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Long-term study of TNBS-induced colitis in rats: focus on mast cells.

OBJECTIVE AND DESIGN: To investigate the severity and duration of colitis induced by two different doses of 2,4,6-trinitrobenzenesulfonic acid (TNBS) and the changes in mast cell number in acute inflammation and in the recovery process of colitis. METHODS: Colitis was induced in rats by an enema of TNBS (10 or 30 mg) in 25% ethanol. Macroscopic and histologic changes of the colon, colon weight and mast cell counts were examined at various times (7, 30 and 60 days) after colitis induction. RESULTS: TNBS induced a colonic damage which was dose-related for both severity and time necessary to complete recovery. On day 7 after colitis induction 10 mg TNBS induced macroscopic and microscopic alterations of colonic architecture that completely resolved at day 60. By contrast, 30 mg TNBS induced massive necrosis, thickening of the colon, severe histologic changes that were only partially reversed after two months. Mast cell number in the submucosa and muscularis propria decreased significantly in the acute phase of inflammation (7 days) and slowly increased thereafter, reaching a maximum level (up to about 5-fold) at day 60 after both doses of TNBS. CONCLUSIONS: Present data confirm the ability of TNBS to induce in rats damage to the colon that was dose-dependent for severity and duration. Moreover, these data unravel a different role of mast cells in TNBS-induced colitis: an early degranulation in the acute phase of inflammation and a subsequent accumulation of mast cells in the late phase of the disease, associated with tissue repair.

Animals↗

Use of technetium-tagged white blood cells in patients with Crohn's disease and ulcerative colitis: is differential diagnosis possible?

BACKGROUND: Studies have suggested that scans with technetium-tagged white blood cells (WBC-Tc99m) may be equal to endoscopy in the assessment of extent and activity of inflammatory bowel disease (IBD). OBJECTIVE: We have retrospectively examined the accuracy of WBC-Tc99m scans in differentiating continuous from discontinuous colitis in pediatric IBD. MATERIALS AND METHODS: There were 207 children in the study (96 boys, 111 girls, median age 13 years). This included 29 controls - children with no gastrointestinal disease (NL) who underwent WBC-Tc99m scans for other medical problems. Scans were obtained at 30 minutes and 2-4 hours following injection. Scans were interpreted as showing continuous colitis, discontinuous colitis, or no colitis. RESULTS: In the 77 children with active Crohn's disease (CD) of the colon, the scans revealed discontinuous uptake in 63 children and continuous uptake in 14. In the 29 children with ulcerative colitis (UC), 23 scans showed continuous uptake and 6 revealed discontinuous uptake. Two of these 6 showed focal activity near the appendix, and subclinical appendicitis could not be excluded. Another child was bleeding and the scan could have been misinterpreted as showing small- bowel inflammation. In the last three patients, skip areas were clearly identifiable. In none of these last three patients were the biopsies typical of CD (i. e., no granuloma was identified) nor was inflammation patchy. In summary, of the 106 scans showing inflammation, 6 were classified into the wrong group. CONCLUSION: These data show that WBC-Tc99m scanning can be useful in distinguishing discontinuous from continuous colitis.

Adolescent↗

Allergic colitis: a mimic of Hirschsprung disease.

BACKGROUND: Allergy to cow milk protein is a common cause of gastrointestinal symptoms in infancy. Milk allergy is usually a clinical diagnosis, and thus there have been few reports of the radiographic findings. OBJECTIVE: To describe the barium enema findings of allergic colitis and differentiate them from Hirschsprung disease. Materials and methods. Four infants (age range 7 days-5 weeks) with constipation underwent barium enema to exclude Hirschsprung disease. Radiographic findings were correlated with the pathologic specimens from suction rectal biopsy. RESULTS: All enemas revealed irregular narrowing of the rectum and a transition zone. Rectal biopsies in each case demonstrated ganglion cells and evidence of an allergic colitis, with inflammatory infiltrates in the lamina propria. A diagnosis of milk allergy colitis was made and symptoms resolved after removal of milk from the diet. CONCLUSIONS: Milk allergy is common in infancy. The rectum is a primary target organ, with allergic colitis often diagnosed on clinical grounds alone. However, a child with allergic colitis may be referred to radiology for barium enema, especially if constipation is present. The radiologist should be aware of the unique imaging findings of allergic colitis, so as to avoid confusion with Hirschsprung disease and perhaps an unnecessary rectal biopsy.

Animals↗

Ameliorative effect of IDS 30, a stinging nettle leaf extract, on chronic colitis.

BACKGROUND AND AIMS: Anti-TNF-alpha antibodies are very effective in the treatment of acute Crohn's disease, but are limited by the decline of their effectiveness after repeated applications. The stinging nettle leaf extract, IDS 30, is an adjuvant remedy in rheumatic diseases dependent on a cytokine suppressive effect. We investigated the effect of IDS 30 on disease activity of murine colitis in different models. METHODS: C3H.IL-10-/- and BALB/c mice with colitis induced by dextran sodium sulphate (DSS) were treated with either IDS 30 or water. Mice were monitored for clinical signs of colitis. Inflammation was scored histologically, and faecal IL-1beta and mucosal cytokines were measured by ELISA. Mononuclear cell proliferation of spleen and Peyer's patches were quantified by 3H-thymidine. RESULTS: Mice with chronic DSS colitis or IL-10-/- mice treated with IDS 30 clinically and histologically revealed significantly (p < 0.05) fewer signs of colitis than untreated animals. Furthermore, faecal IL-1beta and mucosal TNF-alpha concentrations were significantly lower (p < 0.05) in treated mice. Mononuclear cell proliferation after stimulation with lipopolysaccharide was significantly (p < 0.001) reduced in mice treated with IDS 30. CONCLUSIONS: The long-term use of IDS 30 is effective in the prevention of chronic murine colitis. This effect seems to be due to a decrease in the Th1 response and may be a new therapeutic option for prolonging remission in inflammatory bowel disease.

Animals↗

Oral budesonide therapy improves quality of life in patients with collagenous colitis.

INTRODUCTION: Collagenous colitis is an idiopathic microscopic colitis characterised by watery diarrhoea. The impact of collagenous colitis on quality of life has not been assessed. Our aim was to assess quality of life in patients with this condition and compare the effect of treatment with budesonide capsules or placebo on this parameter. METHODS: Patients with chronic diarrhoea and histologically-proven collagenous colitis were randomised to receive either budesonide controlled-release capsules (Entocort capsules, AstraZeneca, Lund, Sweden), 9 mg/day, or placebo for 6 weeks. Quality of life was measured using the validated Gastrointestinal Quality of Life Index (GIQLI) at baseline and after 6 weeks. With the GIQLI, scores range from 0 to 144, with higher scores representing better quality of life. RESULTS: Complete quality of life assessment was available in 29 patients (budesonide: n=17; placebo: n=12). At baseline, quality of life was low in patients with collagenous colitis (mean 76). After 6 weeks of treatment, the mean GIQLI score increased significantly in the budesonide group (from 67 to 92, p<0.001), but remained unchanged in the placebo group (86-88). The mean score of the dimensions symptoms (p=0.001), emotional functioning (p=0.003) and physical functioning (p=0.017) increased significantly in the budesonide group compared with the placebo group. A significantly larger proportion of patients in the budesonide group experienced improved stool consistency (p<0.01) and a significant reduction in the mean stool frequency compared with those in the placebo group (p<0.01). CONCLUSION: Quality of life is seriously reduced in patients with collagenous colitis. Six-week treatment with oral budesonide controlled-release capsules significantly improves quality of life and clinical symptoms compared with placebo in these patients.

Administration, Oral↗

An immunocompetent infant with cow's milk allergy and cytomegalovirus colitis.

UNLABELLED: A 5-week-old, severely ill, infant is described with diarrhoea and rectal bleeding, followed by vomiting and dehydration after introduction of a cow's milk formula. A diagnosis of cow's milk allergy was made because of the clinical presentation of an allergic enterocolitis, the rapid improvement after introduction of a hypo-allergenic formula and development of colic directly after rechallenge with cow's milk. Furthermore a highly specific IgE for alpha-lactalbumin strongly supported the diagnosis. Because of recurrent rectal bleeding a limited colonoscopy was performed at the age of 10 weeks. Surprisingly a second diagnosis of histopathologically proven cytomegalovirus (CMV) colitis was made. Extensive immunological screening revealed no signs of immunodeficiency. The child thrived without any treatment for CMV and developed normally. This is the first description of an immunocompetent infant with CMV colitis. CONCLUSION: It cannot be excluded that the allergic colitis facilitated the CMV colitis, or vice versa CMV colitis triggered cow's milk protein induced entero-colitis. Further attention should be given to children with bloody diarrhoea to establish a possible relationship between CMV infection and cow's milk protein allergy.

Colitis↗

Effects of germinated barley foodstuff on dextran sulfate sodium-induced colitis in rats.

Germinated barley foodstuff (GBF), derived from the aleurone and scutellum fractions of germinated barley, is rich in glutamine and low-lignified hemicellulose, and increases mucosal protein, RNA, and DNA content in the intestine when fed to normal rats. The aim of this study was to evaluate the effects of feeding GBF or germinated gramineous seeds on experimental ulcerative colitis. Sprague-Dawley rats that received 3% dextran sulfate sodium in their diets were used as an experimental colitis model. The effects of sulfasalazine, a drug used to treat inflammatory bowel disease, were compared with those of GBF. After rats had consumed diets containing GBF or various aleurone and scutellum fractions, mucosal damage; the content of mucosal protein, RNA, and DNA in the colo-rectum; and serum interleukin-8 and alpha1-acid glycoprotein levels were assessed. GBF and germinated seeds more effectively prevented bloody diarrhea and mucosal damage in colitis compared with controls and rats receiving sulfasalazine, but non-germinated samples did not have a protective effect. GBF increased mucosal protein and RNA content in the colitis model. The consumption of GBF appears to prevent inflammation in a colitis model, and its effect seems to be related to the germination process. GBF and germinated seeds have the potential to serve as nutritional therapy for ulcerative colitis.

Animals↗

Inducible nitric oxide synthase activity in colon biopsies from inflammatory areas: correlation with inflammation intensity in patients with ulcerative colitis but not with Crohn's disease.

Nitric oxide synthase (NOS) activities are responsible for the enzymatic conversion of L-arginine into NO and L-citrulline. Relatively low amounts of NO are produced in intestinal epithelial cells or are released from nerve endings. The effects of NO production are related to the maintenance of epithelial integrity and permeability. A pathological role of an increased NO production has been suggested to play a role in models of experimental colitis. In humans, NOS activity in colon mucosa from patients with ulcerative colitis is clearly increased when compared with the activity of the control group. In contrast, an increase of NOS activity in the colon mucosa from patients with Crohn's disease remains controversial. In the present work, we have measured NOS activity in colon biopsies originating from the control group (n = 16), from patients with ulcerative colitis (n = 23) and Crohn's disease (n = 17) using the radiochemical method of the conversion of L-[guanido-14C] arginine into radioactive L-citrulline. In the control group, NOS activity was mainly of the inducible type (88% of total NOS activity) since it was characterised by its insensibility to the absence of calcium in the assay medium. In colon biopsies originating from patients with ulcerative colitis, inducible NOS activity was increased 3 fold (p < 0.005) and in patients with Crohn's disease, inducible NOS activity was increased 5 fold (p < 0.005). Correlations between NOS activity in colon biopsies and the intensity parameters of the disease i.e. Truelove index, endoscopic score and histological parameters were evidenced in patients with ulcerative colitis. In contrast, in patients with Crohn's disease, the high inducible NOS activity was not correlated with any intensity parameters of the disease. From these data, we concluded that although inducible NOS activity was increased several fold in colon biopsies originating from patients with both ulcerative colitis and Crohn's disease, a correlation between this activity and the severity of bowel inflammation was not found in either cases.

Adult↗

Restorative proctocolectomy for ulcerative colitis complicated by colorectal cancer.

PURPOSE: Restorative proctocolectomy with ileal pouch-anal anastomosis is widely accepted as the procedure of choice for patients requiring surgery for chronic ulcerative colitis. The role of restorative proctocolectomy in the setting of chronic ulcerative colitis complicated by colorectal carcinoma is not clear. This study was undertaken to explore the clinical outcomes of chronic ulcerative colitis patients with coexisting colorectal carcinoma who underwent restorative proctocolectomy. METHODS: A total of 756 patients with chronic ulcerative colitis were followed prospectively after restorative proctocolectomy. Forty-five (5.9 percent) were found to have invasive carcinoma of the colon (n = 31) or rectum (n = 14). These patients were followed with special attention to cancer stage, adjuvant therapy, oncologic outcome, and functional results after restorative proctocolectomy. RESULTS: Twenty-one patients (45.6 percent) had staged surgery (colon, 14; rectum, 7). Twenty-seven patients received adjuvant chemotherapy (colon, 22; rectum, 5). Fourteen patients (51.8 percent) who received chemotherapy were not diverted during this treatment. Two node-positive rectal cancer patients had pelvic radiotherapy: one before restorative proctocolectomy and one after restorative proctocolectomy. Mean time to restoration of intestinal continuity among staged patients did not differ between cancer and noncancer patients. Six patients died of metastatic disease (colon, 3; rectum, 3). Five deaths occurred among patients with Stage III disease (colon, 3/13, 23.1 percent; rectum, 2/3, 66.7 percent). One patient with Stage I cancer at the time of restorative proctocolectomy died. Thirty-nine patients are alive without evidence of disease at a mean interval from surgery of 76.5 months. Thirty-six patients have functioning pelvic pouches. Bowel frequency, continence, and complication rates are similar among restorative proctocolectomy patients with and without cancer. CONCLUSIONS: Restorative proctocolectomy as a single or staged procedure is a viable therapeutic option for selected chronic ulcerative colitis patients with associated colorectal cancers. Prognosis seems to be related to cancer stage. Adjuvant chemotherapy can safely be given to nondiverted patients. Appropriate use of preoperative and postoperative radiotherapy for rectal cancer patients who are otherwise candidates for restorative proctocolectomy is unknown. Long-term functional results for cancer patients are similar to those seen in chronic ulcerative colitis patients without cancer.

Adult↗

Turnbull-Blowhole colostomy for toxic ulcerative colitis in pregnancy: report of two cases.

PURPOSE: Surgical intervention for toxic ulcerative colitis in pregnancy is associated with a high morbidity and mortality for both mother and her fetus. A limited surgical procedure may be desirable to reduce the risk of maternal and fetal mortality. We describe the use of "blowhole" colostomy and loop ileostomy (Turnbull procedure) in the management of toxic dilation of the colon complicating ulcerative colitis in pregnancy. METHODS: The medical records of two pregnant females with toxic ulcerative colitis were reviewed. The presentations, management, and outcomes of these patients and their neonates are described. RESULTS: The Turnbull-Blowhole colostomy and ileostomy was used in the acute management of toxic ulcerative colitis in two pregnant females. Both mothers and neonates had successful outcomes with resolution of the acute process. Completion proctocolectomy and ileal pouch-anal anastomosis was later performed in both patients. CONCLUSIONS: The colonic decompression and fecal diversion procedure provided minimal operative trauma to the mother and fetus and resulted in successful outcome in the management of toxic ulcerative colitis in pregnancy. We believe the procedure is safe, effective, and relatively simple, which may reduce the morbidity and mortality of toxic colitis in pregnancy.

Adult↗

Serologic responses in indeterminate colitis patients before ileal pouch-anal anastomosis may determine those at risk for continuous pouch inflammation.

PURPOSE: Although acute pouchitis after ileal pouch-anal anastomosis is common and easily treated, continuous pouch inflammation seen clinically as chronic, antibiotic-dependent pouchitis, and/or Crohn's disease remains a difficult management problem. Compared with ulcerative colitis, indeterminate colitis patients undergoing ileal pouch-anal anastomosis have a higher incidence of continuous pouch inflammation, which may represent persistent immune reactivity to microbial antigens. Antibody responses to three microbial antigens (oligomannan anti-Saccharomyces cerevisiae, outer membrane porin C of Escherichia coli, and an antigen (I2) from Pseudomonas flourescens) are more commonly seen in Crohn's disease, whereas antibodies to a cross-reactive antigen (perinuclear antineutrophil cytoplasmic antibodies) is more suggestive of ulcerative colitis. We examined whether preoperative serologic responses to these antigens were associated with Crohn's disease in indeterminate colitis patients after ileal pouch-anal anastomosis. METHODS: Twenty-eight indeterminate colitis patients undergoing ileal pouch-anal anastomosis were prospectively assessed for the development of pouchitis or Crohn's disease. Serologic responses were determined by enzyme-linked immunosorbent assay and immunofluorescence. Patients were classified based on four predominant profiles of antibody expression. Antibody profiles were determined before knowledge of clinical outcome. RESULTS: Median follow-up was 38 (range, 3-75) months. Of 16 patients (61 percent) who developed pouch inflammation, 4 (25 percent) had acute pouchitis and 12 (75 percent) had continuous pouch inflammation (9 had chronic pouchitis, 3 had Crohn's disease). No preoperative clinical factor predicted the development of these pouch complications. Overall, 16 patients (57 percent) had a positive antibody reactivity profile. Serologic expression of any marker alone did not predict the development of continuous pouch inflammation. However, continuous pouch inflammation developed in 10 of 16 patients (63 percent) who had a positive antibody reactivity profile compared with only 2 of 12 patients (17 percent) who had a negative antibody reactivity profile (P = 0.015). CONCLUSIONS: Indeterminate colitis patients who have a positive antibody reactivity profile before ileal pouch-anal anastomosis have a significantly higher incidence of continuous pouch inflammation after surgery than those with a negative profile.

Adolescent↗

Ileitis in ulcerative colitis: is it a backwash?

PURPOSE: This study aims to determine the incidence, demography, pathologic nature, and clinical significance of ileitis in ulcerative colitis patients who underwent restorative proctocolectomy. METHODS: A prospectively collected pouch database and the case notes of 100 consecutive patients who underwent restorative proctocolectomy for ulcerative colitis, under the care of a single surgeon, between 1988 and 2003 were reviewed. The original proctocolectomy specimens and pouch biopsies were reexamined and regraded blind, using the current diagnostic criteria. Patients were divided into two groups, those who had ileitis and those who had not. The demographic, clinical, and pathologic characteristics and the incidence of pouchitis of both groups were compared. RESULTS: Twenty-two patients had ileitis (22 percent). Compared with those with noninflamed ileum, patients with ileitis had a significantly shorter disease duration (P < 0.005), many of them presented or progressed to a fulminant state requiring acute surgical intervention (P < 0.01), had strong association with pancolitis and primary sclerosing cholangitis (P < 0.001), and had a higher incidence of subsequent development of pouchitis (P < 0.001). There was no correlation between the presence of ileitis and colitis severity. CONCLUSIONS: Ileitis in ulcerative colitis is not rare and does influence the prognosis, and the term "backw ash" is a misnomer. Ulcerative colitis with ileitis represents a distinct disease-specific subset of patients. Its true incidence and clinical significance can be determined only if detailed microscopic characterization of the terminal ileum is performed routinely in every patient with ulcerative colitis and the clinical outcome of these patients is audited prospectively.

Adolescent↗

Effects of exopolysaccharide-producing probiotic strains on experimental colitis in rats.

PURPOSE: Inflammatory bowel disease is suggested to result from a dysregulated immune response toward intestinal microflora, which may be restored by probiotic therapy based on the concept of healthy microflora. Ideal probiotic bacteria may be beneficial in inflammatory bowel disease; however, the mechanism of action and the clinical efficacy of probiotic usage are still unclear. In the present study, the effect of exopolysaccharide producing probiotics was evaluated on an experimental colitis model in rats. METHODS: Colitis was induced by intracolonic administration of acetic acid. Then, rats were treated daily with two probiotic strains, Lactobacillus delbrueckii subsp. bulgaricus B3 strain (exopolysaccharide of 211 mg/l: high-EPS group) or Lactobacillus delbrueckii subsp. bulgaricus A13 strain (EPS of 27 mg/l: low-EPS group), which were given into the stomach. The non-colitis-fed control group was only treated with high-exopolysaccharide strain. The model-control and control groups were treated only with tap water. Rats were killed after a seven-day treatment period. Disease activity was quantified by use of histologic scores and colonic myeloperoxidase activity, which is a marker of neutrophil infiltration during inflammation. RESULTS: The enhanced inflammatory response was accompanied by a higher level of myeloperoxidase activity in the colitis group. Histologic scores of colonic damage and myeloperoxidase activity were lower in both probiotic-treated groups compared with those of the colitis control group (P<0.001), although the mentioned scores improved significantly more in the high-EPS group than in the low-EPS group (P<0.001). CONCLUSIONS: Exopolysaccharide-producing probiotics significantly attenuate experimental colitis, which may be mediated by exopolysaccharide in a dose-dependent manner. Therefore, exopolysaccharide-producing probiotics may be a promising therapeutic role in inflammatory bowel disease.

Acetic Acid↗

Crohn's colitis: the incidence of dysplasia and adenocarcinoma in surgical patients.

PURPOSE: Data supporting an increased risk of colorectal cancer in patients with Crohn's colitis are inconsistent. Despite this, clinical recommendations regarding colonoscopic screening and surveillance for patients with Crohn's colitis are extrapolated from chronic ulcerative colitis protocols. The primary aim of our study was to determine the incidence of dysplasia and carcinoma in pathology specimens of patients undergoing segmental or total colectomy for Crohn's disease of the large bowel. In addition, we sought to identify risk factors associated with the development of dysplasia and carcinoma. METHODS: We performed a retrospective review of all patients operated on at our institution for Crohn's colitis between January 1992 and May 2004. Data were retrieved from patient charts, operative notes, and pathology reports. Logistic regression was used to model the probability of having dysplasia or adenocarcinoma. RESULTS: Two hundred twenty-two patients (138 females) who underwent surgical resection for the treatment of Crohn's colitis were included in the study. Mean age at surgery was 41 (range, 15-82) years and the mean duration of disease was 10 (range, 0-53) years. There were five cases of dysplasia (2.3 percent) and six cases of adenocarcinoma (2.7 percent). Three patients with dysplasia and one with adenocarcinoma were diagnosed on preoperative colonoscopy; while the other cases were discovered incidentally on pathologic examination of resected specimens. Factors associated with the presence of dysplasia or adenocarcinoma included older age at diagnosis (38.2 vs. 30.3 years, P = 0.02), longer disease duration (16.0 vs. 10.1 years, P = 0.05), and disease extent (90 percent extensive vs. 59 percent limited, P = 0.05). CONCLUSIONS: Patients with severe Crohn's colitis requiring surgery are at significant risk for developing dysplasia and adenocarcinoma, particularly when diagnosed at an older age, after longer disease duration, and with more extensive colon involvement.

Adenocarcinoma↗

Protective effect of comaruman, a pectin of cinquefoil Comarum palustre L., on acetic acid-induced colitis in mice.

The efficacy of comaruman CP, a pectin of marsh cinquefoil Comarum palustre L., was investigated using a model of acetic acid-induced colitis in mice. Mice were administered comaruman CP orally 2 days prior to rectal injection of 5% acetic acid and examined for colonic damage 24 hr later. Colonic inflammation was characterized by macroscopical injury, higher levels of myeloperoxidase activity, enhanced vascular permeability, and diminution of colonic mucus. Oral administration of comaruman CP was found to prevent progression of colitis. Colonic macroscopic scores and the total square of damage were significantly reduced in mice treated with CP compared with the vehicle-treated colitis group. Peroral pretreatment of mice with comaruman CP was shown to decrease tissue myeloperoxidase activity in colons compared with the colitis group. Comaruman CP was found to stimulate production of mucus by colons of normal and colitis mice. Comaruman CP decreased the inflammatory status of normal mice as elicited by reduction of vascular permeability and adhesion of peritoneal neutrophils and macrophages. Thus, a preventive effect of comaruman on acetic acid-induced colitis in mice was detected. Reduction of neutrophil infiltration and enhancement of colon-bound mucus may be implicated in the protective effect of comaruman.

Acetic Acid↗

Effect of colitis and ileoanal pouch on biliary enrichment of ursodeoxycholic acid in primary sclerosing cholangitis.

In primary sclerosing cholangitis (PSC), biliary enrichment of ursodeoxycholic acid (UDCA) may represent the decisive factor for its presumable beneficial effect. Up to now it is not clear how colitis and colectomy with ileo-anal pouch affect the biliary enrichment of UDCA and the biliary bile acid composition. We determined the biliary bile acid composition in 63 patients with PSC including 7 patients with ileo-anal pouch, 31 patients with colitis, and 25 patients without colitis. No differences existed between patients with and those without colitis. In patients with colectomy and pouch at a UDCA dose of 17.7 +/- 1.6 mg/kg (n = 7), biliary UDCA represented 46.4 +/- 6.7% (mean +/- SD) of total bile acids. An increase in the dose in six pouch patients from 12.5 +/- 0.9 to 22.3 +/- 1.6 mg/kg led to a slight increase in biliary enrichment of UDCA, from 39.8 +/- 8.1 to 49.4 +/- 10.7%. In five of seven patients with ileo-anal pouch, biliary UDCA enrichment was within the normal range, and in two of seven it was permanently or intermittently abnormally low. During UDCA treatment, in pouch patients the biliary content of deoxycholic acid and lithocholic acid was reduced, whereas all other bile acids were unchanged. In a minority of patients with ileo-anal pouch, biliary enrichment of UDCA may be markedly reduced, whereas patients with colitis have a biliary UDCA enrichment not different from that of patient without colitis.

Adult↗

Treatment of Clostridium difficile colitis and diarrhea with vancomycin.

Toxigenic Clostridium difficle is the major cause of antibiotic-associated colitis and is susceptible to vancomycin at fecal concentrations achieved with oral therapy. The effect of oral vancomycin was studied in 16 patients with C. difficile-related diarrhea or colitis, 12 of whom had colitis documented by endoscopy, biopsy, and/or barium enema. Four patients had antibiotic-associated diarrhea and possibly antibiotic-associated colitis, because sigmoidoscopy either showed normal results (two patients) or was not performed (two patients). Nineteen episodes of diarrhea were treated with oral vancomycin in two dosage regimens for three to 14 days. Twelve patients received 2 g daily, and four patients initially received 1 g or less per day. Within 48 hours of the start of vancomycin therapy, 14 of 16 patients (87 percent) showed a decrease in temperature, abdominal pain and diarrhea. Diarrhea ceased completely within two days of the start of vancomycin in nine episodes, within three to seven days in six episodes, and within eight to 14 days in the remaining four episodes, and within eight to 14 days in the remaining four episodes. Diarrhea recurred in two of these patients (12 percent) when the drug inciting the initial episode of colitis was given again 42 days or more after vancomycin therapy was stopped; both patients responded again to retreatment with vancomycin. Oral vancomycin is an effective treatment of C. difficile-related colitis and diarrhea.

Adolescent↗

An orally active non-selective endothelin receptor antagonist, bosentan, markedly reduces injury in a rat model of colitis.

Activation of endothelial cells by vasoactive mediators, such as endothelins, may be an early, strategically important step in the initiation of inflammation in the intestine. In view of recent evidence that inflammatory bowel disease is associated with elevated intestinal concentrations of endothelins and upregulated expression of endothelin receptors on vascular endothelium in intestine, endothelins may become therapeutic targets in inflammatory bowel disease. The recent availability of an orally active, mixed endothelin receptor antagonist, bosentan, allowed us to examine the role of endothelins in a rat model of colitis. Colitis was induced by intra-rectal administration of trinitrobenzene sulphonic acid. In each treatment group, rats were treated with bosentan (10-60 mg/kg p.o.) 24 and 2 h prior to (pre-dose) or 1 h after the induction (post-induction) of colitis and all animals were treated every 24 h thereafter for 5 days. On day 6, stool consistency and the presence of adhesions in the peritoneal cavity were accessed. Colonic tissue samples were removed for determination of macroscopic and microscopic tissue injury, and myeloperoxidase activity. Colitis was typified by tissue ulceration in the distal colon and a corresponding 35-fold increase in myeloperoxidase activity compared to non-inflamed controls. Daily treatment with bosentan dose-dependently reduced colonic damage and myeloperoxidase activity when bosentan was given prior to induction of colitis. In the pre-dose group, the greatest beneficial effect of bosentan was observed at 60 mg/kg; colonic damage and granulocyte infiltration were attenuated by > 80%. A partial therapeutic effect of bosentan was also observed at 60 mg/kg when the pre-treatment regimen was excluded. These findings demonstrate that an orally active, mixed endothelin receptor antagonist has marked protective and therapeutic effects in an animal model of colitis.

Administration, Oral↗