Lymphogranuloma venereum: biopsy, serology, and molecular biology

The case of a patient ulcerative colitis involving an autoimmune base who was treated with recombinant alpha-2b interferon for presenting chronic active hepatitis in relation to virus C is reported. Such treatment was achieved in addition to improving the hepatic disease normalizing the transaminases control the outbreak of ulcerative colitis that the patient was presenting from some days before beginning the treatment. Various aspects are discussed related to the autoimmunity in the ulcerative colitis and in the chronic C hepatitis and the exarcebation of autoimmune phenomena which may lead to interferon therapeutic. As a basis for the above and the review of the literature, we concluded that the existence of ulcerative colitis does not contraindicate the use of alpha-2b interferon in patient with chronic hepatitis, although special control of the disease should be carried out during the treatment period.     

A method for activity staining of peroxidase and beta-1,3-glucanase isozymes in polyacrylamide electrophoresis gels

Various mechanisms have been proposed for the aetiology of inflammation in ileal pouches following restorative proctocolectomy. It is proposed that many of these processes may be involved in the pathogenesis of ulcerative colitis, and therefore pouchitis may be used to study pathogenesis and treatment of inflammatory bowel disease in general and, in particular, ulcerative colitis.     

Anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease with special attention for IgA-class antibodies

Perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) of the IgG class have been reported in inflammatory bowel disease, mainly in ulcerative colitis. Since this disease affects the gastrointestinal tract, we determined whether IgA class ANCA were present in inflammatory bowel disease. We used an indirect immunofluorescence assay for IgG and IgA ANCA testing. Sera from 34 patients with Crohn's disease and 29 patients with ulcerative colitis were collected together with clinical and laboratory data. We found IgA class ANCA of a perinuclear type in 52% of patients with ulcerative colitis and in 9% of Crohn's disease patients. There was a significant association between the presence of IgA ANCA and the occurrence of blood in the feces in the ulcerative colitis group (P = 0.03). IgG ANCA was found in 56% of patients with ulcerative colitis and in 7% of patients with Crohn's disease. Because of partial overlap between IgG and IgA ANCA positivity, the sensitivity of ANCA testing in ulcerative colitis increased from 56% up to 78% by combining IgG and IgA assays. In conclusion, IgA ANCA occurs with a high prevalence in ulcerative colitis. Moreover there is a possible relationship between IgA ANCA and disease activity in ulcerative colitis.     

Incidence of inflammatory bowel diseases in the department of Puy-de-D?me in 1993 and 1994. EPIMICI. Epidémiologie des Maladies Inflammatoires Cryptogenetiques de l'Intestin group

The aim of this prospective epidemiological study was to investigate the incidence of Inflammatory Bowel Disease in the Puy-de-D?me county using the same methodology as EPIMAD's registry. METHODS: From 01/01/93 to 31/12/94, each gastroenterologist (n = 22) collected patients consulting for the first time with clinical symptoms compatible with inflammatory bowel disease. Data were reported on a questionnaire by an interviewer practitioner. The final diagnosis of Crohn's disease and ulcerative colitis was made in a blind manner by two expert gastroenterologists and recorded according to the Calkin's criteria as definite, probable, or possible diagnosis, or unclassifiable chronic colitis or acute colitis. RESULTS: 167 new cases were identified: 112 (67.1%) inflammatory bowel disease for the combined group of definite and probable cases with 79 Crohn's disease (70.5%), 29 ulcerative colitis (25.9%) of which 11 ulcerative proctitis (37.9%), 4 unclassifiable chronic colitis (3.6%) and 55 acute colitis (32.9%). The crude and age-adjusted incidence (per 10(5)/year) was respectively 6.6 and 5.7 for Crohn's disease and 2.4 and 1.9 for ulcerative colitis. The highest age-specific incidence rate for Crohn's disease was between 40-49 years (14.1) and for ulcerative colitis between 80-89 years (6.8). The female/male ratio was 0.8 for Crohn's disease and 1.1 for ulcerative colitis. The median age at the time of diagnosis was 42.6 years for Crohn's disease and 35.3 years for ulcerative colitis. CONCLUSIONS: These preliminary findings revealed a high incidence of Crohn's disease and low of ulcerative colitis in this county. However, these results must be managed carefully because these data were recorded only on two years and the inflammatory bowel disease classified possible and acute colitis require a follow-up.     

Association between inflammatory bowel disease and sarcoidosis. Report of two cases and review of the literature

BACKGROUND: Common etiopathogenic factors may explain the association of systemic sarcoidosis with inflammatory bowel disease. METHODS: We report two cases of such an association: one of sarcoidosis that developed 2 years after proctocolectomy for ulcerative colitis and one of sarcoidosis and Crohn's colitis. Factors like increased cellular immunity or circulating immunocomplexes or autoantibodies may have a role. Exogenous agents or familiarity may also be involved. CONCLUSIONS: It is postulated that the association between sarcoidosis and inflammatory bowel disease (both ulcerative colitis and Crohn's disease) does not occur by chance alone and that the two conditions may share some genetic or immunologic alterations. The two diseases, however, follow an independent clinical course.     

The majority of myeloid-antigen-positive (My+) childhood B-cell precursor acute lymphoblastic leukaemias express TEL-AML1 fusion transcripts

BACKGROUND & AIMS: Crohn's disease and ulcerative colitis show a familial aggregation. In both diseases, anti-goblet cell autoantibodies (GABs) have been described. The aim of this study was to define the role of GABs in the pathogenesis of inflammatory bowel disease. METHODS: The study population comprised 61 patients with ulcerative colitis, 76 patients with Crohn's disease, 101 first-degree relatives of patients with ulcerative colitis, and 105 first-degree relatives of patients with Crohn's disease. Thirty-five patients with infectious enterocolitis and 56 healthy unrelated subjects served as controls. Autoantibodies were detected by indirect immunofluorescence. RESULTS: Thirty-nine percent of patients with ulcerative colitis (24 of 61) and 30% of patients with Crohn's disease (23 of 76) were positive for GABs. GABs were detected in 21% (21 of 101) of first-degree relatives of patients with ulcerative colitis and in 19% (20 of 105) of first-degree relatives of patients with Crohn's disease. In patients with infectious enterocolitis and in healthy controls, GABs were seen in 3% (1 of 35) and 2% (1 of 56), respectively. The differences between control groups and both groups of patients or their first-degree relatives were significant. CONCLUSIONS: The high prevalence in first-degree relatives suggests that GABs may represent a marker characterizing susceptibility to inflammatory bowel disease.     

Incidence of inflammatory bowel disease in northern France (1988-1990)

There were no data concerning the incidence of inflammatory bowel disease (IBD) in France. The aim of this study was to investigate the incidence of Crohn's disease and ulcerative colitis in northern France. This prospective population based study was realised through the gastroenterologists of the region Nord-Pas de Calais and the Somme Department. Each gastroenterologist referred patients consulting for the first time with clinical symptoms compatible with IBD. Data were collected by an interviewer practitioner present at the gastroenterologist's consulting room. Two independent expert gastroenterologists assessed each case in a blind manner and made a final diagnosis of Crohn's disease, ulcerative colitis, ulcerative proctitis, or unclassifiable chronic colitis. From 1988 to 1990, 1291 cases of IBD were recorded: 674 (52%) Crohn's disease, 466 (36%) ulcerative colitis including 162 proctitis (35%), and 151 (12%) unclassifiable chronic colitis. The mean annual incidence was 4.9 per 100,000 for Crohn's disease and 3.2 for ulcerative colitis. The sex ratio F/M was 1.3 for Crohn's disease and 0.8 for ulcerative colitis. The highest age specific incidence rate for Crohn's disease was between 20 and 29 years: 13.1 for women and 9.8 for men. The highest age specific incidence rate for ulcerative colitis was between 20 and 39 years: 5.5 for women and 6.5 for men. This first French prospective study has shown an incidence rate for Crohn's disease comparable with that seen in north European studies but lower than that seen for ulcerative colitis. These results could be related to the different environmental factors or the genetic background of the population studied, or both.     

Growth suppression mediated by transfection of wild-type hMLH1 in human cancer cells expressing endogenous truncated hMLH1 protein

Eosinophils contribute to the inflammatory process in a variety of chronic inflammatory bowel diseases. Ketotifen is beneficial in experimental models of colitis and in patients with eosinophilic gastroenteritis. Therefore, we investigated the efficacy of ketotifen therapy for the treatment of active ulcerative colitis. Children with newly or previously diagnosed ulcerative colitis with mild-moderate disease activity were treated with ketotifen at a dosage of 4 mg daily for eight weeks. Efficacy was determined by a physician disease severity index and by endoscopic and histologic examinations. Ten patients were enrolled. Symptoms improved in four patients and resolved completely in one patient. There was endoscopic improvement in three patients and histologic improvement in one. Increased eosinophils on rectal biopsy at entry were present in two of the responders. Five patients withdrew due to a lack of symptomatic improvement. No adverse events were identified. Low-dose ketotifen offers a limited therapeutic advantage in active ulcerative colitis that may be enhanced in the subgroup of patients with a high eosinophil count in the colonic mucosa. Further study of therapeutic efficacy with increased dosages of the mast cell stabilizer for acute and maintenance therapy is warranted.     

Guidelines for the treatment of ulcerative colitis in remission

The role is reviewed of sulphasalazine, 5-aminosalicylic acid (5-ASA), immunosuppressive agents and corticosteroids in the maintenance treatment of ulcerative colitis in remission. Sulphasalazine and oral 5-ASA are the drugs of first choice in preventing relapses for patients suffering from intermittent chronic ulcerative colitis. Rectally administered 5-ASA may be a valid alternative for treating patients with proctitis and left-sided ulcerative colitis. The optimal dosage of oral 5-ASA in the maintenance therapy of ulcerative colitis in remission is not clear. However, there is evidence that a higher dose of 5-ASA is more effective than low dosage in preventing relapses in patients in remission. For patients with chronically active or steroid-dependent ulcerative colitis who have achieved remission while taking immunosuppressants, continuing azathioprine or 6-mercaptopurine is indicated. Existing data cast doubts as to whether or not continuous maintenance is still necessary in patients suffering from intermittent chronic ulcerative colitis with prolonged endoscopic, clinical and histological remission.     

Suppression of male-specific cytochrome P450 isoforms by bisphenol A in rat liver

IBD results from the interaction of genetic and environmental factors (e.g., smoking). Clinical suspicion is the key to diagnosis, which then rests on colonoscopy, histopathological examination of multiple biopsy specimens, small bowel barium radiology and faecal examination. The primary goal of treatment is remission--histological in ulcerative colitis and symptomatic in Crohn's disease. Treating active disease and maintaining remission require different approaches. For active disease, short term corticosteroids are the mainstay of treatment, while immunosuppressive drugs are important in chronically active disease. For maintenance, mesalazine-delivering drugs and immunosuppressive agents are efficacious in both ulcerative colitis and Crohn's disease; patients with Crohn's disease should not smoke.     

Cytokine production from colonic T cells in patients with ulcerative colitis with and without primary sclerosing cholangitis

PURPOSE: Only five percent of all patients with ulcerative colitis develop primary sclerosing cholangitis. T cells accumulate at the sites of the colonic and bile duct inflammation in both ulcerative colitis and primary sclerosing cholangitis. T helper cell populations comprise functionally distinct subsets characterized by the cytokines they produce. Several alterations in cytokine production have been described in patients with ulcerative colitis. The aim of this study was to investigate possible differences in T helper subsets and cytokine production in peripheral blood and colonic mucosa among ulcerative colitis patients with and without primary sclerosing cholangitis. METHODS: Eleven patients with primary sclerosing cholangitis and extensive ulcerative colitis, 11 patients with extensive ulcerative colitis and no liver disease, and 5 patients without any history of liver disease who underwent routine colonoscopy because of previous polypectomy were included in the study. Colonoscopy with multiple biopsies was performed on all patients. Lamina propria mononuclear cells and peripheral blood mononuclear cells were isolated. A modified version of solid-phase enzyme-linked immunospot assay was used for the separate counting of cells producing interferon-gamma, interleukin-2 (T helper 1), and interleukin-4 (T helper 2). RESULTS: No differences in spontaneous production of cytokines from peripheral blood mononuclear cells was found among the three groups. Patients with primary sclerosing cholangitis compared with patients with ulcerative colitis without liver disease showed a significant increase in the number of cells secreting interferon-gamma after purified protein derivative stimulation (P < 0.02). More cells secreting interferon-gamma were found in the two ulcerative colitis groups than in the cell populations from healthy controls (P < 0.03). The number of cells secreting interferon-gamma in the primary sclerosing cholangitis group was significantly lower than in the ulcerative colitis group without liver disease (P < 0.04). The number of cells secreting interleukin-4 was lower in the primary sclerosing cholangitis group than among the patients with ulcerative colitis only (P = 0.05). CONCLUSION: Isolated lymphocytes from colonic mucosa differ in cytokine production in patients with ulcerative colitis with and without primary sclerosing cholangitis.     

Antineutrophil cytoplasmic antibodies in inflammatory bowel disease: diagnostic tool or research procedure?

Antineutrophil cytoplasmic antibodies, initially detected in the sera of patients with Wegener's granulomatosis and other forms of systemic vasculitides, have also been observed in patients with inflammatory bowel disease, with a higher prevalence in ulcerative colitis. In this study, we investigated the prevalence of these antibodies in the sera of 42 patients with ulcerative colitis and 48 patients with Crohn's disease, and the possible correlations with disease activity and extent, extraintestinal complications, and therapy. Antineutrophil cytoplasmic antibodies were found in 30 out of the 42 patients with ulcerative colitis (71.4%); only 16 out of the 48 patients (33.3%) with Crohn's disease were positive (p < 0.001), and the prevalent pattern was perinuclear. No correlations with disease activity and extent, extraintestinal complications, or surgical or medical treatment were found. Our data indicate that in the case of inflammatory bowel disease, the search for antineutrophil cytoplasmic antibodies still remains a research procedure and cannot be used for clinical diagnosis.     

Interleukin-1 receptor antagonist in differential diagnosis of inflammatory bowel diseases

BACKGROUND: Immunoregulatory properties of cytokines may mediate disordered inflammatory events in inflammatory bowel diseases (IBDs). On the basis of data obtained in experimental colitis, the hypothesis has been advanced that in IBD the balance between interleukin-1 (IL-1) and the naturally occurring IL-1 receptor antagonist (IL-1ra) might influence disease expression. OBJECTIVE: We studied the profiles of IL-1ra and acute phase proteins produced by activated macrophages to determine whether the level of IL-1ra in peripheral blood is a marker of disease activity in IBD and a possible differential diagnostic marker. PATIENTS AND METHODS: Levels of IL-1ra, serum neopterin, urinary neopterin, alpha 1-glycoprotein and C-reactive protein (CRP) were measured in 80 patients with ulcerative colitis, Crohn's disease or infectious colitis. RESULTS: Levels of IL-1ra were markedly increased in patients with active ulcerative colitis or active Crohn's disease compared with those in patients with infectious colitis. Patients with active Crohn's disease had significantly higher serum IL-1ra levels than patients with active ulcerative colitis. Moreover, a positive correlation was found between levels of C-reactive protein, alpha 1-glycoprotein, and serum neopterin and the level of IL-1ra in active Crohn's disease but not in active ulcerative colitis, strongly suggesting that the pathogenesis of the two conditions differs. CONCLUSION: Levels of IL-1ra in the peripheral blood of patients with IBD are of clinical relevance, representing a potent marker of disease activity and a possible differential diagnostic marker.     

Systemic recombinant human interferon-beta treatment of relapsing-remitting multiple sclerosis: pilot study analysis and six-year follow-up

The role of the spleen in patients with ulcerative colitis and Crohn's disease was assessed by counting pitted erythrocytes with differential interference microscopy and by splenic ultrasound. The findings were compared with those from age- and sex-matched controls and a group of splenectomized patients. The incidence of hyposplenism was lower than previously reported, being found in six of 29 patients with ulcerative colitis (of whom five had relapsed pancolitis and one had quiescent pancolitis) and two of 21 patients with Crohn's disease. Pitted erythrocyte counts were significantly higher in patients with ulcerative colitis compared with age- and sex-matched controls (p < 0.001), but there was no difference in counts between patients with Crohn's disease and controls. Patients with relapsed but not quiescent ulcerative colitis had significantly smaller spleens than controls. Patients with the highest pitted erythrocyte counts had the smallest spleens on ultrasound. More effective medical and surgical therapy may account for the lower incidence of functional hyposplenism observed in this study. Nonetheless, patients may show marked hyposplenism and remain at risk of overwhelming infection and operative complications. Differential interference microscopy is a simple technique that can be used to assess splenic function in patients thought to be susceptible to infection.     

Ulcerative colitis and intestinal bleeding

Ulcerative colitis is a nonspecific inflammatory disease of large intestine. Its inflammation is limited to intestinal mucosa. The most essential symptom is hematochezia, bloody stool and intestinal bleeding. Differential diagnosis among diseases having intestinal bleeding is clinically important. These diseases include Crohn disease, ischemic colitis, intestinal Beh?et disease, Enterohemorrhagic E. coli including O157, antibiotics associated hemorrhagic colitis and so on. Drugs for the treatment of ulcerative colitis are sulphapyridine, 5-aminosalicylic acid, prednisolone, betamethasone and immunosuppressive drugs. Recently, leukocytapheresis and massive immunoglobulin 7S treatment are available for the treatment of ulcerative colitis.     

Ulcerative colitis with skip lesions at the mouth of the appendix: a clinical study

OBJECTIVE: We examined the clinical characteristics of ulcerative colitis patients who demonstrated endoscopically discontinuous lesions at the mouth of the appendix. METHODS: Of patients with initial or recurrent active ulcerative colitis who underwent total colonoscopy during the past 3 yr at Osaka City General Hospital, we selected those who had skip lesions in the mouth of the appendix before treatment, and examined their gender, age, disease type, sites of lesions, inflammatory reaction, severity of disease, effects of treatment, and posttreatment course. RESULTS: Discontinuous lesions at the mouth of the appendix were found in 10 patients, who had the following common clinical features: the major lesion was usually present in the lower part of the large bowel including the rectum, many of the patients had suffered an initial attack only, all patients had mild disease, and many of the patients responded quite satisfactorily to treatment with salicylazosulfapyridine. CONCLUSION: Numerous patients with ulcerative colitis with discontinuous lesions at the mouth of the appendix were observed and their clinical characteristics were examined. Determination of the clinical significance of skip lesions in the appendix will contribute to elucidation of the pathogenesis of ulcerative colitis.     

Cytomegalovirus as the cause of toxic dilatation of the colon

Toxic dilatation of the colon is sometimes a complication which occurs during exacerbations of inflammatory bowel disease. It often requires immediate surgical intervention. We describe here a male patient with known ulcerative colitis who was investigated for fever of unknown cause, diarrhoea, and general illness. Upon admission he had only modest symptoms of colitis and received no immunosuppressive treatment. The condition worsened considerably, and subsequent colonoscopy demonstrated widespread lesions compatible with viral disease, but not with ulcerative colitis. Antiviral treatment for cytomegalovirus was started immediately, but progression of the condition with toxic dilatation called for a rapid colectomy. Histological examination showed widespread lesions compatible with cytomegalovirus infection. This clinical picture is rarely seen in immunocompetent patients.     

Surgery for inflammatory bowel disease in Singapore

Inflammatory bowel disease is uncommon in Asians and reports of surgery in these populations are rare. Eighty-two patients with inflammatory bowel disease were seen in the Department of Colorectal Surgery over a five-year period (1989-1994). Twenty-three patients underwent surgery for their disease. There were 12 males and 11 females with 16 Chinese, 4 Indians and 3 Malays. Twelve had Crohn's disease and 11, ulcerative colitis. The majority of patients with Crohn's disease had emergency surgery for bleeding, perforation, abdominal masses and intestinal fistulae. Fifty percent of these had the diagnosis made intraoperatively or post-operatively. Surgery for ulcerative colitis was indicated because of multiple relapses, non-response to medical treatment, side effects of therapy or malignant change. The median age at surgery of patients with Crohn's disease and ulcerative colitis was 39 years (range 24-84) and 40 (range 18-60) respectively. The median follow-up was 22.4 months (range 9-50). The results of surgical therapy in these patients show that surgery when indicated can be done with minimum morbidity and mortality.     

Lipid A antibody titers in Crohn's disease (author's transl)

Lipid A antibody titers and O antibody titers against E. coli were determined in 18 patients with Crohn's disease, 28 patients with ulcerative colitis, 24 patients with acute enteritis and in 68 healthy adults. The patients with Crohn's disease showed a statistically significant elevation of the lipid A antibody titers and of the O antibody titers against E. coli compared with each of the three other groups investigated. The results could be indicative of bacterial involvement in the pathogenesis of Crohn's disease. The determination of lipid A antibody titers may be useful for the differential diagnosis between Crohn's disease and ulcerative colitis.     

Neutrophil signaling alteration: an adverse inflammatory response after burn shock

BACKGROUND: Perinuclear antineutrophil cytoplasmic antibodies occur frequently in adult patients with chronic pouchitis after colectomy and ileal pouch-anal anastomosis for ulcerative colitis. The purpose of the study was to determine the prevalence of perinuclear antineutrophil cytoplasmic antibodies and cytoplasmic antineutrophil cytoplasmic antibody in children and adolescents who undergo colectomy and ileal pouch-anal anastomosis for ulcerative colitis and familial adenomatous polyposis. METHODS: Five groups of children and adolescents (age, <20 years) were studied, with the following histories: acute pouchitis and history of ulcerative colitis; chronic pouchitis and history of ulcerative colitis; pouchitis with Crohn's disease features and a history of ulcerative colitis; no pouchitis and a history of ulcerative colitis; and familial adenomatous polyposis, with or without pouchitis. Antineutrophil cytoplasmic antibody levels and titers were detected in postoperative sera by enzyme-linked immunosorbent assay, and positive results were subtyped by indirect immunofluorescence. RESULTS: The frequency of perinuclear antineutrophil cytoplasmic antibodies and cytoplasmic antineutrophil cytoplasmic antibody in patients with a history of ulcerative colitis were 67% and 15%, compared with a 0% presence in patients with familial adenomatous polyposis (p < 0.001). There was no significant correlation between the frequency of perinuclear antineutrophil cytoplasmic antibodies and ulcerative colitis patient subgroups (patients with and without pouchitis, 66% and 75%). Similarly, there was no significant correlation between the frequency of cytoplasmic antineutrophil cytoplasmic antibodies among ulcerative colitis patient subgroups (patients with and without pouchitis, 19% and 8%). The frequency of cytoplasmic antineutrophil cytoplasmic antibody in patients with Crohn's disease features (50%), was increased, but this difference was not significant. CONCLUSIONS: There is a high frequency of perinuclear antineutrophil cytoplasmic antibodies in children and adolescents who undergo ileal pouch-anal anastomosis for ulcerative colitis, whether or not they have pouchitis. The frequency of cytoplasmic antineutrophil cytoplasmic antibody is lower in this patient population. Additional studies will be required to determine whether the presence of cytoplasmic antineutrophil cytoplasmic antibody is associated with the postoperative development of features of Crohn's disease.