest score (P < 0.01). In a subgroup of 22 patients studied before and after remission, emotional function was the most impaired dimension after achieving remission. The Psychological General Well Being Index was significantly impaired in active UC [78.5 (range 64–89)] and CD [76.5 (range 69–97)] relative inactive IBD [104 (range 93–111)] vs 106 (95–113), respectively;P < 0.05]. Conclusions Quality of life is impaired in IBD. During relapse, clinicians should pay attention to digestive symptoms and psychological distress. In remission, they should be sensitive to systemic symptoms.

Participation of thromboxane and other eicosanoid synthesis in the course of experimental inflammatory colitis

Eicosanoids, as modulators of inflammation, may be involved in the pathogenesis of inflammatory bowel disease. We investigated their potential role in a rat model of chronic granulomatous colonic inflammation induced by trinitrobenzene sulphonic acid. Luminal eicosanoid release was quantified in vivo using a dialysis bag placed into the distal colon. We tested the effect of drugs known to modify inflammatory activity or arachidonic acid metabolism. Three days after intracolonic injection of trinitrobenzene sulphonic acid at different dose levels, the dialysates showed a highly significant increase of prostaglandin E2, 6-keto-prostaglandin F1 alpha, thromboxane B2 (TXB2), and leukotriene B4, compared with levels in controls not subjected to the toxic agent. Remarkably, the release of TXB2 continued to increase during the stage of chronic inflammation (up to day 21), whereas the levels of the remainder eicosanoids declined. Treatment with prednisone or 5-aminosalicylic acid reduced TXB2 levels in the chronic stage of the inflammatory disease and improved the morphological damage as assessed macroscopically and histologically. Moreover, two selective thromboxane synthetase inhibitors, OKY 1581 and R70416, significantly reduced the development of chronic inflammatory lesions in the colon while inhibiting the release of TXB2. Our results indicate that (1) luminal release of thromboxane increases in the chronic stage of colonic inflammation, (2) anti-inflammatory treatment reduces tissue damage and thromboxane release, and (3) selective thromboxane synthetase inhibition improves the course of the disease in our experimental model.

Outcome of patients with Ischemic colitis: Review of fifty-three cases

PURPOSE: Ischemic colitis is a disease of elderly patients and includes a wide clinical spectrum ranging from mild to severe forms. Some patients may develop complications. Management of this disorder depends on disease severity. Our aim was to review the clinical characteristics of patients diagnosed of ischemic colitis and analyze predictive factors of poor prognosis. METHODS: This study is a retrospective analysis of 53 cases of ischemic colitis (33 men, 20 women), 35 with moderate and 18 with severe forms, respectively. Clinical characteristics, diagnostic procedures, segment of colon involved and long-term evolution after discharge were analyzed. RESULTS: Hypertension (51 percent) was the main risk factor associated with ischemic colitis. Clinical presentation did not differ between groups, except for peritonitis which was present only in the severe group. Colonoscopy and histologic studies were the most used diagnostic procedures (90 percent). Peripheral vasculopathy (P < 0.01) and right colonic involvement (P < 0.001) were risk factors for severe outcome. Five patients died during admission. Among these, the right colon was affected in four (80 percent). No patient in either group developed chronic ischemic colitis during follow-up. CONCLUSION: Ischemic colitis usually runs a benign course after acute colonic insult. Peripheral vasculopathy and right colonic involvement are associated with severe forms of ischemic colitis.

Validation of the Spanish Version of the Inflammatory Bowel Disease Questionnaire on Ulcerative Colitis and Crohn’s Disease

The objective of this study is to validate the Spanish translation of the Inflammatory Bowel Disease Questionnaire (SIBDQ) on ulcerative colitis and Crohn’s disease by assessing its convergence validity, discriminatory power, reliability and sensitivity to change. For that purpose, 211 patients with inflammatory bowel disease (116 with ulcerative colitis and 95 with Crohn’s disease) completed the SIBDQ, the Psychological General Well-Being Index and the EuroQol. SIBDQ was repeated in those patients who remained in stable remission and in those with changes in clinical activity. Clinical activity was assessed by the Rachmilewitz and Harvey-Bradshaw indices. Correlations among scores of SIBDQ, EuroQol, Psychological General Well-Being Index and clinical indices of activity were all positive and comparable for both diseases (r = –0.50 to r = –0.70, p < 0.01). Analysis of variance showed that SIBDQ discriminates between different clinical degrees of activity. Cronbach’s α was 0.96 in ulcerative colitis and Crohn’s disease. SIBDQ was also highly reliable when it was repeated in clinically stable patients with ulcerative colitis (intraclass correlation coefficient = 0.82) and Crohn’s disease (intraclass correlation coefficient = 0.86). SIBDQ was sensitive to clinical changes in ulcerative colitis and in Crohn’s disease, whether patients entered remission (effect size –1.88 and –1.81, respectively) or relapsed (effect size 1.70 and 8.04, respectively). In conclusion, the Spanish version of the IBDQ has proven to be a valid, reliable and sensitive instrument to detect clinical changes in patients with ulcerative colitis and Crohn’s disease.

Impact of surgery for Crohn's Disease on health-related quality of life

OBJECTIVE:When patients with Crohns disease (CD) express concerns about their disease, they emphasize worries about surgery. However, most studies about the impact of surgery in CD on health-related quality of life (HRQOL) have compared postsurgical changes on HRQOL relative to HRQOL before surgery, not taking into account the influence of CD activity on HRQOL. Our aim was to assess whether surgical treatment of CD modifies HRQOL, compared with inactive CD, active CD, or healthy controls.METHODS:Outcomes of 29 CD patients in remission with a previous bowel resection were compared with those from 42 clinically active CD patients and 48 patients with medically induced remission. A reference control group of 63 healthy individuals was also studied. HRQOL was measured by the Inflammatory Bowel Disease Questionnaire (IBDQ), the Psychological General Well Being Index (PGWBI), and the EuroQol.RESULTS:Active CD patients scored the lowest on the IBDQ. Both operated and nonoperated inactive CD patients had lower HRQOL scores than controls in overall IBDQ and in all five domains. However, neither global score, digestive, systemic, emotional, social, or functional dimensions differed significantly between operated and nonoperated inactive CD patients. PGWBI and the visual analog scale of the EuroQol were also similar in both groups of inactive CD patients (103 [range, 94–107] vs 103 [97–106] and 90 [73–87] vs 82 [76–84]), but significantly higher than in active CD.CONCLUSIONS:HRQOL is impaired in active CD, and improves during remission irrespective of whether it had been achieved medically or surgically. Our results suggest that to improve HRQOL it is more important to achieve remission than the approach, drugs or surgery, chosen.

Long-term efficacy of octreotide in the prevention of recurrent bleeding from gastrointestinal angiodysplasia.

OBJECTIVES:Preliminary studies suggested that octreotide may be therapeutic in bleeding angiodysplasia. Our aim was to investigate the efficacy of long-term octreotide therapy in the prevention of rebleeding from gastrointestinal angiodysplasia.METHODS:A cohort of 32 patients diagnosed with bleeding from angiodysplasia was treated with octreotide 50 μ 12 h subcutaneously for a 1–2 yr period. This cohort was compared with an external control group (38 patients who had received placebo [1 tablet/day] in a concurrent randomized clinical trial for the same period.RESULTS:Two patients of the octreotide group were lost to follow-up. Treatment failure occurred in seven of 30 (23%) patients in the octreotide group and in 17 of 35 (48%) in the placebo group (three dropouts before first visit) (P = 0.043). The actuarial probability of remaining free of rebleeding at 1 and 2 yr of follow-up was 77% and 68%, respectively, for the octreotide group and 55% and 36%, respectively, for the placebo group (log rank P = 0.030). Multivariate proportional hazards-regression analysis showed that octreotide therapy and previous bleeding episodes were positive and negative predictors of efficacy, respectively. No significant differences between the groups were observed according to number of bleeding episodes (0.4 ± 0.7 vs 0.9 ± 1.5, P = 0.070) and transfusion requirements (1.1 ± 2.6 vs 0.7 ± 1.5 units); however, iron requirements were lower in the octreotide than in the placebo group (22 ± 62 vs 166 ± 267 units; P < 0.001). Likewise, major adverse events (1 vs 1) and mortality (0 vs 1) were similar between groups.CONCLUSIONS:This study suggests that octreotide treatment may be beneficial in preventing rebleeding from gastrointestinal angiodysplasia.

Efficacy of intravenous cyclosporine for steroid refractory attacks of ulcerative colitis

The use of cyclosporine in refractory ulcerative colitis (UC) is still controversial. An 8-year-long retrospective review open-label treatment with intravenous cyclosporine in 21 patients with steroid-refractory UC is therefore in order. Intravenous cyclosporine, 5 mg/kg-1 day, was added to ongoing drug therapy. Those who responded were switched to oral cyclosporine for a mean 8.4-month period, and steroids were discontinued when possible. Sixteen out of 21 patients improved (76%). Mean latency time to onset of improvement was 9 days. Five did not improve: three underwent urgent surgery, one was switched to methotrexate, and the remainder died. While on oral cyclosporine, 10 out of 16 maintained remission and seven could discontinue steroids, five relapsed, and one went on continuous mild activity. One patient died of a Pneumocystis carinii pneumonia, while in remission. Five reversible episodes of hepatobiliary toxicity were recorded. Intravenous cyclosporine effectively and rapidly induces improvement of acute steroid-refractory flare-ups of UC and helps to prevent urgent surgery. However, major adverse events may limit its usefulness.

Therapeutic Effect of Phenantroline in Two Rat Models of Inflammatory Bowel Disease

Background: Phenantroline is a zinc-chelator that inhibits biological activities of matrix metalloproteinases (MMPs). Over-expression of MMPs can accelerate tissue destruction and disrupt subsequent tissue repair. The effects of phenantroline in two rat models of inflammatory bowel disease (IBD) are evaluated: transmural colitis induced by trinitrobenzensulphonic acid (TNBS) and distal colitis caused by dextran sulphate sodium (DSS). Methods: Transmural colitis was induced by TNBS in two groups of 15 rats each, and distal colitis was induced by DSS in two other groups of 15 rats each. Phenantroline was administered by oral gavage at 20 mg kg -1 day -1 to the test groups, whereas matched control groups received oral vehicle. On the last day of dosing, rats were subjected to intracolonic dialysis under anaesthesia for assessment of luminal eicosanoid release (PGE 2 , TXB 2 and LTB 4 ) and euthanized. Colons were removed and lesions were blindly scored according to macroscopic and histological scales. Myeloperoxidase (MPO) activity was measured in homogenates of colonic tissue. Results: In the TNBS model, phenantroline treatment significantly reduced colonic strictures; in the DSS model, phenantroline significantly decreased scores of epithelial injury. In both models, the levels of PGE 2 , TXB 2 and LTB 4 and tissue MPO were not significantly altered. Conclusions: Although phenantroline did not modify the activity of inflammatory mediators, this compound substantially reduced intestinal injury associated with tissue remodelling.BACKGROUND Phenantroline is a zinc-chelator that inhibits biological activities of matrix metalloproteinases (MMPs). Over-expression of MMPs can accelerate tissue destruction and disrupt subsequent tissue repair. The effects of phenantroline in two rat models of inflammatory bowel disease (IBD) are evaluated: transmural colitis induced by trinitrobenzensulphonic acid (TNBS) and distal colitis caused by dextran sulphate sodium (DSS). METHODS Transmural colitis was induced by TNBS in two groups of 15 rats each, and distal colitis was induced by DSS in two other groups of 15 rats each. Phenantroline was administered by oral gavage at 20 mg kg(-1) day(-1) to the test groups, whereas matched control groups received oral vehicle. On the last day of dosing, rats were subjected to intracolonic dialysis under anaesthesia for assessment of luminal eicosanoid release (PGE2, TXB2 and LTB4) and euthanized. Colons were removed and lesions were blindly scored according to macroscopic and histological scales. Myeloperoxidase (MPO) activity was measured in homogenates of colonic tissue. RESULTS In the TNBS model, phenantroline treatment significantly reduced colonic strictures; in the DSS model, phenantroline significantly decreased scores of epithelial injury. In both models, the levels of PGE2, TXB2 and LTB4 and tissue MPO were not significantly altered. CONCLUSIONS Although phenantroline did not modify the activity of inflammatory mediators, this compound substantially reduced intestinal injury associated with tissue remodelling.

Intravenous cyclosporine for steroid-refractory attacks of Crohn's disease. Short- and long-term results.

A prospective, open trial was conducted to test whether i.v. cyclosporine was effective in the treatment of refractory Crohns disease. Eight patients with acute steroid-refractory attacks were included. Intravenous cyclosporine, 5 mg/kg/day, was added to ongoing drug therapy. Patients who responded were then switched to oral cyclosporine for a mean 2.6-month period, and steroids were discontinued when possible. Six patients improved, with a mean latency time to onset of improvement of 9 days. Two did not improve, and both underwent urgent operation. On oral cyclosporine, five patients maintained remission and discontinued steroids, whereas one relapsed and underwent surgery. After discontinuation of oral cyclosporine, the five remaining patients relapsed, and two underwent surgery. One reversible episode of hepatobiliary toxicity and one of gastrointestinal intolerance were recorded. We conclude that i.v. cyclosporine effectively and rapidly induces improvement of acute steroid-refractory flare-ups of Crohns disease, but after discontinuation relapse is to be expected.