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[Diagnosis of colitis caused by cytomegalovirus infection in AIDS. Comparative value of total colonoscopy and rectosigmoidoscopy (apropos of 24 cases). AIDS GIT].

OBJECTIVES: To evaluate the respective diagnostic value of flexible rectosigmoidoscopy and colonoscopy in the cytomegalovirus colitis. METHODS: Twenty-four patients with AIDS were studied retrospectively. The entry criteria were: flexible rectosigmoidoscopy or colonoscopy, with 2 rectal and 2 caecal biopsies, presenting cytomegalovirus inclusions bodies linked to an inflammation at least on one colonic biopsy. RESULTS: Twenty-four patients had 29 colonoscopies. In 16 cases colonoscopy was performed to the caecum. The endoscopic findings of the 16 full colonoscopies were: 7 right colitis, 5 diffuse colitis, 2 bisegmentary colitis, 1 proctitis and 1 non endoscopic lesion. The histologic findings of the 16 full colonoscopies were: 5 cytomegalovirus inclusions on rectal biopsies and 16 on caecal biopsies. For the 13 incomplete colonoscopies, 11 had inclusions on rectal biopsies. So the flexible rectosigmoidoscopy was not sufficient to find inclusions 13 times out of 29. CONCLUSION: Our study indicates that in the cytomegalovirus colitis, inclusions predominate in the caecum, isolated right colitis exists and extra-colonic cytomegalovirus disease is not always found. For these reasons full colonoscopy is necessary for diagnosis in patients with normal flexible rectosigmoidoscopy.

AIDS-Related Opportunistic Infections↗

Paradoxical response to heparin in 10 patients with ulcerative colitis.

OBJECTIVES: A patient with ulcerative colitis refractory to standard therapy was treated with heparin for a deep vein thrombosis. Paradoxically, rectal bleeding did not increase; instead, his colitis rapidly went into remission. The same effect occurred when this patient was later treated for a pulmonary embolism. On the basis of these observations and reports of a hypercoagulable state in ulcerative colitis, heparin was tested as a therapeutic agent in nine additional patients. METHODS: Nine of the 10 patients had ulcerative colitis poorly controlled on sulfasalazine and prednisolone. Two had associated thromboembolic disease, and one was on no medication. Patients were started on heparin in hospital, taught to self-inject subcutaneously, and discharged to continue on 10,000 U of unfractionated heparin twice daily. Current doses of sulfasalazine were maintained; prednisolone was tapered and stopped. Patients were carefully monitored for adverse side-effects. Sections of colonic mucosa from nine patients were examined for intravascular thrombosis of the mucosal blood vessels. RESULTS: Nine patients became asymptomatic (normal stool frequency, no rectal bleeding) on combined heparin and sulfasalazine therapy; one patient had a partial improvement in symptoms. Highly significant statistical differences between pre- and posttreatment mean scores were found for all disease parameters. Intravascular fibrin thrombi were identified in sections from six of nine patients. No serious complications were associated with this use of heparin. CONCLUSIONS: The heparin-linked remission of ulcerative colitis, observed by chance in our first patient, was followed by similar responses in eight of nine further patients. This suggests that, used as described, heparin may have a role in treating refractory ulcerative colitis.

Adult↗

Psychological stress and disease activity in ulcerative colitis: a multidimensional cross-sectional study.

OBJECTIVES: It is not known whether any link exists between life stress and disease activity in ulcerative colitis; attempts to demonstrate one have been complicated by recall bias, distressing psychological consequences of disease, psychogenic symptom exaggeration, and an irritable bowel component of inflammatory bowel disease symptoms. We therefore studied the relationship between psychological measures and two different aspects of ulcerative colitis activity. METHODS: The relation of perceived stress, depression, state anxiety, trait anxiety, and life events with endoscopic appearance of the rectal mucosa was studied "blind" in 46 asymptomatic outpatients with known ulcerative colitis. The same measures were then examined in relation to subjective activity, comparing the group in clinical remission with 32 ulcerative colitis outpatients who reported symptoms. RESULTS: Among asymptomatic patients, the level of stress over the past 2 yr on the General Perceived Stress Questionnaire was higher in the 11 with mucosal abnormalities than in the 35 with a normal rectal mucosa (p = 0.004). Among the entire population, symptomatic patients were more likely to recall major life events in the previous 6 months than the asymptomatic group (p = .02). Adjustment for smoking and for duration of remission did not substantially alter these findings. CONCLUSIONS: Life stress is associated with both objective and subjective aspects of activity in ulcerative colitis. Although the association of life events with reported symptoms may be subject to recall bias, the association of perceived stress with rectal mucosal abnormalities in asymptomatic patients is strongly suggestive of a true link between psychological factors and ulcerative colitis activity.

Adult↗

K-ras mutations and p53 alterations in neoplastic and nonneoplastic lesions associated with longstanding ulcerative colitis.

We have analyzed K-ras mutations and p53 alterations in 39 tumor and nontumor samples taken from nine patients with longstanding ulcerative colitis and colorectal carcinoma. Two of nine invasive carcinomas contained a K-ras mutation. By a combination of immunohistochemistry and single-strand conformation polymorphism analysis, p53 alterations were found in three of nine carcinomas. Five of 13 dysplastic lesions harbored a mutated K-ras gene, even in the absence of detectable changes in associated invasive tumors. One single focus of dysplastic mucosa harbored concomitant K-ras and p53 gene alterations. In two patients, a K-ras mutation was detected in epithelial lesions considered to be devoid of malignant potential (villous regeneration, active colitis). Our results indicate that: 1) the prevalence of K-ras and p53 genetic alterations found in ulcerative colitis-associated colonic carcinomas appears to be lower than in sporadic carcinomas; 2) K-ras mutations can be detected in dysplasia, villous regeneration, and active colitis and affect a subpopulation of the cells composing the lesions; 3) diverse genetic alterations can be detected in the same patient and the dysplastic lesions can exhibit a different genotype than the carcinomas; and 4) at least part of active colitis and villous regeneration lesions should be considered as preneoplastic in ulcerative colitis.

Adult↗

[Long-term prognosis of patients with ulcerative colitis].

A regional inception cohort of 1161 ulcerative colitis patients was followed from diagnosis to the end of 1987. Follow-up rate for death and occurrence of cancer was 99.9%. Median observation time 11.7 years, range 0-26 years. One hundred and forty-one deaths were observed, 26 due to ulcerative colitis or complications thereof. No significant excess mortality was found after the first year, but in the year of diagnosis the relative risk of death was 2.4 (p < 0.001). The cumulative colectomy rate was 32.4% 25 years after diagnosis. The initial extent of disease significantly influenced the colectomy probability, being 35% in total colitis, 19% in substantial colitis and 9% in distal colitis within the first five years after diagnosis. Six patients developed colorectal cancer within the observation period. Compared to the expected number of 6.6 the relative risk for patients with ulcerative colitis was 0.9. The calculated cumulative cancer incidence was 3.1% after 25 years (95% confidence limits 0.0-6.8). The calculated lifetime risk (0 to 74 years) for development of colorectal cancer was 3.5% for the patients compared to 3.7% for the Danish population. We conclude that with an active approach to medical and surgical treatment as was practiced here, those patients who are left with their colon intact bear no significantly increased risk of colo-rectal malignancy.

Adolescent↗

Colonic mucus, smoking and ulcerative colitis.

Human colonic mucosal protection is not fully understood but may in part rely on a layer of mucus gel adherent to the mucosa. Ulcerative colitis may occur if mucosal protection breaks down. Two studies are presented, both of which relate to the aetiology of ulcerative colitis. First, a layer of adherent mucus gel was demonstrated by a simple, reliable method. Measurements of mucus layer thickness were made in freshly resected colonic specimens and shown to increase from a mean of 107 microns on the right colon to 155 microns in the rectum. In ulcerative colitis the layer is significantly thinner or absent, whereas in Crohn's disease the colonic mucus layer is significantly thicker. Second, the relationship between smoking and colitis is explored by a double-blind, randomised and placebo-controlled trial of transdermal nicotine in active disease. Significant clinical benefit was seen, indicating nicotine may be both useful therapeutically and the component of tobacco smoke that acts to protect against colitis. Since smoking and nicotine have actions on mucosae and mucus in other organs, it is argued that there is a mucus deficiency in ulcerative colitis that smoking acts to reverse.

Adult↗

[Surgical therapy of severe colitis].

Severe colitis, eventually complicated by toxic megacolon, perforation or massive hemorrhage still represents a potentially life threatening complication during the course of inflammatory bowel disease reaching a mortality of almost 40% if not operated in time. From 1.1.1973 until 30.4.1994 22 patients (13 men, 9 women, mean age 29 years) with either ulcerative colitis or Crohn's disease of the colon were operated on for severe colitis. Indications for operative treatment were as follows: 7 patients relapsed conservative medical treatment, 8 developed toxic megacolon and in 7 patients perforation occurred. Diagnosis was based on the clinical criterias first described by Turnbull. In 11 (50%) cases subtotal colectomy with an ileostomy and intrapelvic Hartmann's pouch was performed, in 4 (18%) patients a Turnbull's procedure was carried out with loop ileostomy and colostomies and in 3 (14%) cases a left hemicolectomy and transversostomy was applied. In two patients with Crohn's disease an ileocolic resection was done because of perforation, one received a subtotal colectomy and ileorectal anastomosis and one patient was operated by a right hemicolectomy and ileostomy. One patient with ulcerative colitis died, reaching a post-operative mortality of 4.5%. After an intervall of approximately 18 months in the 16 surviving patients with ulcerative colitis an ileal pouch-anal procedure could be done. Of the 5 patients with Crohn's disease one had to be operated on for recurrence, the other patients have been free of recurrent Crohn's disease for a follow-up time between 3 and 11 years. We conclude, provided early operative treatment is intended, that subtotal colectomy with Hartmann's pouch and ileostomy is the procedure of choice in patients with severe colitis.

Adult↗

Treatment of colitis in Behçet's disease with thalidomide.

A 40-year-old Turkish man on busulphan treatment for chronic myeloid leukaemia was hospitalized with steroid resistant (up to 100 mg prednisolone/24 h for over 4 weeks) colitis. On the basis of concomitant orogenital ulceration and unusual, deep punched out ulcers in the colon and smaller ulcers in the terminal ileum, Behçet's disease of the bowel, manifesting as ileocolitis, was diagnosed. Leukaemic infiltration, Crohn's colitis, neutropenic colitis and infectious colitis were excluded by histology and cultures. Treatment with colchicine 2 mg/day improved the orogenital ulcers but with only minor improvement of the colitis. Thalidomide treatment (400 mg/day), however, dramatically improved the colitis within 7 days: fever and diarrhoea disappearing. Colonoscopy after 4 weeks of treatment revealed previously giant ulcers practically healed.

Adult↗

Role of cytokines in the early stages of chronic colitis in TCR alpha-mutant mice.

Chronic colitis develops spontaneously in mice mutant for T-cell receptor alpha (TCR alpha) genes maintained in pathogen-free conditions. Our previous studies indicate that the cytokine imbalance caused by a lack of TCR alpha beta + T cells may be associated with the development of chronic colitis in TCR alpha-mutant (TCR alpha -/-) mice. The histologic changes of chronic colitis are recognizable by 3 to 4 months of age and are characterized by marked crypt cell hyperplasia and the presence of an inflammatory cell infiltrate. Because early events in the development of chronic colitis may be important in the pathogenesis of the disorder, we investigated the changes in the colon at a time when chronic colitis was not yet histologically recognizable. In vivo labeling with 5-bromo-2'-deoxyuridine revealed increased epithelial proliferation in the crypts by 6 to 8 weeks of age. There was an increase in number of T cells in the colon of TCR alpha -/- mice compared with that in TCR alpha +/- (heterozygous TCR alpha-mutant) mice after 6 weeks of age. The predominant T-cell subsets were CD4+, TCR alpha- beta +, and TCR gamma delta + cells. Reverse transcription-PCR and immunohistochemistry of the colonic mucosa obtained from TCR alpha -/- mice (> 6 weeks old) showed a marked increase of IL-1 alpha and IL-1 beta but not of TNF alpha or transforming growth factor beta-1 compared with TCR alpha +/- mice. In vivo neutralization of IL-1 alpha or IL-1 beta by specific mAb suppressed colonic epithelial proliferation and decreased colonic mucosal T-cell infiltration in 8-week-old TCR alpha -/- mice. These results provide direct evidence that overproduction of IL-1 alpha and IL-1 beta in the colonic mucosa may play an important role in the early stages of development of chronic colitis in TCR alpha -/- mice.

Animals↗

Endoscopic screening for dysplasia and mucosal aneuploidy in adolescents and young adults with childhood onset colitis.

OBJECTIVES: In adults, the premalignant nature of ulcerative colitis (UC) has long been accepted. Currently there is increasing concern that Crohn's disease (CD) may be equally premalignant. As a consequence, most adults with long-standing UC and many with chronic CD are enrolled in ongoing endoscopic cancer surveillance programs. In contrast, the risk of colonic cancer in adolescents and young adults with either form of colitis is less well recognized, and the need for dysplasia and cancer screening in this population has not been systematically evaluated. We therefore report the prospective results of colonoscopic cancer screening in such a young population. METHODS: Thirty-five adolescents and young adults with long-standing colitis (18 UC, 17 CD; 21 +/- 3 yr old, 11 +/- 3 yr colitis duration) underwent colonoscopic cancer screening. All had multiple biopsies for flow cytometry and light microscopy. RESULTS: Seven subjects had aneuploidy (3/18 UC, 4/17 CD). Of these seven, only two had dysplasia [one high grade (UC), one low grade (CD)]. One additional subject had indefinite dysplasia with normal flow cytometry. The remaining 27 subjects had both normal flow cytometry and light microscopy. Five of the seven aneuploid subjects underwent surgery within 1 yr of screening. Four, including both subjects with dysplasia, had no evidence of colon cancer at surgery. However, a 24-yr-old female with a 14-yr history of UC and no evidence of dysplasia or cancer at screening had a Dukes C adenocarcinoma. CONCLUSIONS: Adolescents and young adults with childhood onset UC or CD are at risk for aneuploidy, dysplasia, and colon cancer. Aneuploidy can be evident 10 yr after the onset of colitis and in patients as young as 16 yr of age. Therefore, the risk for colon cancer in patients with childhood onset colitis must be based on the duration of the illness, not on their chronological age. Incorporation of flow cytometry into an endoscopic screening protocol appears to enhance the ability to identify individuals at highest risk for colon cancer.

Adolescent↗

Evaluation of clinical patterns in ulcerative colitis: a long-term follow-up.

The aim of this prospective research was to compare, in a seven-year follow-up, the clinical outcome of ulcerative pancolitis with that of non-progressive ulcerative colitis. The activity of the disease was evaluated by a Clinical Activity Index and an Endoscopic Index. Of 112 cases of ulcerative colitis observed, 95 showed no change in extent and were studied as examples of non-progressive UC, and in this group the extension of the disease was: pancolitis in 19%, left-sided colitis in 39%, proctosigmoiditis in 17% and proctitis in 25%. A colectomy had to be performed in 5%. None of the enrolled cases developed a cancer during the follow-up. The patients with ulcerative pancolitis or left-sided colitis were treated with 5-ASA 1.6 g/day in a delayed-release formulation, while the cases with proctosigmoiditis or proctitis were treated with 5-ASA enemas 4 g/day. The cases with more than one relapse/year were 39%. The proportion of patients with only one relapse/year was 53%. The patients with steady remission for all the seven years of the trial were only 8%, but with a statistically significant difference between the groups with initial diagnosis of proctosigmoiditis or proctitis and the group with initial diagnosis of pancolitis or left-sided colitis (12% versus 5%). Among the cases with continuous remission, 37% showed colonic alterations, with an endoscopic score higher than 4 but a clinical score less than 6. Side-effects were observed in 6% patients but without treatment withdrawal. Non-progressive ulcerative colitis throughout the colon has a relatively good prognosis which seems to be independent of the location of the disease, even if we have found a statistically significant higher percentage of cases with steady remission among the patients with more distal disease.

Administration, Oral↗

Beneficial effect of ursodeoxycholic acid on mucosal damage in trinitrobenzene sulphonic acid-induced colitis.

BACKGROUND: Recently we observed that ursodeoxycholic acid (UDCA) ameliorates an experimental small intestinal inflammation induced by indomethacin in the rat. In this study, we have tested whether ursodeoxycholic acid also reduces mucosal damage in the bile-independent trinitrobenzene sulphonic acid (TNB) model of experimental colitis. METHODS: Intestinal inflammation (colitis) was induced in male Sprague-Dawley rats (250-300 g) by intracolonic administration of TNB (30 mg in 50% ethanol). Rats were treated with UDCA (10 mg/kg) either for 3 days starting with the administration of TNB for an acute inflammation (n = 11) or for 8 days starting one day after induction of colitis related to a more acute/chronic inflammation (n = 11). Rats were sacrificed at day 3 or day 9, respectively. Healing of induced colitis was assessed by macroscopic and blinded microscopic analysis as well as by measurement of bowel wet weight, daily body weight, and myeloperoxidase activity. All examinations were separately performed in three colon segments (S1 3-5 cm, S2 5.5-8 cm and S3 8.5-11 cm from anus). RESULTS: UDCA treatment significantly reduced macroscopically and microscopically detectable injury in acute inflammation in segments 1 and 2. The colitis-rats with acute/chronic inflammation had less marked mucosal damage. Nevertheless, UDCA treatment led to a significant decrease of visible injury parameters which was seen exclusively at the area of maximal ulceration (S2). Furthermore, a significant increase in body weight of UDCA-treated TNB rats compared to controls from day 5 on was found. CONCLUSION: Ursodeoxycholic acid attenuates the severity of acute inflammation and inhibits the development of acute/chronic inflammation predominantly around the area of maximal ulceration in TNB-induced colitis. In addition to our previous studies and results in indomethacin induced enteritis, these data may provide a rationale for studying how UDCA modulates functions of immune cells in the colonic mucosa.

Animals↗

Substance P and vasoactive intestinal polypeptide but not calcitonin gene-related peptide concentrations are reduced in patients with moderate and severe ulcerative colitis.

BACKGROUND AND AIMS: Ulcerative colitis is a chronic inflammatory condition characterized by an altered intestinal immunoinflammatory response. Since increasing evidence indicates that neuropeptides play a key role in the regulation of gastrointestinal immune function, the aims of this study were: a) to determine tissue and plasma levels of Vasoactive Intestinal Polypeptide, Substance P, and Calcitonin Gene-Related Peptide in patients with ulcerative colitis, and b) to ascertain whether a relationship exists between tissue concentrations of neuropeptides and the histological grading of mucosal inflammation. METHODS: A total of 29 patients with active and 39 with inactive ulcerative colitis, and 16 control subjects took part in the study. Biopsy specimens of colonic mucosa and blood samples were obtained from each subject, and neuropeptide concentrations were measured by sensitive and specific radioimmunoassays. RESULTS: Both Vasoactive Intestinal Polypeptide and Substance P concentrations were found to be significantly reduced in endoscopic biopsy specimens of patients with ulcerative colitis compared to controls (p < 0.01 and p = 0.05, respectively), and the reduction appeared to be related to the degree of mucosal inflammation; in contrast, Calcitonin Gene-Related Peptide tissue levels were unchanged. In addition, there was no significant difference in the neuropeptide plasma levels between ulcerative colitis patients and control subjects. CONCLUSIONS: Taken together, our results suggest that the reduction of Vasoactive Intestinal Polypeptide and Substance P is probably a secondary phenomenon, correlated with the degree of mucosal inflammation; whatever the mechanism, the decreased availability of these neuropeptides in the local microenvironment may play an important role in the pathogenesis of ulcerative colitis, by affecting many components of the normal immune response. Moreover, based on our data, the measurement of neuropeptide plasma concentrations does not appear to be a useful tool to monitor disease activity.

Adult↗

The clinical significance of a biopsy-based diagnosis of focal active colitis: a clinicopathologic study of 31 cases.

Focal active colitis (FAC) is a common pattern of injury in colorectal biopsy specimens. Recently, FAC was found to be a marker of an infectious colitis-like diarrheal illness and ischemic colitis but not of Crohn's disease. We evaluated 31 cases of FAC at the Cleveland Clinic Foundation, Cleveland. Ohio, between 1982 and 1992, to assess the clinical significance of this histologic finding. We evaluated the degree of neutrophil-mediated crypt epithelial injury, the degree of neutrophil-mediated surface epithelial injury, and the lamina propria cellularity and cell type. In each biopsy specimen, all of the above features were scored as 1+ (involving < 10%), 2+ (10-25%), or 3+ (26-50%) of the specimen. Clinical follow-up for the 31 patients ranged from 1 to 51 months (mean, 26 mo). Clinical diagnoses included infectious-type colitis (15 cases, 48%); incidental FAC (9 cases, 29%), occurring in asymptomatic patients undergoing screening for colonic neoplasia; ischemic colitis (3 cases, 10%); and Crohn's disease (4 cases, 13%). Histologically, all of the cases had some degree of cryptitis, and 24 (77%) of the 31 had neutrophil-mediated surface epithelial injury. In 13 (42%) of the 31, there was an expansion of the lamina propria by neutrophils, in 12 (39%) by eosinophils, and in 11 (35%) by plasma cells. None of the histologic features correlated with specific clinical diagnostic categories (Fisher's exact test). In conclusion, FAC most commonly correlates clinically with an infectious-type of colitis. On occasion, FAC might be a harbinger of Crohn's disease. Histologic features are not useful in predicting specific clinical diagnoses as a correlate to FAC.

Bacterial Infections↗

Effect of chronic nicotine administration on trinitrobenzene sulphonic acid-induced colitis.

BACKGROUND: Smoking, probably due to nicotine, has a bivalent effect on inflammatory bowel disease, ameliorating disease activity in ulcerative colitis and with a deleterious effect on Crohn's disease. The effect of nicotine patches in ulcerative colitis is controversial. AIM: To investigate the effect of chronic nicotine use in a rat model of colitis. METHODS: Colitis was induced in Sprague-Dawley rats by rectal administration of 30 mg trinitrobenzene sulphonic acid (TNBS) in 50% ethanol. Nicotine was dissolved in drinking water (2.5, 12.5, 25 and 250 microg/ml), with rats drinking ad libitum. Nicotine administration started 10 days prior to damage induction and had no effect on weight gain or daily food intake of rats. Rats were sacrificed 1 and 5 days after TNBS administration, their colons resected, rinsed, weighed, damage assessed macroscopically (mm2) and microscopically and tissue processed for myeloperoxidase (MPO) and nitric oxide synthase (NOS) activities, leukotriene B4 (LTB4), prostaglandin E2 (PGE2) generation and interleukin-1 (IL-1) serum levels. RESULTS: Nicotine, by itself, caused no damage to the colon. Nicotine had a dose-dependent bivalent effect on colitis, significantly reducing macroscopic damage from 983 +/- 10 mm2 on TNBS alone to 429 +/- 118 mm2 on TNBS plus 12.5 microg/ml of nicotine, and escalating to 1086 +/- 262 mm2 on 250 microg/ml of nicotine. Segmental weight declined significantly (from 2.4 +/- 0.2 to 1.65 +/- 0.20 g/10 cm), on 12.5 microg/ml nicotine, as did MPO activity (from 3.2 +/- 0.4 to 0.7 +/- 0.1 units/g). All these parameters returned to the levels of TNBS alone when the dose of nicotine was increased to 250 microg/ml. Nicotine had no effect on NOS activity, PGE2 generation and serum IL-1 levels, but increased LTB4 generation. CONCLUSIONS: Nicotine has a dose-dependent bivalent effect on TNBS-induced colitis which is not due to reduction in IL-1 serum levels or PGE2 generation, and is not NOS-mediated.

Animals↗

[Interleukin-6 and interferon-gamma release from blood mononuclear cells and colonic mucosa from patients with ulcerative colitis].

BACKGROUND: Cytokines are involved in the pathogenesis of inflammatory bowel diseases such as ulcerative colitis and Crohn disease. AIM: To measure cytokine release by mononuclear cells of patients with ulcerative colitis. PATIENTS AND METHODS: Twelve patients subjected to a diagnostic colonoscopy were studied. Six had an ulcerative colitis and six did not have inflammatory changes in the colonic mucosa and were considered as control. Mononuclear cells were isolated from biopsies of colonic mucosa and from peripheral blood cultivated during 48 hours with pokeweed mitogen, and Interleukin 6 and interferon-gamma were measured in their supernatants. RESULTS: In patients with ulcerative colitis, interleukin 6 secretion by peripheral blood mononuclear cells was higher than in control subjects in the basal period (2212 +/- 424 and 443 +/- 174 pg/ml respectively p = 0.03) and after stimulation with pokeweed mitogen (16,328 +/- 1275 and 5462 +/- 322 pg/ml respectively p = 0.03). No differences in interleukin 6 secretion by colonic mucosa mononuclear cells were observed. Unstimulated cells did not liberate interferon-gamma. The secretion of this lymphokine by stimulated colonic mucosa cells was lower in patients with ulcerative colitis than in controls (1571 +/- 216 and 7953 +/- 389 pg/ml respectively p = 0.03). CONCLUSIONS: Local and systemic changes in interleukin 6 and interferon-gamma secretion occur in patients with ulcerative colitis. These changes could be related to the development of the disease.

Adult↗

The radiological differentiation between ulcerative and granulomatous colitis by double contrast radiology.

The purpose of this report is to illustrate the value of the double contrast technic for the detection of early changes of colitis and for the differentiation between ulcerative and granulomatous colitis. Fifty consecutive patients with radiologically-diagnosed nonspecific colitis are included and the radiographs, endoscopic and pathologic reports and photographs were reviewed. On radiological grounds ulcerative colitis were diagnosed in 23 patients and granulomatous colitis in 27 patients. There were no radiologically indeterminate cases. Follow-up information was obtained by colectomy in nine patients, colonoscopy in nine patients and sigmoidoscopy in the remainder. In no case did the endoscopic or pathologic diagnosis conflict with the radiological diagnosis. With the double contrast technic, very fine mucosal detail can be seen including features such as granular mucosa, "aphthoid" ulcers and discontinuous disease which are not demonstrable by the conventional single contrast barium enema. This detailed mapping of the nature and extent of disease facilitates the differential diagnosis between ulcerative and granulomatous colitis.

Colitis, Ulcerative↗

Demonstration of an epithelial antigen in colon by means of fluorescent antibodies from children with ulcerative colitis.

Thirteen sera from children with ulcerative colitis were examined for antibodies reacting with constituents of human colonic tissue by means of immunofluorescent methods. 3 out of 10 sera reacted positively when tested by the direct staining method while 6 out of 13 reacted positively when tested by the indirect method with conjugates of rabbit anti-human gamma globulin. The specificity of the reactions could be confirmed by inhibition tests. 16 sera from healthy children and adults yielded completely negative results. The staining capacity of various sera was correlated to their hemagglutinating titer when they were tested with sheep erythrocytes, coated with phenol-water extract of human colon. Absorption experiments indicated that the stainable antigen was also present in the extracts used for the hemagglutination experiments. In unfixed tissue sections, fluorescent antibodies were adsorbed onto the epithelial cells of the mucosa. Adsorption on epithelial basement membranes could not be demonstrated. Fluorescent H agglutinins, isolated from eel serum, were adsorbed onto the same mucosal structures of human colon (blood group O) as the antibodies in the sera of patients with ulcerative colitis. However, any immunological relationship between H substance and the colonic antigen of ulcerative colitis could be ruled out by cross-inhibition and hemagglutination inhibition experiments. Fluorescent serum from patients with rheumatoid arthritis also stained sections of human colon but the localization of the stainable antigens was different from that visualized with the ulcerative colitis sera. Inhibition experiments indicated that the rheumatoid arthritis serum contained antibodies staining colon antigens different from those reacting with antibodies in the ulcerative colitis sera. Sera from patients with systemic lupus erythematosus or with the nephrotic syndrome, which all hemagglutinated erythrocytes coated with colon extract, did not stain the sections of the colon tissue either because of suboptimal antibody concentration or because of a difference in type or localization of the antigen.

Adult↗