The role of vitamin therapy in chronic ulcerative colitis; a case report.
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Colitis↗
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Misplaced epithelium in ulcerative colitis and Crohn's disease of the colon and its relationship to malignant mucosal changes.
The presence of misplaced mucosal epithelium was studied in the colectomy specimens from 30 patients with Crohn's disease, 30 patients with ulcerative colitis, 15 patients with ulcerative colitis complicated by carcinoma and 30 patients with non-colitic colorectal carcinoma. Misplaced epithelium was present in 21 (70%) of the resection specimens with Crohn's disease, 20 (66.7%) with ulcerative colitis and 12 (80%) with ulcerative colitis complicated by carcinoma. None of the specimens with non-colitic colorectal adenocarcinoma showed misplaced foci of epithelium. Two pathogenetic mechanisms for epithelial misplacement are proposed: (1) the effects of mucosal inflammation and repair; and (2) muscular abnormalities in inflammatory bowel disease. The proposed mechanisms and patterns of epithelial misplacement are discussed and illustrated. The importance of its recognition is emphasized because, when associated with mucosal dysplasia, difficulties in interpretation arise in distinguishing it from 'early' invasive adenocarcinoma. Epithelial misplacement is common in patients with longstanding ulcerative colitis and may be a factor in increasing the significance of pre-existing mucosal dysplasia and promoting the development of adenocarcinoma. This may explain the unusual growth pattern encountered in ulcerative colitis, of submucosal cancer underlying a flat, non-dysplastic mucosa.
Adenocarcinoma↗
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↗
Cyclosporin for severe ulcerative colitis.
BACKGROUND: About one-third of patients with severe ulcerative colitis do not respond to conventional therapy and require urgent colectomy. It was recently shown that cyclosporin is effective in some of these patients. OBJECTIVES: To review the current experience of six hospitals in central Israel that used cyclosporin in patients with severe ulcerative colitis. METHODS: The files of all 32 patients treated with cyclosporin for corticosteroid-resistant ulcerative colitis were reviewed. Activity of disease was measured by a clinical activity, index colonoscopy and laboratory tests. RESULTS: The average duration of treatment with intravenous cyclosporin was 12.7 days (range 9-28) after which the disease activity index dropped from an average of 14.22 to 4.74. The mean time for response was 7.5 days (4-14). Twelve patients (40%) required surgery within 6 months and another 6 patients (18.8%) were operated on after more than 6 months. Twelve patients (37%) maintained remission for at least 6 months and did not require surgery. In one patient treatment was stopped because of non-compliance and one was lost to follow-up. There were numerous side effects, but in only one case with neurotoxicity was treatment withdrawn. CONCLUSIONS: Cyclosporin is a relatively safe and effective treatment for severe ulcerative colitis. It induced long-term remission in 37% of the patients, and in those who required surgery the treatment resulted in an improved clinical condition before the operation.
Adolescent↗
Cellular immune reactions against common antigen, small intestine, and colon antigen in patients with Crohn's disease, ulcerative colitis, and cirrhosis of the liver.
Patients with ulcerative colitis showed in 71-93%, patients with cirrhosis of the liver in 64-91%, cellular immunity against Common Antigen (CA) and human fetal intestinal antigens as measured by the leucocyte migration test (LMIT). Patients with Crohn's disease exhibited cellular immune reactions to a lesser degree - from these only patients without immunosuppressive therapy differed significantly from normal controls (p less than 0.05). Approximately 30% of patients with Crohn's disease and ulcerative colitis had elevated antibody titers against intestinal antigens and CA. A high percentage of patients in both diseases showed a reciprocal relationship between cellular and humoral immunity. It was concluded that Crohn's disease and ulcerative colitis can be separated in most cases using intestinal antigens and CA in the LMIT. The occurrence of cellular immunity against these antigens cannot be interpreted as being the only pathogenetic principle in these two diseases. It is also concluded that there appears to be only a weak immune tolerance against intestinal antigens. The high percentage of cellular immune reactions in patients with cirrhosis of the liver demonstrates that this group may have an impairment of the physiological elimination of antigens by the liver.
Antibodies↗
Milk tolerance in adults with ulcerative colitis.
OBJECTIVES: There has been concern in the literature and among physicians and patients that milk intolerance may contribute to disease activity in ulcerative colitis. We sought to define whether patients with ulcerative colitis have problems with milk tolerance. METHODS: 1) A questionnaire was administered to a group of gastroenterologists. 2) Consecutive unselected ulcerative colitis patients were administered a questionnaire regarding issues concerning their ingestion and tolerance of milk products. 3) Patients, and age- and ethnically matched controls, underwent lactose hydrogen breath testing at a 50-g dose, and if intolerant, returned for testing at a 12.5-g dose. RESULTS: Eighty percent of responding physicians stated that they recommend avoidance of milk products at some time to their patients. Thirteen of 29 (44%) ulcerative colitis patients were lactose intolerant compared with five of 14 (36%) controls (p = 0.57). Of 11 subjects returning for the 12.5-g test dose, only three (28%) were intolerant. Of 10 ulcerative colitis patients tested during a flare, only two (20%) were intolerant. Nineteen of 28 (66%) patients reduced or eliminated milk products from their diet, but only 10 (45%) of these patients were lactose intolerant. The discordance rate for predicting lactose tolerance status among patients was 35%. By logistic regression analysis, age (p = 0.04) and ethnicity (p = 0.006) were the only variables that were predictive of an abnormal lactose hydrogen breath test. CONCLUSIONS: There are common misperceptions among physicians and patients about lactose intolerance in ulcerative colitis. Lactose intolerance in patients with ulcerative colitis is dependent on their age and ethnicity and not any particular aspects of their disease. The proscription of milk products during flares of disease by many physicians is not supported by this study.
Adult↗
Turnbull-Blowhole colostomy for toxic ulcerative colitis in pregnancy: report of two cases.
PURPOSE: Surgical intervention for toxic ulcerative colitis in pregnancy is associated with a high morbidity and mortality for both mother and her fetus. A limited surgical procedure may be desirable to reduce the risk of maternal and fetal mortality. We describe the use of "blowhole" colostomy and loop ileostomy (Turnbull procedure) in the management of toxic dilation of the colon complicating ulcerative colitis in pregnancy. METHODS: The medical records of two pregnant females with toxic ulcerative colitis were reviewed. The presentations, management, and outcomes of these patients and their neonates are described. RESULTS: The Turnbull-Blowhole colostomy and ileostomy was used in the acute management of toxic ulcerative colitis in two pregnant females. Both mothers and neonates had successful outcomes with resolution of the acute process. Completion proctocolectomy and ileal pouch-anal anastomosis was later performed in both patients. CONCLUSIONS: The colonic decompression and fecal diversion procedure provided minimal operative trauma to the mother and fetus and resulted in successful outcome in the management of toxic ulcerative colitis in pregnancy. We believe the procedure is safe, effective, and relatively simple, which may reduce the morbidity and mortality of toxic colitis in pregnancy.
Adult↗
Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis.
BACKGROUND: Aminosalicylates are used as standard treatment for maintaining remission in ulcerative colitis. As yet, there is no other existing alternative with proven efficacy. In light of the hypothesis that the intestinal environment may contribute to the pathophysiology of ulcerative colitis, a trial was conducted to test the effects of probiotic treatment with an oral preparation of non-pathogenic E. coli. METHODS: A total of 120 patients with inactive ulcerative colitis were included in a double-blind, double-dummy study comparing mesalazine 500 mg t.d.s. to an oral preparation of viable E. coli strain Nissle (Serotype 06: K5: H1) for 12 weeks with regard to their efficacy in preventing a relapse of the disease. Study objectives were to assess the equivalence of the clinical activity index (CAI) under the two treatment modalities and to compare relapse rates, relapse-free times and global assessment. RESULTS: The start and end scores of the CAI demonstrated no significant difference (P = 0.12) between the two treatment groups. Relapse rates were 11.3% under mesalazine and 16.0% under E. coli Nissle 1917 (N.S.). Life table analysis showed a relapse-free time of 103 +/- 4 days for mesalazine and 106 +/- 5 days for E. coli Nissle 1917 (N.S.). Global assessment was similar for both groups. Tolerability to the treatment was excellent and did not differ. No serious adverse events were reported. CONCLUSIONS: From the results of this preliminary study, probiotic treatment appears to offer another option for maintenance therapy of ulcerative colitis. Additional support is provided for the hypothesis of a pathophysiological role for the intestinal environment in ulcerative colitis.
Adult↗
Pulmonary vasculitis complicating childhood ulcerative colitis.
A case of pulmonary vasculitis complicating ulcerative colitis is presented, and the literature is reviewed. Unexplained pulmonary problems complicating severe ulcerative colitis should prompt a review of rare etiologies to include pulmonary vasculitis, apical pulmonary fibrosis, and salicylazosulfapyridine-induced lung disease. Lung biopsy will establish a diagnosis of pulmonary vasculitis.
Age Factors↗
Antibodies to neutrophil cytoplasma in patients with ulcerative colitis and their first-degree relatives in Thailand.
BACKGROUND: The prevalence of perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) does not significantly vary in ethnically diverse populations. The prevalence of p-ANCA is high in ulcerative colitis and primary sclerosing cholangitis. While the prevalence of ulcerative colitis in Asian populations is low, it is interesting to know the prevalence of p-ANCA in such a population. METHODS: Sera from 33 cases of ulcerative colitis diagnosed during the last 10 years at the diarrhea clinic, Division of Gastroenterology, Siriraj Hospital, were prospectively compared with case controls consisting of 15 cases of diarrhea from non-inflammatory bowel diseases and 25 non-diarrheic patients. Indirect immunofluorescence assay was used to detect p-ANCA in all the sera. RESULTS: Positive p-ANCA tests were found in 13 of the 33 patients with ulcerative colitis and in one of the 40 controls. Sensitivity of the test was 39.4% and the specificity was 97.5%. The one patient with positive p-ANCA in the control group was the patient with irritable bowel syndrome. Of the 13 p-ANCA-positive ulcerative colitis patients, two cases were found to have proctosigmoiditis, seven cases had left-sided colitis, and four cases had pancolitis. Perinuclear antineutrophil cytoplasmic antibodies was one of the 22 cases of first-degree relatives of ulcerative colitis patients (22 relatives from 12 index ulcerative colitis cases). There was no correlation between the positivity of p-ANCA and disease activity, and extent of the disease. CONCLUSION: The prevalence of p-ANCA in Thai patients with ulcerative colitis (39.4%) is lower than that in the Western population. Although the prevalence of p-ANCA is low in the Thai population, it should serve as a useful tool in diagnosing ulcerative colitis in this part of the world where the disease is uncommon and difficult to diagnose. The negativity of p-ANCA in almost all first-degree relatives of Thai ulcerative colitis patients should be further elucidated.
Adult↗
Expression profiling of apoptosis-related genes in enterocytes isolated from patients with ulcerative colitis.
Apoptosis regulation has been implicated as a main cause of epithelial dysfunction in patients with ulcerative colitis. Apoptosis can be divided into distinct pathways, which depend on the expression of a large number of apoptosis-related genes. The aim was to elucidate which pathways are dominant in normal and inflamed colonic epithelial cells. An apoptosis-specific gene array expression profiling system of 96 genes was used to determine the expression profile of apoptosis-related genes. Epithelial cells isolated from three patients with active ulcerative colitis were pooled and compared to pooled epithelial cells isolated from three control subjects. Genes found to be three-fold or more overexpressed in ulcerative colitis were subsequently analysed by PCR in a larger population (10 patients with ulcerative colitis, 8 control subjects). Selected genes found not to be regulated were additionally tested by PCR in the same population. Six genes were found to be highly expressed in epithelial cells from both controls and ulcerative colitis patients. These included Bcl-2 antagonist/killer, B lymphoid tyrosine kinase, caspase 14, Harakiri, tumour necrosis factor (TNF) receptor 2, and TNF receptor-associated factor 1 (TRAF1). Three genes were found to be upregulated in ulcerative colitis (p<0.01): caspase 1 and 5, and inhibitor of apoptosis protein 2 (c-IAP2). Both receptor- and mitochondrion-dependent apoptosis pathways are well expressed in enterocytes. Mainly activation-dependent and cytoprotective genes were upregulated in ulcerative colitis.
Adolescent↗
Verapamil inhibits in-vitro leucotriene B4 release by rectal mucosa in active ulcerative colitis.
Increased mucosal eicosanoid synthesis occurs in active ulcerative colitis; suppression of the synthesis of pro-inflammatory leucotrienes could be therapeutically useful. Neutrophil 5-lipoxygenase is calcium-dependent. In this study, the effect of the calcium channel antagonist, verapamil, on the release of eicosanoids by colitic rectal mucosal biopsies has been examined. Verapamil in therapeutic concentration (5 micrograms/ml, 10(-5) M) reduced leucotriene B4 release from actively inflamed rectal mucosa by 30% (from 60 (5.0 S.E.M.) ng/g wet weight/20 min without, to 42 (5.7 S.E.M.) with verapamil, P less than 0.05), but had no effect on leucotriene B4 release by rectal biopsies taken from patients with quiescent ulcerative colitis (39 (2.8 S.E.M.) ng/g wet weight/20 min without, and 43 (5.0 S.E.M.) with verapamil). Verapamil did not affect mucosal prostaglandin E2 release. The results suggest that, in active ulcerative colitis, verapamil inhibits mucosal 5-lipoxygenase activity and warrants therapeutic evaluation.
Biopsy↗
[Investigations on the ultrastructural pathology of the ulcerative colitis (author's transl)].
The ultrastructural pathology of ulcerative colitis was investigated on a group of 37 colitis patients. Among the epithelial changes, the alterations of the microvilli and of the glycocalyx of the surface epithelium are quite evident. These alterations may possibly be understood as a morphological substrate of a partly impaired "mucosa block" of the surface epithelium (IgA- and "secretory piece" deficiency). Hypothetically, this partly impaired "mucosa block" is considered to be an essential pathogenetic moment of ulcerative colitis. The inflammatory infiltrate of the stratum proprium mucosae is characterized in particular by numerous lymphocytes, plasma cells and macrophages. The close topographical interrelation of these cells observed here seems to indicate a functional cooperation in the auto-immunological process, as it is discussed here in connection with ulcerative colitis.
Adult↗
Cytology and image cytometry after colonic lavage: a complementary diagnostic tool in patients with ulcerative colitis.
BACKGROUND: Patients with extensive, long-standing ulcerative colitis have increased risk of colorectal cancer. AIMS: To improve the detection of high-risk patients, using a combination of colonic cytology, histology, and DNA image cytometry after segmental colonic lavage. PATIENTS: A series of 16 patients (8 high-risk patients) with ulcerative colitis were investigated. METHODS: After segmental lavage step, biopsies were obtained. Gradient centrifugation of the colonic fluid was performed for isolation and purification of epithelial cells. The smears and biopsy specimens obtained were stained for routine interpretation and for DNA image cytometry. RESULTS: Segmental lavage could be performed in all patients. Specimens from two high-risk patients showed low grade dysplasia and atypia by means of histology and cytology, respectively. In one patient, without increased colorectal cancer risk, atypia was detected. Three patients in the high-risk group, two of those diagnosed as positive for dysplasia and atypia, showed aneuploidy histologically and cytologically. DNA aneuploidy, in cytological material, was found exclusively in three low-risk patients, one of those had atypia cytologically. CONCLUSIONS: Isolation and purification of epithelial cells after segmental colonic lavage using density gradient centrifugation can be performed as part of routine endoscopy. It provides information about atypical cells and DNA aneuploidy as additional markers of malignant transformation. The combination of cytologic examination and DNA image cytometry might improve the detection of high-risk ulcerative colitis patients.
Adult↗
[Surgical treatment of unspecific chronic ulcerative colitis. A 5-year experience].
BACKGROUND: Treatment of ulcerative colitis depends on clinical stage of disease and have precise surgical indications. The aim of this work was to review surgical indications and present data related to our experience. MATERIAL AND METHODS: Retrospective, descriptive, and transversal study. We reviewed records of all patients who underwent a surgical procedure for ulcerative colitis at our service from March 1996 to March 2001. RESULTS: Twenty two patients, 13 males and nine females, ages range 21 to 72 years. Main indication for surgery was no response to medical treatment (50%). Surgical procedures was subtotal colectomy with ileostomy in one patient, intersphincteric proctocolectomy with ileostomy in four intersphincteric proctectomy with ileostomy in three ileorectalanastomosis in three proctocolectomy with ileoanal "J" pouch in six and proctectomy with ileoanal J pouch in five. We had the following complications: oral candidiasis; phlebitis; eventration; pouchitis, and anal fissure in one patient, respectively, pouch-skin fistula in two patients (9%), and retrograde ejaculation in one of these. Follow-up was for 5 years. CONCLUSIONS: Surgical indications for ulcerative colitis are precise. We recommend early surgical evaluation. Ileoanal pouch is now considered the gold standard for surgical procedure because it eliminates disease, neoplasm development, and permanent extra-colonic manifestations, and restores continence.
Adult↗
Atrophy and neoplastic transformation of the ileal pouch mucosa in patients with ulcerative colitis and primary sclerosing cholangitis: a case control study.
INTRODUCTION: Patients with ulcerative colitis and primary sclerosing cholangitis have an increased risk of developing carcinoma both in the bile ducts and in the colon. PURPOSE: To investigate whether this patient group also has an increased risk of developing atrophy and neoplasia in the ileal pouch mucosa after construction of a pelvic pouch with an ileoanal anastomosis or a continent Kock ileostomy. METHODS: Flexible video endoscopic examinations of the ileal pouch were performed in 16 patients with ulcerative colitis and primary sclerosing cholangitis and in 16 matched patients with ulcerative colitis without sclerosing cholangitis. Biopsies were sampled from different locations in the pouch for histologic assessment of mucosal atrophy and dysplasia and for flow cytometric DNA analysis assessing chromosomal aberrations. RESULTS: The patients with sclerosing cholangitis developed moderate or severe atrophy in the pouch significantly more often (P < 0.01). Persistent severe mucosal atrophy was revealed in eight patients with sclerosing cholangitis and only in two controls. One patient with sclerosing cholangitis had high-grade dysplasia in multiple locations. Low-grade dysplasia was assessed in three patients with sclerosing cholangitis and in two of the controls. DNA aneuploidy was displayed in three patients, all with sclerosing cholangitis and dysplasia. All patients with neoplastic transformation had a pouch with ileoanal anastomosis and a long pouch duration (> 8 years). CONCLUSION: Patients with ulcerative colitis and primary sclerosing cholangitis with an ileal reservoir are more prone to developing mucosal atrophy in the pouch and seem to have a higher risk of neoplastic transformation in the pouch mucosa than patients with ulcerative colitis without sclerosing cholangitis.
Adult↗
Pain and mechanical properties of the rectum in patients with active ulcerative colitis.
BACKGROUND: The pain, urgency, and incontinence in ulcerative colitis may be related to changes in viscoelastic properties of the gut wall or to alterations of the sensory pathways. In the present study, we used an advanced rectal probe to study the mechanosensory and smooth muscle properties in patients with active disease. METHODS: Nine patients with ulcerative colitis (mean age 39.5 years) with exacerbation limited to the rectum and sigmoid colon and 17 age-matched healthy subjects were included. The rectum was distended before and after pharmacological relaxation of the smooth muscle until moderate pain was reported, and the cross-sectional area, volume, pressure, tension, and strain were computed. To investigate central integration of a tonic stimulus, the bag was finally distended to the pain threshold; then, the cross-sectional area was held constant for 2 min. RESULTS: The patients were hypersensitive to mechanical stimuli as assessed by the cross-sectional area (F = 21.7; P < 0.001). There were no differences in compliance or stiffness between the 2 groups, but the hypersensitivity was abolished after muscle relaxation. Together with the muscle analysis, this finding demonstrated that the smooth muscles were tonically contracted in the inflamed rectum, resulting in a decreased rectal circumference. The tonic distensions did not evoke central integration of the pain response, indicating that hyperalgesia is more likely related to peripheral factors. CONCLUSIONS: Patients with active ulcerative colitis have hypersensitivity and increased tone of the smooth muscles, which may explain the symptoms. Drugs that affect smooth muscle contraction may be helpful in difficult cases.
Adult↗
Anti-neutrophil cytoplasmic antibodies in ulcerative colitis. Comparison with other colitides/diarrheal illnesses.
Previous studies from this laboratory showed that serum anti-neutrophil cytoplasmic antibodies, distinct from those associated with active Wegener's granulomatosis, are present in the majority of patients with ulcerative colitis. In this study, the specificity of anti-neutrophil cytoplasmic antibodies for ulcerative colitis as compared with other colitides and diarrheal illness was determined. In a blinded study, test samples of serum were screened for anti-neutrophil immunoglobulin G in a fixed neutrophil enzyme-linked immunosorbent assay. Levels of neutrophil binding by immunoglobulin G and titers of anti-neutrophil immunoglobulin G in sera from patients with ulcerative colitis and patients with ulcerative colitis post colectomy were each significantly greater than the levels and titers for normal controls and patients with a variety of other colitides and diarrheal illnesses. Levels of neutrophil binding for colonic Crohn's disease, bacterial/amoebic colitis, the irritable bowel syndrome with diarrhea, and other miscellaneous diarrheal illnesses were not significantly different than the levels for normal controls. Although the levels of binding for collagenous colitis were significantly less than the levels for ulcerative colitis, they were significantly greater than the levels for normal controls. Patterns of neutrophil binding by serum samples that were positive in the enzyme-linked immunosorbent assay were determined by indirect immunofluorescence. Perinuclear staining was the predominant pattern shown by sera from patients with ulcerative colitis. The combination of a positive value in the enzyme-linked immunosorbent assay and a perinuclear immunofluorescence pattern was 60% sensitive and 94% specific for ulcerative colitis. It is concluded that anti-neutrophil cytoplasmic antibodies in ulcerative colitis are not simply an epiphenomenon related to inflammation of the colon. Identification of the antigen(s) to which these autoantibodies are directed may facilitate understanding of the underlying immune response and may allow development of an assay that is more sensitive and specific for ulcerative colitis.
Adult↗