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PubMed1989

Alterations in serum immunoglobulin G subclasses in patients with ulcerative colitis and Crohn's disease.

We have examined the concentration of immunoglobulin G (IgG) subclass antibodies in the sera of 27 patients with ulcerative colitis and 21 patients with Crohn's disease as well as in 11 normal controls and 11 patients with systemic lupus erythematosus. In comparison with a control mean serum IgG1 concentration of 5173 micrograms/ml, patients with ulcerative colitis exhibited a significantly increased mean serum concentration of 7924 micrograms/ml (p less than 0.05), whereas patients with Crohn's disease had a near normal mean serum IgG1 level of 5898 micrograms/ml. In contrast, control sera had a mean IgG2 level of 2477 micrograms/ml and ulcerative colitis sera had a similar IgG2 level of 2269 micrograms/ml, whereas Crohn's disease sera had a significantly increased mean IgG2 level of 5111 micrograms/ml (p less than 0.05). Patients with systemic lupus erythematosus, like those with ulcerative colitis, had a markedly elevated serum IgG1 level of 15,594 micrograms/ml (p less than 0.001) without a significantly increased IgG2 serum level (3271 micrograms/ml). Neither ulcerative colitis nor Crohn's disease sera exhibited altered levels of IgG3 or IgG4. These data show that alterations in IgG subclass concentrations occur in the sera of patients with active, untreated inflammatory bowel disease, similar to the previously noted changes in the IgG subclasses secreted by lymphocytes from involved inflammatory bowel disease intestinal specimens.

Adult↗
PubMed1988

Differences in cellular glycoconjugates of quiescent, inflamed, and neoplastic colonic epithelium in colitis and cancer-prone tamarins.

In the preceding paper the authors demonstrated that the lectin staining patterns of normal colonic epithelium obtained from colitis and carcinoma-prone cotton top tamarins (CTTs), Saguinus oedipus, a New World primate, differs from colitis- and carcinoma-resistant primate species. In this study they determined the usefulness of cytochemical features in inflamed epithelium as indicators for malignant change. They compared the lectin staining pattern in inflamed mucosa and adjacent mucosa with colonic carcinoma from 8 CTTs with that of 9 clinically healthy CTTs with no histologic evidence of colitis. Deparaffinized sections were labeled with ten biotinylated lectins and stained by the avidin-biotin peroxidase complex method. Numerous significant differences were demonstrated in the lectin staining pattern between normal epithelium and colonic carcinoma; fewer between normal and chronic inflamed epithelium. However, between chronic inflamed epithelium and colonic carcinoma significant staining differences were observed with only two lectins, peanut agglutinin (PNA) and Ulex europaeus agglutinin-I (UEA-I). These findings suggest that there is a progression in alteration of lectin staining pattern from normal epithelium, via chronic colitis, to colonic carcinoma. Furthermore, the differences between chronic colitis and colonic carcinoma are expressed only with those lectins that are associated with malignant transformation of human colonic epithelium.

Animals↗
PubMed1988

Visceral surface oxygen tension in experimental colitis in the rabbit.

The impairment of bowel healing that is characteristic of inflammatory bowel disease (IBD) is poorly understood. Because bowel healing is related to the adequacy of perfusion in other circumstances, we studied bowel surface oxygen tension (PSO2), which is related to bowel perfusion, in rabbits with IBD. Both cell-mediated (n = 17) and immune complex-mediated (n = 10) colitis caused marked attenuation of colon PSO2. Control (n = 13) left colon PSO2 was 36 +/- 5 (SEM) torr. In mild colitis, left colon PSO2 fell to 11 +/- 5 torr, and in severe colitis it fell to 4 +/- 1 torr (p less than 0.01 for each compared with control). These changes occurred irrespective of the mechanism of induction of colitis. Gastric and small intestinal PSO2 were unaffected. Hepatic and renal PSO2 were decreased in severe colitis only. The presence of decreased PSO2 was a better marker for the presence of IBD than was histologic evaluation. It is suggested that attenuation of PSO2 may be a marker for the physiologic activity of IBD. If this is so, PSO2 may prove a useful adjunct in the operative management of IBD.

Animals↗
PubMed1978

Protective effect of metronidazole in experimental ulcerative colitis.

Administration of carrageenan to guinea pigs produces colonic lesions which are similar to those noted in idiopathic ulcerative colitis of human beings. This model was used to determine fecal flora changes and response to antimicrobial probes during the evolution of carrageenan-induced colitis. The results of fecal flora analysis showed that mean coliform concentrations increased from 10(2.7) to 10(7.4) per g during the initial stages of colonic ulceration. Pretreatment of carrageenan recipients with antimicrobials directed against coliforms reduced the concentrations of these organisms, but failed to attenuate the disease process. On the other hand, pretreatment with metronidazole, an antimicrobial primarily active against anaerobic bacteria, prevented carrageenan-induced colitis in a majority of animals. Delayed treatment with metronidazole until after colitis was established showed no salutory benefits. These results suggest that anaerobic bacteria play a role in the initial events of carrageenan-induced colitis in the guinea pig model.

Animals↗
PubMed1986

Ulcerative colitis in Stockholm County--a study of epidemiology, prognosis, mortality and cancer risk with special reference to a surveillance program.

The epidemiology of ulcerative colitis (UC) in Stockholm County 1955-79 was investigated. There were 1274 cases. The proportion of patients with proctitis, left-sided and total extent of disease remained constant over the study period. The incidence increased over the first 20 years followed by a plateau. The peak incidence in relation to age increased slightly but remained in the third and fourth decade through the study period. The incidence in men over 40 years of age increased markedly towards the end of the study. There were 109 deaths at follow-up (Dec. 1981) among those having the UC diagnosis between 1955-1979. Twentysix out of 41 patients who died due to UC did so postoperatively. The mortality pattern among those 68 patients who had causes of death unrelated to UC was similar to the expected. There was a decrease in cumulative survival probability compared with the expected, in particular in those with total colitis. This was also seen when only deaths unrelated to UC were included suggesting an increased sensitivity to the ordinary disease spectrum in UC patients. Between 1945-1979 there were 1339 patients who had UC diagnosed. Twentyfive of those had developed colon cancer (24 with total colitis) at follow-up (Dec. 1981). Eighteen were dead at follow-up, the survival time being in direct relation to the Dukes' grading at cancer diagnosis irrespective of age. The cumulative cancer risk at 25 years duration (total colitis patients only) was 13% (SD 4%) compared to the expected 1,9%. In a selected group of 71 patients followed for cancer surveillance during the period 1974-82 nine patients developed at least low grade dysplasia including one Dukes' A carcinoma. The dysplasia or cancer leading to operation was found above the rectum in four of five operated patients, all having total colitis with a duration ranging between 25-44 years.

Adolescent↗
PubMed1983

Increased colonic adenylate cyclase activity in active ulcerative colitis.

To investigate the pathogenesis of diarrhea in ulcerative colitis, colonic adenylate cyclase activity was determined in patients and normal subjects. Basal adenylate cyclase activity in 19 patients with active disease [61.5 +/- 9.6 (mean +/- SE) pmol cyclic adenosine monophosphate/mg protein . 10 min] was two times higher (p less than 0.01) than its activity in colonic mucosa of 30 normal subjects or 10 ulcerative colitis patients in remission [31.4 +/- 2.0 and 23.6 +/- 1.9 pmol cyclic adenosine monophosphate/mg protein . 10 min, respectively]. The enzyme activity was stimulated to the same extent in all groups by sodium fluoride, vasoactive intestinal polypeptide, or by substitution in the assay mixture of guanosine triphosphate by its hydrolysis-resistant analogue--GTP gamma S. Prostaglandin E2 significantly stimulated the enzyme activity in tissue obtained from normal subjects, patients with shigellosis, and ulcerative colitis patients in remission while it had no effect on adenylate cyclase activity in colonic mucosa of patients with active ulcerative colitis. These results suggest that stimulation of colonic adenylate cyclase activity, possibly secondary to the reported enhanced colonic prostanoid synthesis, may contribute to the diarrhea in ulcerative colitis.

Adenylyl Cyclases↗
PubMed1978

[Pathology of ulcerative colitis (author's transl)].

The macroscopic and histological appearance, and the local immune response in ulcerative colitis are discussed. The main criteria for the differentiation between ulcerative colitis and Crohn's disease of the large bowel are reviewed. The risk to develope carcinoma in the large bowel is greater in patients with total ulcerative colitis than in the general population. Precancerous changes in rectal and colonoscopical biopsies are a useful parameter in detecting early cancer in colitis. A description of the morphology of precancerous changes in ulcerative colitis is given.

Biopsy↗
PubMed1982

Abnormalities of T cells in patients with ulcerative colitis. FACS analysis of peripheral lymphocytes.

Heterologous antisera against human brain tissue and human embryonal thymocytes were used to distinguish the changes in lymphocyte subpopulations accompanying ulcerative colitis. Peripheral lymphocytes from normal individuals and from patients with ulcerative colitis were reacted with these heterologous antibodies, stained with fluoresceinated rabbit anti-human immunoglobulins, and analyzed by fluorescence-activated cell sorter. All of the fluorescence profiles of T cells in ulcerative colitis showed shifts with a marked increase in the population that had high fluorescence intensity. Time-course analysis by fluorescence-activated cell sorter revealed that the grade of fluorescence profile shift varied in accordance with the activity of the disease. Natural T-cell toxic autoantibody was found in 27 of the 35 patients with ulcerative colitis. Natural T-cell toxic autoantibodies from these patients reacted with 20% of peripheral T cells without Fc receptors. The abnormality of peripheral blood lymphocytes in ulcerative colitis may be caused by the production of autoantibodies.

Antigens, Surface↗
PubMed1983

Assessment of colorectal cancer risk in patients with ulcerative colitis: experience from a private practice.

The cumulative risk of developing colon cancer in patients with ulcerative colitis has been stated to increase 10%-20% for every decade of duration of disease after 10 yr. We reviewed the clinical course of 673 patients with inflammatory bowel disease restricted to the colon who were seen by the authors since 1955. A subset of 258 patients with a diagnosis of ulcerative colitis established before 1970 and followed by the authors was studied by both the classical life table and a generalized approach to estimate the risk of colorectal carcinoma. Only nine instances of colorectal carcinoma occurred. Using the former method and eliminating 3 patients referred with known colorectal carcinoma, the actuarial risk for developing this complication for all patients, regardless of extent of disease, was computed to be only 6.6% at 26 yr and 11.4% at 32 yr following the onset of ulcerative colitis. The cumulative probability of colorectal carcinoma among patients with universal colitis at 26 yr was 19.7% by the generalized method and 11.6% using the standard life table. The generalized approach consistently gave higher risk estimates due to a smaller number of patients in the denominator of the risk calculation. Using an alternative method, we calculated cancer risk from the date first seen for patients with universal extent and a history of greater than or equal to 10 yr of disease (means = 17.4 yr). The magnitude of the resulting colorectal carcinoma risk was even less than previously reported in hospitalized patients. This method is more suited for colorectal carcinoma risk assessment of a large series of ulcerative colitis patients seen in private practice and the results should modify the fear of cancer development in these patients.

Actuarial Analysis↗
PubMed1981

Pseudomembranous colitis in renal transplant recipients; plain film findings.

The plain abdominal film findings in nine renal transplant patients with pseudomembranous colitis were characteristic of but not specific for this entity and most commonly showed "thumb-printing" reflecting submucosal edema (five patients) and a persisting localized segmental ileus in the colon (five patients). Based on the plain film findings, the differential diagnosis will include the acute stages of ulcerative colitis, granulomatous colitis, ischemic colitis and other inflammatory colitides, but the radiologist is in a position to suggest the correct diagnosis in the appropriate clinical setting. A barium study of the colon is not indicated, as diagnosis is usually accomplished by endoscopy. The etiology of this colitis has recently been shown to be a cytopathic toxin of the anaerobic bacterium, Clostridium difficile.

Adult↗
PubMed1982

Surgical management of ulcerative colitis.

Most patients with universal ulcerative colitis ultimately require a colectomy either to treat the inflammatory process or to prevent the subsequent development of a malignant tumour. Since the introduction of total proctocolectomy and ileostomy for the definitive surgical management of ulcerative colitis, this procedure has become the standard operative therapy for this disease. The description of the eversion technique of ileostomy in 1952 improved the life-style of patients with an ileostomy and made the total proctocolectomy a more attractive procedure. Nevertheless, many patients are emotionally disturbed by having an incontinent ileostomy and often will delay their surgery because of the associated psychologic trauma. Because of this, the Kock pouch or continent ileostomy has been introduced and advocated during the past decade. This procedure has met with notable success but has found less application in the younger patient. However, even the continent ileostomy is associated with a certain amount of psychologic trauma because of the abdominal stoma. Therefore, the endorectal pull-through has recently been used for the management of ulcerative colitis. First introduced in 1948, this procedure allows total removal of the diseased bowel, maintains continence and eliminates the need for an ileostomy. During the last 3 1/2 years, the author has used the endorectal pull-through to treat 24 patients with ulcerative colitis and 1 with familial polyposis. The results are encouraging in that all patients are continent and the average daily stool frequency is 6 to 10. These results and those of others support the continued use of this new surgical approach to the management of ulcerative colitis.

Adolescent↗
PubMed1995

Low prevalence of anti-neutrophil cytoplasmic antibodies in ulcerative colitis patients with long-term remission.

OBJECTIVES: In spite of a strong positive association between ulcerative colitis and the presence of perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCAs), the immunogenetic significance of these antibodies remains unclear. We studied patients with quiescent disease to clarify whether ANCAs are present even in the absence of inflammation. DESIGN: The prevalence of ANCAs was estimated blindly in 137 patients with ulcerative colitis, 128 of whom had quiescent disease with a mean duration of complete clinical and biochemical remission of 14 years. For comparison, we studied sera from 110 patients with Crohn's disease, 27 of whom had a low or intermediate grade of inflammatory activity. The mean duration of complete remission in these patients was 8.5 years. METHODS: ANCAs were detected using indirect immunofluorescence and enzyme-linked immunosorbent assays (ELISAs). RESULTS: Only 13 (9%) of 137 patients with ulcerative colitis had ANCAs (5% had p-ANCAs). Three patients had previously undergone colectomy. In patients with Crohn's disease, ANCAs were observed in 17 of 110 patients (15%, 6% had p-ANCAs). Fifteen of these patients had colonic disease. CONCLUSION: In patients with ulcerative colitis free from inflammation for prolonged periods of time, ANCAs occurred less frequently than has previously been reported. Patients with Crohn's disease had the expected frequency of ANCA positivity, which for colonic Crohn's disease was comparable to that found in patients with ulcerative colitis. These findings suggest that the titre of ANCAs decreases with time in inactive disease and may be undetectable with conventional assays after several years of complete remission.

Adult↗
PubMed1995

[Toxic colitis. II. Personal experience].

The author presents his own experience with the diagnosis and treatment of 19 patients with acute manifestations of toxic colitis. Patients with ulcerative colitis developed toxic colitis in 11 instances. The second most frequent background for the development of toxic colitis was pseudomembranous colitis. Conservative treatment before 72 hours was successful only in two patients. Seventeen patients were operated at varying intervals after the onset of the disease (1-21 days) and subtotal colectomy was performed with ileostomy and a mucous fistula of the rectosigmoid. The lethality in the whole group was 10.5%. All patients who died (2) were from the group operated on the 5th-7th day, while in the groups operated on the 2nd-5th and 14th to 21st day there were no deaths. In the group two cases of carcinoma were detected.

Adolescent↗
PubMed1995

Bowel stricture due to ischemic colitis: report of three cases requiring surgery.

The diagnosis of ischemic colitis is challenging and still based upon a high index of suspicion. We report here, three patients affected by ischemic colitis causing stenosis and intestinal obstruction that required surgical treatment. Results of surgery in the three cases were not fair reflecting the high mortality and morbidity rate of ischemic colitis. However, the three cases showed peculiar features allowing us to make a few speculative considerations. Better results in the treatment of ischemic colitis might be achieved by means of a prompt recognition of the initial picture and through a better control of the many associated diseases, that represent the main risk factor for the development of ischemic colitis itself and for the bad prognosis of surgical treatment.

Aged↗
PubMed1979

Prevention of clindamycin-induced colitis in hamsters by Clostridium sordellii antitoxin.

Toxins produced by Clostridium difficile have been implicated in the etiology of antibiotic-induced colitis. Clostridium difficile antitoxin is not available, but recent studies have shown that toxins present in the feces of patients with this disease are neutralized by Clostridium sordellii antitoxin. We found that C. sordellii antitoxin neutralized toxins produced in broth cultures of either C. sordellii or C. difficile and that passive immunization with C. sordellii antitoxin before challenge with clindamycin prevented colitis in hamsters. Significantly fewer antitoxin-treated animals than unimmunized controls developed diarrhea and died with hemorrhagic colitis. Administration of 300 U of antitoxin parenterally either on the day of challenge with clindamycin or 24 hr later provided significant protection (25% mortality vs. 100% mortality in controls, P less than 0.01). None of eight animals given antitoxin (300 U) both on the day of challenge and 24 hr later died. Filtrates prepared from cecal contents of dead or killed hamsters were tested for toxicity by intraperitoneal injection into hamsters and by addition to monolayers of monkey kidney cells. Fecal filtrates from antitoxin-protected animals were not toxic in these assays, but filtrates from control animals were uniformly toxic. Passive immunization against clostridial toxins was protective against clindamycin-associated colitis in this model. This finding further substantiates the importance of these toxins in the pathogenesis of antibiotic-induced colitis.

Animals↗
PubMed1995

Collagenous and lymphocytic colitis: subject review and therapeutic alternatives.

OBJECTIVE: To review the published studies on collagenous and lymphocytic (microscopic) colitis with specific emphasis on clinical features, investigational studies, characteristic histology, possible pathogenesis, disease course, and empirical treatment. DESIGN: Comprehensive synopsis of the stated objective, prepared for the physician treating patients with collagenous or lymphocytic colitis. MATERIALS AND METHODS: The medical literature on collagenous and lymphocytic colitis. RESULTS: Collagenous and lymphocytic colitis are chronic diarrheal illnesses of indeterminate etiology that typically present in the late sixth or early seventh decade of life. These disorders may be distinct entities, although some data support the idea that they are only different manifestations of the same disease. The pathogenesis is unknown but may be on an inflammatory, possibly autoimmune, basis. Physical examination and investigational studies are normal or nonspecific, with fecal leukocytosis the only abnormality found in the majority of patients tested. Association with various gastrointestinal, autoimmune, and rheumatologic conditions has been observed in some patients. Clinical and occasional histologic response has been observed after treatment with anti-inflammatory agents such as 5-aminosalicylate and corticosteroids, and should be used when there is no response to symptomatic therapy. CONCLUSIONS: Collagenous and lymphocytic colitis are uncommon but important causes of chronic diarrhea which are important to diagnose and treat.

Algorithms↗
PubMed1995

Prolonged medical therapy for severe pediatric ulcerative colitis.

OBJECTIVES: The optimal timing of surgical intervention for severe ulcerative colitis remains uncertain. Numerous reports recommend surgery within 10-14 days if clinical remission is not achieved. We undertook a study to follow the clinical course and long-term follow-up of patients with severe ulcerative colitis treated medically for longer than 14 days (n = 11). METHODS: We performed a retrospective review of all patients admitted to the hospital with a diagnosis of severe ulcerative colitis who were treated for more than 14 days. RESULTS: Nine percent of patients (n = 1) required surgery during their hospitalization. Ninety-one percent of patients (n = 10, mean age 8.6 yr, 7 M, 3 F) treated with medical and nutritional therapy for more than 14 days went into clinical remission. Of these, only 10% (n = 1) ultimately required surgery; 60% remain in clinical remission up to 83 months posthospitalization (mean follow-up, 49.5 months), whereas 30% suffer from mild to moderate colitis (mean follow-up, 26.3 months). CONCLUSIONS: These results do not support the recommendation for colectomy for refractory severe ulcerative colitis if remission is not noted within 2 wk of hospitalization.

Adolescent↗
PubMed1995

Air enema radiology compared with leukocyte scintigraphy for imaging inflammation in active ulcerative colitis.

OBJECTIVE: To compare air enema radiology with a leukocyte scintigraphy technique using technetium-99m-hexamethyl propylene amine oxime-labelled leukocytes for imaging colonic inflammation in ulcerative colitis. DESIGN: Prospective study in a University hospital. One radiologist and one nuclear physician independently graded the degree of inflammation in six colon segments per patient using radiographs and leukocyte scans. PATIENTS: Twenty consecutive patients with symptoms of active ulcerative colitis requiring corticosteroids, inflammation on rigid sigmoidoscopy and a positive leukocyte scan above the rectum. RESULTS: Using air enema radiology, inflammation above the rectum was observed in 17 of the 20 patients. Eleven patients had the same extent of disease with both imaging techniques (total n = 5; extensive n = 3; distal n = 3). Seven patients had more widespread colitis using leukocyte scintigraphy. In the remaining two patients with extensive inflammation at scintigraphy, air enema films showed total colitis. When the colon was subdivided into six different segments, prediction of the presence of inflammation in individual segments was 0.88 for air enema radiology compared with leukocyte scintigraphy and 0.60 for the prediction of absence of inflammation. All segments with an irregular mucosal contour or ulceration on air enema films had intense inflammation at scintigraphy. CONCLUSIONS: In patients with active ulcerative colitis, air enema radiology underestimates the extent of inflammation because this investigation shows secondary patho-anatomical changes, while leukocyte scintigraphy visualizes the acute cellular infiltrate. In patients with more severe inflammation, there is excellent agreement between the two methods.

Adolescent↗