Ferritin in Crohn's disease tissue: detection by electron microscopy.

Using immune electron microscopy, an attempt has been made to visualise viral particles in Crohn's disease tissue and faeces. No particles resembling viruses were observed, but in the absence of a specific antiserum a negative result does not exclude the presence of a virus, particularly if it is sparsely distributed. Compared with controls, an abundance of a 12 nm particle was found in all Crohn's disease tissue and one small intestinal lymphoma. This particle has been identified as ferritin and is unlikely to be of aetiological significance.     

Scanning electron microscopy of rectal mucosa in Crohn's disease

Rectal biopsies from healthy control subjects, and from patients with Crohn's disease whose rectal mucosa appeared normal by sigmoidoscopy and light microscopy, were examined by scanning electron microscopy. Appearances within both groups were quite variable, and no clear differences between the groups could be distinguished.     

Minute findings by magnifying colonoscopy are useful for the evaluation of ulcerative colitis

BACKGROUND: Colonoscopy has an important role in the diagnosis of ulcerative colitis. However, colonoscopic findings are inadequate for the prediction of relapse without histologic examination. In this study, the role of magnifying colonoscopy in ulcerative colitis was evaluated. METHODS: One hundred sixteen magnifying colonoscopy observations were made in 61 patients with ulcerative colitis between January 1994 and October 1998. A simple classification of magnifying colonoscopic findings into 5 categories was devised as follows: regularly arranged crypt openings, villous-like, minute defects of epithelium, small yellowish spots, and coral reef-like appearance. The colonoscopic findings by classification were compared with histopathologic findings, and the usefulness of the classification for predicting relapse was prospectively analyzed in 18 patients. RESULTS: Compared with grade as determined by conventional colonoscopy, there was a better correlation between the classification of findings by magnifying colonoscopy and histopathologic findings (r(2) = 0.665, 0.807, respectively). Of 18 patients studied prospectively, 7 of 9 with minute defects of epithelium relapsed within 6 months, and the cumulative nonrelapsing rate was significantly lower in patients with minute defects of epithelium compared with those without minute defects of epithelium (p = 0.0059). Moreover, minute defects of epithelium was found to be a significant independent predictive factor for relapse (multivariate analysis, Cox proportional hazards model; p = 0.0203). CONCLUSIONS: Our proposed classification of magnifying colonoscopic findings in patients with ulcerative colitis is useful for the evaluation of disease activity and for the prediction of periods of remission.     

Clinical course and magnifying endoscopic findings of fine lesions of the large intestinal mucosa in Crohn's disease

"Worm-eaten" appearance (WEA) is a fine lesion of Crohn's disease observed in apparently normal rectal mucosa by magnifying endoscopy. Magnifying endoscopy has now been performed following application of methylene blue on 37 occasions in 27 patients with Crohn's disease, and the occurrence of WEA was reviewed in relation to the duration and extent of disease. The frequency of WEA was 75% in patients with a history of less than five years and 77% in those who had had the disease for more than five years. In the active stage, the frequency was 85% and 100% respectively, and the degree of WEA also increased. The detection rate of granulomata in regions of WEA was 53% when the clinical history was less than five years and 33% when five years or more. In active disease, granulomata were found in 70% and 67% respectively. The large intestine other than the rectum was reviewed in eight patients with ileitis. WEA and granulomata were observed throughout the large intestine including the cecum, especially when the ileal disease was active.     

The small-intestinal mucosa in patients with Crohn's disease assessed by scanning electron and light microscopy

Small-intestinal mucosal biopsy specimens obtained by a Watson capsule were assessed by light (LM) and scanning electron (SEM) microscopy in 18 patients with various sites of Crohn's disease and in 6 healthy controls. By means of LM, partial villous atrophy of the upper small-intestinal mucosa was assessed in six patients. With the use of SEM a further seven patients were shown to have mucosal abnormalities of possible clinical significance. These specimens showed a convoluted villous pattern at low-power SEM and some also enterocyte irregularity, bulging, and surface ultrastructural distortion at medium- and high-power SEM. The medium- and high-power mucosal alterations were unevenly distributed. The high prevalence of abnormalities of the upper small-intestinal mucosa in patients with Crohn's disease elsewhere in the gastrointestinal tract adds further weight to the concept of a diffuse involvement along the entire gastrointestinal tract in Crohn's disease.     

Expression of adhesion molecules and HLA-DR by macrophages and dendritic cells in aphthoid lesions of Crohn's disease: An immunocytochemical study

The phenotypes and ultrastructure of macrophages and dendritic cells in aphthoid lesions of the colon were immunocytochemically observed in patients with Crohn's disease. Biopsy specimens were endoscopically obtained from both aphthoid and advanced lesions in Crohn's disease patients. Biopsy specimens obtained from patients with infectious colitis and from normal individuals served as controls. Aphthoid lesions contained densely aggregated CD68⁺ macrophages, which were surrounded by numerous ID-1⁺ dendritic cells. In the normal controls and infectious colitis patients, however, a few scattered CD68⁺ macrophages and ID-1⁺ dendritic cells were noted beneath the surface epithelium. CD3⁺ lymphocytes were significantly increased in both aphthoid and advanced lesions of Crohn's disease, but the CD4/CD8 ratio was similar in all groups studied. The double immunoperoxidase staining method revealed that both CD68⁺ macrophages and ID-1⁺ dendritic cells in the aphthoid lesions simultaneously expressed ICAM-1 and HLA-DR antigens. Electronmicroscopic observation revealed that CD68⁺ macrophages had numerous vesicles and lysosomal granules and few projections, and that ID-1⁺ dendritic cells had appreciable cytoplasmic protrusions with a few vacuoles. These findings suggested that the colonic mucosa in Crohn's disease contained two types of macrophage/dendritic cells in the same lineage that expressed intercellular adhesion molecules and class-II MHC antigens. It also appeared that the aphthoid lesions of Crohn's disease featured an increase in macrophages and dendritic cells consistent with immunological activation. Part of this work was presented at the symposium of the 78th Annual Meeting (April, 1992, Tokyo, Japan) and the research forum of the 79th Annual Meeting (March 1993, Kyoto, Japan) of the Japanese Society of Gastroenterology.     

克罗恩病的发病机制和治疗进展

克罗恩病（Crohn＇s disease,CD）是一种以小肠为主,累及全层节段性全胃肠道的非特异性炎症性肠道疾病（inflammatory bowel disease,IBD）。该病须与溃疡性结肠炎、急性感染性结肠炎等鉴别诊断。该病存亚洲的发病率远低于西方国家,近10年来在我国的发病率有明显上升趋势。CD的病因与发病机制尚不明确,临床表现也复杂多样,且容易误诊,复发率高。在过去的10多年里,遗传和肠道免疫领域取得的研究成果为我们在研究IBD病因以及治疗上提供了新的思路。本文就CD的发病机制和治疗进展作一综述。     

Pathogenesis of gall stones in Crohn's disease: an alternative explanation.

The increased prevalence of gall stones in Crohn's disease is thought to be related to depletion of the bile salt pool due either to terminal ileal disease or after ileal resection. This study was designed to examine whether this hypothesis is correct and explore alternative explanations. Two hundred and fifty one randomly selected patients (156 females, 95 males, mean age 45 years) were interviewed and screened by ultrasonography to determine the prevalence of gall stones in a large population of patients with Crohn's disease. Sixty nine (28%) patients had gall stones proved by ultrasonography (n = 42), or had had cholecystectomy for gall stone disease (n = 27). The risk factors for the development of gall stones including sex, age, site, and duration of disease, and previous intestinal resection were examined by multivariate analysis. Age and duration of disease were positive risk factors for gall stones and were covariables. The site of disease and of previous intestinal resection did not predispose to gall stones. Previous surgery was an independent risk factor for the development of gall stones, the risk increasing with number of laparotomies. It is suggested that mechanisms other than ileal dysfunction may predispose to gall stones. Postoperative gall bladder hypomotility with biliary sludge formation may be precursors of gall stone formation in patients with Crohn's disease.     

Pathogenesis of postoperative recurrence in Crohn's disease

The majority of patients with Crohn's disease (CD) require surgery during the course of their disease, but such surgery is typically not curative. Although some studies suggest that the disease state is theoretically reset to its earliest phase following surgery, disease phenotype and natural history of CD do not change significantly after surgery, leading to high rates of recurrence. Factors predisposing to this recurrence are not well defined, so there is a need for and a unique opportunity to develop a better understanding of the pathogenesis of recurrent inflammation and associated risk factors after an ileocolic resection. This paper reviews the postoperative disease outcome and evolution based on defining the combination of the patient's microbial flora, environmental exposure history, immune response and genetic make-up.     

克罗恩病肠道纤维化的发生机制和临床治疗

肠道纤维化是克罗恩病的特征表现,其反复发作导致的肠道狭窄是克罗恩病最严重的并发症之一,目前治疗手段有限.本文对克罗恩病肠道纤维化发生机制及目前治疗手段进行综述.     

Crohn's disease activity assessed by fecal calprotectin and lactoferrin: correlation with Crohn's disease activity index and endoscopic findings

BACKGROUND: Correlation of endoscopic Crohn's disease activity with fecal calprotectin and lactoferrin is insufficiently studied. We evaluated the clinical significance of these neutrofil-derived proteins in assessment of Crohn's disease activity by comparing them with endoscopic disease activity and with Crohn's disease activity index (CDAI) and serum CRP. METHODS: A total of 77 CD patients underwent one or more ileocolonoscopies (n = 106) with scoring of Crohn's disease index of severity (CDEIS). Patients provided stool samples for calprotectin and lactoferrin measurements and blood samples for CRP. Clinical activity was based on the CDAI. RESULTS: Both fecal calprotectin and lactoferrin correlated significantly with CDEIS (Spearman's r 0.729 and 0.773, P < 0.001). With a cutoff level of 200 microg/g for a raised fecal calprotectin concentration, sensitivity was 70%, specificity 92%, positive predictive value (PPV) 94%, and negative predictive value (NPV) 61% in predicting endoscopically active disease (CDEIS >/= 3). A fecal lactoferrin concentration of 10 microg/g as the cutoff value gave a sensitivity, specificity, PPV, and NPV of 66%, 92%, 94%, and 59%. Sensitivity of CDAI >/= 150 to detect endoscopically active disease was only 27%, specificity 94%, PPV 91%, and NPV 40%. A raised serum CRP (> 5 mg/l) gave a sensitivity, specificity, PPV, and NPV of 48%, 91%, 91%, and 48%.Conclusions: For evaluation of Crohn's disease activity, based on endoscopic findings, more sensitive surrogate markers than is CDAI or CRP are fecal calprotectin and lactoferrin. These prove to be useful tools for estimation of disease activity in Crohn's disease.     

Surgical management of ileosigmoid fistulas in Crohn's disease: Role of preoperative colonoscopy

PURPOSE: Surgical treatment of ileosigmoid fistulas in Crohn's disease remains controversial and can be radical (resection of both segments) or conservative (ileal resection with suture or wedge resection of the sigmoid). At our institution, the sigmoid defect is sutured if the sigmoid is not affected by primary Crohn's disease or by important stricture; otherwise, the sigmoid is resected. We reviewed our experience to evaluate our results with this procedure. METHODS: Thirty patients with ileosigmoid fistulas underwent operation. Among them, 15 had a preoperative colonoscopy, whereas others had no Endoscopic work-up. In nine patients, the sigmoid was thought to be affected by Crohn's disease (n = 7) or stricture (n = 2) and was resected. In 21 patients, the sigmoid was thought to be affected by proximity, and a simple suture (n = 15) or wedge resection (n = 6) was performed. Eleven patients had a temporary stoma (37 percent). One had coloproctectomy. RESULTS: One patient died postoperatively. One patient had postoperative sigmoidocutaneous fistula after conservative treatment. Histology of the sigmoid specimen showed Crohn's disease in 8 patients (27 percent), including 5 of 9 resected specimens, and 3 of 21 conservative procedures. All patients with Crohn's misdiagnosis did not have preoperative colonoscopy. Nine of 11 stomas were closed in a median delay of four months. With a median delay of nine years, four patients have again undergone surgery for recurrent colonic Crohn's disease, all of whom underwent surgery initially without preoperative colonoscopy. CONCLUSION: Preoperative Endoscopic assessment of the colon is a reliable guide to use when choosing between sigmoid resection or a conservative approach and can result in reduced morbidity and improved long-term results.     

Campylobacter pyloridis in peptic ulcer disease: microbiology, pathology, and scanning electron microscopy.

After the recent successful isolation of spiral organisms from the stomach this paper presents the bacteriological and pathological correlation of gastric antral biopsies from 51 patients endoscopied for upper gastrointestinal symptoms. Campylobacter pyloridis was cultured from 29 patients and seen by either silver staining of the biopsy or scanning electron microscopy in an additional three. The organism was cultured from 23 of the 33 (69%) patients with peptic ulcer disease and from within this group 17 (80%) of the 21 patients with duodenal ulceration. It was cultured only once from the 12 normal biopsies in the series but from 27 of the 38 (71%) biopsies showing gastritis. C pyloridis was also cultured from five out of seven of the 14 endoscopically normal patients, who despite this had biopsy evidence of gastritis. It was the sole organism cultured from 65% of the positive biopsies and scanning electron microscopy invariably revealed it deep to the surface mucus layer. C pyloridis persisted in the three patients with duodenal ulcers after treatment and healing. The findings support the hypothesis that C pyloridis is aetiologically related to gastritis and peptic ulceration though its precise role still remains to be defined.     

Budesonide in Crohn's disease: findings of a compassionate-use program

BACKGROUND/AIMS: Budesonide controlled-release (CR) capsules are effective for inducing remission of Crohn's disease (CD) and are associated with fewer side effects than conventional corticosteroids. A compassionate-use program was implemented in countries where this treatment was unavailable. This paper reports the findings of this program. METHODOLOGY: Physicians were allowed to apply to AstraZeneca for a supply of budesonide CR capsules primarily for patients with CD who had experienced unacceptable side effects from conventional steroids or were unresponsive to other drugs. Physicians were requested to record adverse events (AEs) and patient response (1 = 'moderate'; 2 = 'well'; 3 = 'very well'). RESULTS: Four thousand and ninety-two patients were enrolled. There were 232 AE reports involving 326 different symptoms. There were 138 serious AEs (mainly gastrointestinal), and four deaths. Ten serious AEs were considered related to budesonide (no deaths). Budesonide was discontinued as a result of AEs in 147 patients (75 due to serious AEs, mainly gastrointestinal). Efficacy data were obtained from 1188 patients, with 943 (79%) responding 'well' or 'very well'. In the subgroups of patients that were young, elderly, or had unsuccessfully received immunosuppressants previously, the mean patient response score was >2. CONCLUSIONS: In a normal clinical setting, budesonide CR capsules were well tolerated by patients with ileocecal CD.     

Syphilitic posterior uveitis: correlative findings and significance.

Twenty-one patients with syphilitic posterior uveitis were investigated retrospectively to study the disease spectrum, associations with neurosyphilis, and therapeutic implications. Ophthalmologic manifestations of syphilitic posterior uveitis are differentiated into acute and chronic uveitides. The several distinct acute uveitic syndromes are usually florid and are associated with early syphilis, with VDRL-positive syphilitic meningitis, and frequently with human immunodeficiency virus coinfection. The chronic posterior uveitides are often insidious, a manifestation of late syphilis, and associated commonly with subclinical neurosyphilis. All patients with acute cases and 54% of patients with chronic cases in our study received penicillin therapy appropriate for neurosyphilis. The frequent association of syphilitic posterior uveitis with neurosyphilis and the analogous spirochetal sequestration beyond the blood-brain and the blood-ocular barriers suggest that all patients with syphilitic posterior uveitis, irrespective of ocular disease intensity, should undergo evaluation of cerebrospinal fluid and be treated with penicillin regimens appropriate for neurosyphilis.