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PubMed1996

Protection by recombinant human interleukin-11 against experimental TNB-induced colitis in rats.

The potential effect of recombinant human interleukin-11 (rhIL-11) on trinitrobenzene sulfonic acid (TNB)-induced colitis was investigated in rats. Intrarectal TNB (40 mg in 0.25 ml 40% ethanol) produced significant ulcerative colitis. The lesions were most severe at three days after TNB instillation, and then declined, but lesions were still observed after two weeks. TNB administration also significantly enhanced the colonic mucosal myeloperoxidase (MPO) levels, which paralleled the severity of colitis. The rhIL-11 at subcutaneous doses of 300 or 1000 micrograms/kg daily for seven days, or 1000 micrograms/kg for three days when given after TNB significantly decreased lesion formation in TNB-induced colitis. These treatments also significantly reduced colonic mucosal MPO levels. TNB enhanced colonic mucosal levels of PGE2, LTB4, and TxB2, but these arachidonic acid derivatives were not affected by the present rhIL-11 treatments. TNB administration for three days caused a body weight loss that returned to normal after 14 days. The rhIL-11 significantly reduced colonic lesion severity and reduced colonic fecal blood loss. Given alone, rhIL-11 did not influence body weight. It can be concluded that rhIL-11 was protective against TNB-induced colitis and reactions of colonic MPO, but that these responses were not mediated through modulation of eicosanoid metabolism.

Animals↗
PubMed1995

Cyclosporine for the treatment of fulminant ulcerative colitis in children. Immediate response, long-term results, and impact on surgery.

PURPOSE: Emergency surgery for fulminant colitis is often complicated by high-dose steroid therapy, poor nutrition, and psychologic maladjustment. Cyclosporine is effective for fulminant ulcerative colitis in adults, resulting in avoidance of immediate surgery in 75 percent of patients and a 55 percent long-term remission rate. Over the last five years, we studied the effectiveness of cyclosporine in children with fulminant colitis. METHODS: Fourteen patients with ulcerative colitis (age, 7-20 years) received cyclosporine after satisfying the following criteria: 1) greater than five bloody diarrheal stools per day; 2) severe abdominal pain; 3) no improvement after ten days of bowel rest, 4) intravenous methylprednisolone (1-2 mg/kg/day); and 5) parenteral nutrition. Treatment was begun with oral cyclosporine (4.6-9.6 mg/kg/day), and the dose was adjusted to achieve whole blood trough levels measured with a monoclonal radioimmunoassay between 150 and 300 ng/ml. If improved, patients were discharged on oral cyclosporine, prednisone, and a regular diet. RESULTS: Eleven of 14 patients (78 percent) responded within two to nine days and were able to consume a normal diet, had three or less soft stools per day, and had no pain. One did not respond after ten days and underwent an ileal pouch-anal anastomosis procedure. Two patients elected surgery after 20 days of therapy and a partial response. Of 11 patients who left the hospital, 4 had recurrent symptoms after 2 to 11 months of taking therapeutic doses of cyclosporine and 3 flare ups while weaning from cyclosporine after 4 to 8 months. Three patients have been weaned from cyclosporine after 8 to 13 months and have remained in remission from six months to five years. One patient is about to complete a six-month course of cyclosporine. Overall ten (72 percent) have undergone surgery, including 7 of 11 who responded initially to cyclosporine and left the hospital. Weight (P < 0.001), albumin (P < 0.01), erythrocyte sedimentation rate (P > 0.05), and prednisone dose (P < 0.001) improved significantly in the seven patients on cyclosporine who responded initially, left the hospital, and subsequently underwent surgery. CONCLUSIONS: Cyclosporine is effective in achieving clinical remission in 80 percent of children with refractory fulminant colitis; however, within one year, most initial responders will require colectomy because of a flare up of the disease. In a majority of patients, the role of cyclosporine therapy is to rapidly ameliorate symptoms and prevent precipitous colectomy, improve nutrition and psychologic adaptation, and reduce the steroid dose leading to surgery in a well-prepared patient.

Abdominal Pain↗
PubMed1995

Lack of crucial role of mast cells in pathogenesis of experimental colitis in mice.

Mast cell alterations have been implicated in the pathogenesis of chronic ulcerative colitis (UC). We studied the effect of mast cell deficiency of the severity of inflammation in a murine model of colitis. Colitis was induced in mice using dextran sodium sulfate (DSS). Mast-cell-deficient mice (WBB6F1/J-W/WV; N = 17) and normal littermates (WBB6F1/J-+/+; N = 17) were administered DSS 4% w/v for seven days, then water alone for one week, followed by 5% DSS for six days. Animals were sacrificed at the end of the protocol. Segments of proximal, mid-, and distal colon of each animal were processed for histopathological examination. Mortality and morbidity (diarrhea and weight loss) for each group were assessed. There was no significant difference between the two groups in either their clinical parameters (mortality and morbidity) or the severity of colitis as graded histopathologically. Our findings suggest that mast cells are not crucial for the development of DSS-induced colitis.

Animals↗
PubMed1999

Crohn's disease-associated genetic marker is seen in medically unresponsive ulcerative colitis patients and may be associated with pouch-specific complications.

PURPOSE: Genetic markers have been used to define subgroups of patients within the broad categories of Crohn's disease and ulcerative colitis that may differ in clinical course and response to medical therapy. The tumor necrosis factor microsatellite haplotype a2blc2d4e1 has been found previously to be present in 24 percent of patients with Crohn's disease and only 5 percent of patients with ulcerative colitis. This study examined associations between this microsatellite haplotype and the postoperative clinical course of patients with ulcerative colitis undergoing ileal pouch-anal anastomosis. METHODS: As part of a large, controlled, prospective study to correlate genetic markers with clinical phenotypes, tumor necrosis factor microsatellite alleles at five loci (a, b, c, d, and e) were determined from genomic DNA by polymerase chain reaction in 32 patients with a clinical and histopathologic diagnosis of ulcerative colitis who underwent ileal pouch-anal anastomosis for medically unresponsive disease. All patients with ileal pouch-anal anastomosis were also studied prospectively for pouch-specific complications. RESULTS: The tumor necrosis factor haplotype a2blc2d4e1 was present in 11 patients. Median follow-up was 19 months. Thirteen patients had a pouch-specific complication (12 pouchitis and 1 pouch-perineal fistula). Six of 11 patients (55 percent) with the haplotype had a pouch-specific complication compared with 7 of the 21 patients (33 percent) who did not possess this haplotype (P = 0.22). Median time from surgery to pouch-specific complication was eight months. Patients with the haplotype had a median time to pouch-specific complication of three months, whereas patients without the haplotype had a median time of 11 months (P = 0.04). In addition, 36 percent of patients with the haplotype had chronic pouch complications vs. only 10 percent of patients without the haplotype (P = 0.05). CONCLUSION: The Crohn's disease-associated tumor necrosis factor haplotype a2blc2d4e1 may define a subgroup of medically unresponsive patients with ulcerative colitis who are predisposed to a higher incidence of pouch-specific complications after ileal pouch-anal anastomosis.

Adult↗
PubMed2001

Portal vein thrombosis successfully treated with a colectomy in active ulcerative colitis: report of a case.

Portal vein thrombosis is a rare complication in ulcerative colitis. We present a patient with portal vein thrombosis in ulcerative colitis who was successfully treated with colectomy. A 38-year-old Japanese female was admitted to our hospital because of an exacerbation of colitis. Abdominal ultrasonography performed because of liver dysfunction showed the thrombus in an umbilical portion of the portal vein. The patient underwent a subtotal colectomy and ileostomy because her colitis did not respond to intensive intravenous therapy. Although portal vein thrombus was treated with an intravenous infusion of urokinase before the operation, no change in the thrombus size was found. Approximately three months after the colectomy, the thrombus of the portal vein disappeared without anticoagulant therapy. Although a resection of an inflamed colon may be theoretically effective in the thrombosis in the inflammatory bowel disease, its benefit has not been confirmed. Our case suggests that the resection of the diseased bowel may have a favorable effect on the course of portal vein thrombosis in acute attacks of ulcerative colitis.

Adult↗
PubMed1999

Functional outcome of conversion of ileorectal anastomosis to ileal pouch-anal anastomosis in patients with familial adenomatous polyposis and ulcerative colitis.

PURPOSE: The aim of this study was to review the functional outcome in 20 patients with familial adenomatous polyposis and ulcerative colitis who were converted from ileorectal anastomosis to ileal pouch-anal anastomosis. METHODS: From 1985 to 1997, 12 patients with familial adenomatous polyposis (5 males; mean age, 39.1 years) and 8 patients with ulcerative colitis (5 males; mean age, 36.7 years) underwent conversion from ileorectal anastomosis to ileal pouch-anal anastomosis. Clinical and operative data were analyzed retrospectively. Functional results were obtained by telephone interview in 16 patients (94 percent) after pouch construction. Four patients were not interviewed (2 were deceased, 1 was lost to follow-up, and 1 was not reachable). RESULTS: Indications for conversion were uncontrollable rectal polyps (10 patients) and colonic cancer found in the pathology specimen after ileorectal anastomosis in patients with familial adenomatous polyposis (2 patients), intractable proctitis (5 patients), colonic cancer found in the pathology specimen of patients with ulcerative colitis after ileorectal anastomosis (2 patients), and rectal dysplasia (1 patients). Mean follow-up time was 5 (range, 1-11) years. Ileal pouch-anal anastomosis was handsewn in 14 patients, and the remaining cases were double-stapled in 4 patients with ulcerative colitis. No intraoperative difficulties were reported in 13 cases; technical problems were related to adhesions (3 cases), difficult rectal dissection (2 cases), and stapler-related difficulties (2 cases). Postoperative complications after ileal pouch-anal anastomosis included small-bowel obstruction (4 patients) and ileal pouch-anal anastomosis leak (1 patient). Patients with ileorectal anastomosis vs. those with ileal pouch-anal anastomosis had a better functional outcome with regard to nighttime continence (14 (88 percent) vs. 6 (38 percent) patients) and average bowel movements (<6/day; 12 (75 percent) vs. 4 (25 percent) patients). Complete daytime continence, 15 (94 percent) vs. 10 (62 percent) patients, was similar in the two groups. Physical and emotional well-being were similarly rated as very good to excellent. CONCLUSIONS: In patients with familial adenomatous polyposis and ulcerative colitis with ileorectal anastomosis, conversion to ileal pouch-anal anastomosis may be required. In view of the risk of rectal cancer or intractable proctitis, patients seem to accept the conversion in spite of poorer bowel function.

Adenomatous Polyposis Coli↗
PubMed1977

Radiology in the current assessment of ulcerative colitis.

Plain abdominal radiography in acute ulcerative colitis is essential to detect acute colonic complications, such as acute dilatation and free perforation. Sealed perforations may not be detected. Useful information can be gained as to the extent and severity of the mucosal lesions, but can be unreliable so that a contrast examination is required. The double contrast barium enema is more accurate than the single contrast study in revealing the early mucosal lesions of colitis. It is the examination of choice to show the extent and severity of disease, and is of considerable value in the differential diagnosis of colitis. In active colitis, the unprepared double contrast barium enema is recommended. The success of the examination relies on the absence of fecal residue adjacent to an active mucosa. The technique, uses, and limitations of this type of examination are described. In the long-term management of colitis, the role of radiology is to show the presence of extensive disease, which indicates an increased risk of malignancy. Lesions such as strictures or polyps may be found and are more likely to be benign than malignant, but confirmation often requires endoscopic biopsy. In the search for malignancy regular barium enema examination is not recommended, as this can only reveal an overt tumor, whereas premalignancy can be detected histologically from an endoscopic biopsy.

Colitis, Ulcerative↗
PubMed1986

Long term follow-up of surgical treatment for ulcerative colitis--with special reference to recurrence and the quality of life.

From 1961 to 1984, fifty-one patients with ulcerative colitis were surgically treated at Tohoku University Hospital. The results of various types of surgical treatments for ulcerative colitis were analysed and discussed with special reference to recurrence and the quality of life at the time of follow-up. Total colitis and left-sided colitis were observed in 42 and 9 patients, respectively. There were five operative deaths. Thirteen patients received total proctocolectomy and 38 patients received various types of conservative operations at the first operation. In seven patients there was a recurrence of the disease in the retained colon or rectum and proctocolectomy with ileostomy was carried out. Forty-six patients were followed. Four died of other diseases and two were lost to follow-up. The periods of follow-up after the final operation ranged from 3-29 years. The types of operative procedures were ileostomy in 19, ascendicostomy in 14, ileoproctostomy in 6 and ascendicoproctostomy in 1 patient. Following treatment of recurrence of the disease, in most patients who had undergone various surgical treatments, favorable results of quality of life were attained, even in those with ileostomy. These results indicate that it is important to select the most proper types of operative procedures for surgical treatment of ulcerative colitis by individualizing each case.

Adolescent↗
PubMed1985

Colorectal cancer in familial polyposis coli and ulcerative colitis.

The records of all patients with familial polyposis coli and ulcerative colitis operated at The Mount Sinai Hospital were reviewed to determine the proportion of patients with cancer at the time of colon resection. Sixty-nine patients with familial polyposis coli undergoing operation between 1947 and 1983 were identified and 25 (36 percent) were found to have cancer. In the group with ulcerative colitis, 548 patients had surgical treatment between 1957 and 1983 and 65 (12 percent) had colonic cancer. There was a significant decrease in the proportion of patients with familial polyposis coli having cancer at the time of colon resection from 50 percent before 1968 to 20 percent since 1978. This change in cancer incidence was found to correlate with a decrease in the mean age at operation from 40 to 25 years. In the group with ulcerative colitis, the mean age at operation has remained essentially unchanged at 36 years. The proportion of patients with ulcerative colitis having cancer at the time of colon resection has remained constant throughout this study. Progression to carcinoma is still a significant concern in both familial polyposis coli and ulcerative colitis. Although removal of the colon and rectum prevents cancer development, patient selection and timing of the operation remain a difficult problem.

Adolescent↗
PubMed1986

Ischemic colitis and immunosuppression. An experimental model.

The incidence of ischemic colitis in renal transplant recipients approaches 1 percent. The mortality in these patients with ischemic colitis is nearly 70 percent. Immunosuppressive agents have been implicated in the development of ischemic colitis. To study the effect of immunosuppressive agents on ischemic colitis, a 4-cm segment of the colon was devascularized in 27 male Fischer rats. The animals were divided into one control and two treatment groups. One treatment group received methylprednisolone and the other, azathioprine, in doses similar to those of renal transplant recipients. Both experimental groups, either separately or combined, showed significantly greater areas of colonic ischemic changes than did the control group. This study demonstrates that systemic administration of immunosuppressive agents may augment the development of ischemic colitis.

Animals↗
PubMed1989

Outcome of "indeterminant" colitis following ileal pouch-anal anastomosis.

To establish whether patients with indeterminant colitis (patients with ulcerative colitis whose surgical specimens also show features of Crohn's colitis) have an adverse outcome after ileal pouch-anal anastomosis (IPAA), the authors reviewed the pathologic reports and postoperative status of 514 consecutive patients who underwent IPAA for chronic ulcerative colitis (CUC). Twenty-five patients (5 percent) had features of indeterminant colitis (IC), including unusual distribution of inflammation, deep linear ulcers, neural proliferation, transmural inflammation, fissures, creeping fat, and retention of goblet-cell population. The clinical and functional outcome of these 25 IC patients was compared with that of the remaining 489 CUC patients. The mean follow-up was 38 +/- 18 months. No significant differences in complication rates, pouch function, incidence of "pouchitis," or requirement for pouch excision were detected in the two groups at follow-up. Although the authors are continuing to perform IPAA on patients with IC, a better definition of the IC patient and a more objective, prospective analysis of outcome of IC following IPAA is required before confident and specific treatment policies can be recommended.

Adult↗
PubMed1988

Mucin abnormality of colonic mucosa in ulcerative colitis associated with carcinoma and/or dysplasia.

Twenty cases of resected specimens of carcinoma and/or dysplasia complicating ulcerative colitis were histochemically investigated by the periodic acid-thionein Schiff/potassium hydroxide/periodic acid-Schiff (PAT/KOH/PAS) staining method to see mucin characteristics of carcinoma, dysplasia, and the background mucosa of these lesions. As a control, 11 resected specimens of ulcerative colitis without dysplastic changes and 26 specimens of colonic carcinoma were examined also. All dysplasia and carcinoma in ulcerative colitis stained blue, whereas normal colonic mucin stained red in 65 percent. In 14 of 20 specimens with carcinoma and/or dysplasia, the background mucosa appeared normal with hematoxylin and eosin staining, but showed a mosaic staining pattern with PAT/KOH/PAS. However, only two of 11 specimens of ulcerative colitis without dysplasia and none of 26 specimens of flat mucosa with colorectal carcinoma showed a mosaic staining pattern. From these observations it was concluded that the PAT/KOH/PAS staining method could be useful as a histochemical marker of premalignant change in longstanding ulcerative colitis.

Colitis, Ulcerative↗
PubMed1977

Spontaneous ischemic colitis.

Eighteen cases of spontaneous ischemic colitis are reviewed. The diagnosis was established according to the following criteria: 1) clinical background, 2) clinical characteristics, 3) morphologic characteristics, and 4) clinical and morphologic course. The last three constituted the diagnostic criteria. The cases were divided into mild-to-moderate, moderate-to-severe, and gangrenous categories. Although data on clinical background did not establish the diagnosis of spontaneous ischemic colitis, they were essential in strict diagnosis. Patients who had histories of Crohn's disease, chronic ulcerative colitis, and recent antibiotic administration were excluded from consideration. Appropriate stool examinations obtained in all of the mild-to-moderate and all except two of the moderate-to-severe cases excluded colitis due to pathogenic bacterial organisms or parasites. Spontaneous ischemic colitis generally occurs in older individuals; the average age in our patients was 60 years. Twelve of the 18 patients had at least some evidence of major cardiovascular disease.

Adult↗
PubMed1981

Evanescent colitis.

Evanescent colitis was first reported in 1971. This clinical entity is manifested by abrupt onset of colicky abdominal pain usually out of proportion to the physical findings, loose stools progressing to hematochezia, and segmental colonic involvement with spontaneous resolution in a matter of days. The diagnosis can be suggested by abdominal flat plate; confirmation depends upon barium-enema examination early in the course of the illness. The clinical presentation is identical to that of colonic ischemia with one remarkable exception: while colonic ischemia has come to be regarded as a disease of the elderly, usually with underlying vascular disease, evanescent colitis occurs in young people who are otherwise free of disease. In this report the authors present nine cases whose course is classic for colonic ischemia except that they are all less than 50 years of age and free of underlying vascular disease. Two of the patients were on oral contraceptive medication. A review of the literature revealed 15 additional cases. Five of these cases were associated with oral contraceptives. Conditions to be excluded in the differential diagnosis of this disease are the specific infectious colitides, idiopathic ulcerative colitis, granulomatous colitis and antibiotic-related pseudomembranous colitis.

Acute Disease↗
PubMed1978

Studies on the subpopulation and function of peripheral lymphocytes, and lymphocyte reactivity to colonic mucosal antigen and bacterial antigen in patients with ulcerative colitis and Crohn's disease.

Immunological studies were carried out in fifteen cases of ulcerative colitis, three cases of tuberculous colitis, four cases of Crohn's disease and one case of Behcet's disease diagnosed by X-ray, endoscopy or biopsy mainly from the standpoint of cellular immunity. In patients with ulcerative colitis the T-cell population and PHA responsiveness of peripheral lymphocytes were both depressed more than in the control group. At different stages of the disease, the deviation of the values of PHA responsiveness of lymphocytes showed a rather wide range in the active stage and there was also immunological instability. However, when the disease entered remission, the immunological conditions settled down and the pathological condition appeared stable. In contrast to the nonspecific immunological conditions mentioned above, characteristically, there were many examples of a positive lymphocyte response to colonic mucosal and bacterial antigens. In all cases of Crohn's disease the lesions are in the small intestine and there was a reduced response to PHA lymphocytic stimulation which was more pronounced than that in patients with ulcerative colitis. PHA response was also high in tuberculous colitis cases.

Adult↗
PubMed2002

Antibodies against hepatoma-derived growth factor and mucosal repair in ulcerative colitis.

Ulcerative colitis is a chronic inflammatory disease of colonic mucosa in which the pathogenesis of any immunological disorders would likely be related. Various circulating autoantibodies have been reported in patients with ulcerative colitis, although their possible roles in this disease process have not yet been clarified. Autoantibody against hepatoma-derived growth factor (HDGF) was detected at high frequency in the serum of patients with ulcerative colitis, especially in patients with total colitis and left-sided colitis. In pursuit of the possible role of anti-HDGF autoantibody in the pathogenesis, we investigated HDGF expression in the intestinal mucosa by Western blotting and immunohistochemistry and the effects of recombinant proteins and antirecombinant HDGF antibody on the proliferation of the colonic epithelial cell-derived cell line, HT-29. HDGF was expressed in the nucleus of the colonic epithelial cells dominantly in the bottom of the crypts. Recombinant HDGF stimulated the proliferation of HT-29 cells significantly, although its effects were small, about 20% greater than the control at 100 ng/ml. On the other hand, the polyclonal IgG antibody against recombinant HDGF generated by rabbits suppressed their proliferation almost completely at 250 microg/ml. These findings suggest that HDGF plays an important role in epithelial cell renewal of intestinal crypts as a growth and survival factor, and that autoantibody against HDGF may delay mucosal healing and repair by inhibiting the stimulatory effects of HDGF on epithelial cell proliferation, resulting in a chronic process of colonic mucosal injury.

Autoantibodies↗
PubMed2002

Antigen-presenting dendritic cells in ulcerative colitis.

BACKGROUND: Antigen-presenting dendritic cells are the inducers and regulators of immune responses. Here, we have discussed the phenotype and function of dendritic cells in situ and their alteration during lymphocytapheresis in patients with ulcerative colitis. METHODS: Dendritic cells were enriched from the peripheral blood mononuclear cells by culturing with granulocyte-macrophage colony-stimulating factors and interleukin 4 for 8 days. The function of dendritic cells was evaluated in an allogenic mixed leukocyte reaction. Flow cytometry was employed to study the phenotype of dendritic cells. Lymphocytapheresis was done by a continuous flow centrifugation technique using a CS-3000 separator. Immunohistochemical methodology was employed to detect dendritic cells at the colonic mucosa. RESULTS: Peripheral blood dendritic cells had increased functional capacity, and these cells were matured and activated compared to dendritic cells from normal controls. CD83-positive activated and mature dendritic cells were found at the colonic mucosa from patients with ulcerative colitis. Lymphocytapheresis induced decreased function of peripheral blood dendritic cells in patients with ulcerative colitis. Also, the levels of inflammatory cytokines were reduced by lymphocytapheresis. CONCLUSIONS: Increased function of dendritic cells may be related to the inflammatory mucosal milieu found in patients with ulcerative colitis. Depletion of dendritic cells during lymphocytapheresis may downregulate the exacerbated immune response in patients with ulcerative colitis.

Antigen-Presenting Cells↗
PubMed2000

Circulating autoantibodies against purified colonic mucin in ulcerative colitis.

To clarify the role of colonic mucin in the autoimmune process of ulcerative colitis, circulating antibodies against human colonic mucin were investigated. Purified colonic mucin, obtained from human colonic mucosa by gel filtration, using a Bio-Gel A-1.5-m column and CsCl equilibrium density gradient, was divided into soluble mucin (S-mucin) secreted extracellularly and membranous mucin (M-mucin) binding to cell membrane. Sodium dodecylsulfate polyacrylamide gel electrophoresis and Western blotting analysis showed that antibodies in the serum samples of some patients with ulcerative colitis recognized purified S- and M-mucin of >180-kD. By enzyme-linked immunosorbent assay (ELISA), anti-mucin antibodies were detected in 11 of 60 patients with ulcerative colitis (18%). In contrast, the antibodies were not detected in 22 patients with Crohn's disease. The titers of antimucin antibodies against S-mucin and M-mucin were not different in each patient. By ELISA using mucin in which the sugar chains were destroyed by neuraminidase or NaIO4 treatment, it was demonstrated that anti-mucin antibodies recognized the epitopes of either the sugar chain or the core protein exposed through destruction of the sugar chains. We then investigated the relationship between anti-mucin antibodies and the patients' clinical features. Anti-mucin antibodies were detected in 6 of 15 patients with chronic continuous type ulcerative colitis (40%) and in 5 of 26 patients with relapsing-remitting type (19%), but there was no antimucin antibody-positive serum in patients who had had only one attack without any relapse. These results suggest that anti-mucin antibodies could be a disease marker for ulcerative colitis and that immunological abnormalities in colonic mucin contribute to the persistence of colonic mucosal inflammation.

Autoantibodies↗