Analysis of direct tissue isoelectric focused protein profiles of resected intestinal mucosa and endoscopic biopsies from patients with inflammatory bowel disease.

Direct tissue isoelectric focusing was used as a procedure to analyze differences in soluble tissue protein profiles of resected intestinal segments and endoscopic biopsies from patients with ulcerative colitis, Crohn's disease, and colonic cancer. Extraction of tissue proteins was accomplished by electrophoresis of mucosal cryostat sections on agarose gels across a broad pH gradient. The inflamed colonic mucosa from Crohn's disease patients showed similar isoelectric focusing protein patterns. Small bowel mucosa from a patient with both colonic diverticular disease and Crohn's disease showed protein patterns identical with that of the mucosa from a patient with only Crohn's disease. The inflamed mucosae from ulcerative colitis patients revealed identical protein patterns but were distinct from those of non-inflamed ulcerative colitis mucosa and from the inflamed mucosae from Crohn's disease patients. Non-inflamed small bowel mucosae from cancer, ulcerative colitis, and Crohn's disease patients showed distinct protein patterns which were absent in the non-inflamed large bowel mucosae. The inflamed resected ileum of a Crohn's disease patient exhibited protein patterns similar to those of the biopsy of an inflamed mid-transverse large bowel. Mucosal biopsies from inflamed sigmoid colon of a Crohn's disease patient showed different protein patterns than those in biopsies from the inflamed mid-transverse colon. Thus, distinctive isoelectric focusing protein patterns may be useful in differentiating Crohn's colitis and ulcerative colitis when granulomata are absent, and in resolving indeterminant colitis to one of these classic inflammatory bowel diseases.     

Small bowel magnetic resonance imaging for inflammatory bowel disease

The presented concept of hydro-magnetic resonance imaging (MRI) using a 2.5% mannitol solution as an orally applicable intraluminal contrast agent is a meaningful, reproducible, and reliable imaging method for the depiction of the small bowel. Especially in patients with Crohn's disease, hydro-MRI is the imaging method of first choice because hydro-MRI offers the advantage of a superior depiction of the inflamed bowel wall and the extramural complications of this disease without radiation exposure. In addition, hydro-MRI allows for a reliable assessment of the inflammatory activity, especially for the differentiation between an active and an inactive (scarred) stenosis. In particular, the mural enhancement, the length as well as the wall thickness of inflamed bowel segments, are considered to be significant MR parameters for the determination of the activity of Crohn's disease. Hydro-MRI of the colon is suitable for the depiction of pathologic changes in ulcerative colitis, but in contrast to Crohn's disease, the assessment of disease activity by hydro-MRI is unreliable in ulcerative colitis, probably because of the low spatial resolution (mucositis in ulcerative colitis vs. transmural inflammation in Crohn's disease). Hydro-MRI does not allow a reliable classification of inflammatory bowel diseases, but in ambiguous cases, hydro-MRI may provide helpful information for the differentiation of Crohn's disease and ulcerative colitis. There are no data of larger patient groups published regarding MR findings in inflammatory bowel diseases besides Crohn's disease and ulcerative colitis, but hydro-MRI is a promising imaging tool for these entities, which should be assessed in additional studies.     

Inflammatory bowel disease

Idiopathic inflammatory bowel disease consists of Crohn's disease and ulcerative colitis. Crohn's disease can affect any part of the gastrointestinal tract, from the mouth to the anus, and is also known as regional enteritis, terminal ileitis, or granulomatous colitis. Ulcerative colitis is limited to the colon and rectal involvement is present 95% of the time. Ten percent to fifteen percent of patients with irritable bowel syndrome cannot be clearly defined as having either Crohn's disease or ulcerative colitis and are termed indeterminate colitis.     

Crohn's disease and colorectal malignancy

There has been much debate over the past 50 years concerning the association between colorectal carcinoma and inflammatory bowel disease. Until recently, it was widely accepted there was a higher risk in those with widespread ulcerative colitis. However, evidence now suggests an almost equal incidence in those with Crohn's disease of similar extent and duration. We present a case that underlines the important clinical and pathological features of Crohn's disease associated colorectal carcinoma (CDAC). We present a literature review and debate the role of regular colonic surveillance in patients with Crohn's disease affecting the colon.     

Crohn's disease and ulcerative colitis. Evaluation with double-contrast barium examination and endoscopy

Double-contrast barium examination of the colon can demonstrate the changes associated with inflammatory bowel disease more completely and specifically than the single-contrast barium study. However, endoscopy is slightly more sensitive than double-contrast examination for detection of disease. In general, between 18% and 20% of patients with Crohn's disease or ulcerative colitis may be expected to have normal radiographic findings but endoscopically detectable disease. However, most false-negative double-contrast colon studies are associated with mild or minimal findings at proctosigmoidoscopy. Although double-contrast radiography may be less sensitive than endoscopy in detection of inflammatory bowel disease, it has similar accuracy for classification and differentiation. Most studies indicate an accuracy of 95% to 98% in differentiating Crohn's disease and ulcerative colitis, due to the fact that morphologic changes detected by the double-contrast mucosal study rarely overlap in the two diseases. Double-contrast barium examination and endoscopy are complementary studies, and the use of both may provide valuable information for evaluation of patients with suspected inflammatory bowel disease.     

Clinical features, morbidity and mortality of Scottish children with inflammatory bowel disease

From the Scottish Hospitals in-patients statistics for the years 1968-1983 all children and teenagers (a total of 1257) admitted to a National Health Service hospital with Crohn's disease or ulcerative colitis were identified. Case records of samples of patients with onset of symptoms at or before age 16 years were examined to establish the features, morbidity and mortality of unselected cohorts of young patients with inflammatory bowel disease. Median delay in diagnosis was less than six months. Anatomical distribution for Crohn's disease was similar to that in adults (small bowel 30 per cent; large bowel 28 per cent; small and large bowel 38 per cent) and almost half the patients with ulcerative colitis had extensive colitis. The morbidity was substantial in both. In-patient days for Crohn's disease ranged from seven to 322, median 64 days and for ulcerative colitis one to 275, median 30 days. At diagnosis, 11 of 40 young children with Crohn's disease but none of 14 with ulcerative colitis, were below the third centile for height. Despite treatment with corticosteroids 72 per cent of patients with Crohn's disease and 30 per cent of patients with ulcerative colitis required surgical treatment. Seventeen per cent have a permanent stoma. There were only six deaths, all before 1978.     

Autoimmunity, inflammatory bowel disease and hyposplenism.

The presence or absence of nine autoantibodies were assessed in 44 patients with ulcerative colitis (17 with hyposplenism) and 22 patients with Crohn's disease (eight with hyposplenism). The purpose of the study was to determine whether hyposplenism in inflammatory bowel disease is associated with an increased tendency to autoimmunity, or whether autoimmunity is linked not to hyposplenism itself but to the underlying bowel disease. The results strongly suggest that the latter hypothesis is correct. There was a much higher frequency of autoantibodies in patients with ulcerative colitis than in those with Crohn's disease (P < or = 0.01), suggesting that autoimmune factors are more important in the pathogenesis of ulcerative colitis than in Crohn's disease.     

Ultrasound findings in Crohn's disease and ulcerative colitis: a prospective study

In a prospective study, 118 patients with Crohn's disease, 51 patients with ulcerative colitis, and 72 patients with no disease of the intestine proximal to the rectum were evaluated by ultrasound. In Crohn's disease, thickening of the bowel wall and inflammatory masses were detected in 72.0% of the patients. With a transducer having optimal imaging properties in the near range, these findings were detected in 87.2% of a group of 47 patients. In ulcerative colitis, bowel wall thickening was detected in 52.9% of all patients. Thickening of the bowel wall was more marked in Crohn's disease than in ulcerative colitis. Most pathologic findings in Crohn's disease were located in the right lower abdomen, whereas those in ulcerative colitis were in the left abdomen, in particular in the lower quadrant. The frequency of wall thickening was correlated to the activity of the disease in ulcerative colitis but not in Crohn's disease. Considerably increased wall thickness, when localized in the right lower quadrant and found in combination with inflammatory masses or an abscess, suggests Crohn's disease.     

Portal vein thrombosis in Crohn's disease

Thromboembolic complications of inflammatory bowel disease are a well-recognized occurrence. Portal vein thrombosis has been reported in patients with ulcerative colitis but to date has not been reported in patients with Crohn's disease. We present the first case of portal vein thrombosis in a patient with Crohn's disease.     

Platelet factor 4 and beta-thromboglobulin in inflammatory bowel disease and giant cell arteritis

BACKGROUND: As platelet factors are important in the inflammatory response, we examined the course of platelet factor 4 and beta-thromboglobulin in relation to disease activity in inflammatory bowel disease and in giant cell arteritis. PATIENTS AND METHODS: In a prospective study, the platelet count, platelet factor 4 and beta-thromboglobulin were measured in 20 patients with Crohn's disease, 18 with ulcerative colitis and 19 with giant cell arteritis, during active and inactive disease, as well as in 51 controls without inflammation. RESULTS: Platelet counts were significantly higher in active vs. inactive Crohn's disease, ulcerative colitis and giant cell arteritis. Levels of platelet factor 4 and beta-thromboglobulin were significantly higher in active inflammatory bowel disease and giant cell arteritis, as well as in inactive inflammatory bowel disease and giant cell arteritis, than in the non-inflammatory controls. A positive correlation was found between the Crohn's disease activity index and the platelet count, platelet factor 4 and beta-thromboglobulin. Also, a positive correlation was found between the ulcerative colitis activity index and beta-thromboglobulin. However, even after 12 months of follow-up, in Crohn's disease and ulcerative colitis the mean levels of platelet factor 4 and beta-thromboglobulin were significantly higher than the levels of the controls. CONCLUSION: Platelet factors were correlated with inflammatory bowel disease activity. Levels of platelet factor 4 and beta-thromboglobulin, however, were markedly raised for a long time in clinically inactive inflammatory bowel disease, which might point to a pre-thrombotic state of disease.     

Small bowel and colonic permeability to 51Cr-EDTA in patients with active inflammatory bowel disease

51Cr-EDTA was administered both orally and per rectum via a catheter to controls and to patients with inflammatory bowel disease. The patients were divided into two groups, either with active inflammation of the small bowel or with active inflammation of the colon. Fifteen patients with Crohn's disease of the small bowel and 19 patients with either Crohn's disease of the colon or ulcerative colitis were investigated. After oral administration of the probe, controls showed a median excretion of 1.17%/24 h of the dose compared to 3.47%/24 h by patients with small bowel disease and 6.07%/24 h by patients with colonic disease. After rectal administration, controls showed a median excretion of 0.74%/24 h of the dose compared to 0.93%/24 h by patients with small bowel disease and 5.73%/24 h by patients with colonic disease. The rectal test differentiated small bowel disease from colonic disease with an accuracy of 85%. The results confirmed the inflamed colon as a site of increased intestinal permeation.     

Transrectal ultrasound in the diagnosis and management of inflammatory bowel disease

BACKGROUND AND STUDY AIMS: To aim of the present study was to determine the value of transrectal ultrasonography (TRUS) in the assessment of disease activity in ulcerative colitis patients, and in differentiating between mucosal inflammation and transmural inflammation. PATIENTS AND METHODS: TRUS examinations were used to study 30 control individuals and 76 patients with inflammatory bowel disease, including 50 cases of ulcerative colitis and 26 of Crohn's disease. A rigid linear endorectal probe was used to examine the rectal wall. RESULTS: In the 30 control individuals, the rectal wall showed five layers, with a mean total diameter of 2.6 mm. There were significant differences between patients with quiescent ulcerative colitis, active ulcerative colitis, and control individuals with regard to the total rectal wall thickness (P<0.001), submucosal thickness (P<0.001) and mucosal thickness (P<0.001). Using cut-off values, differentiation between active ulcerative colitis and remission ulcerative colitis was found to be 100% specific and 73 % sensitive for submucosal thicknesses. TRUS revealed a 100% specificity in differentiating between remission ulcerative colitis and control cases based on the total rectal wall thickness, submucosal, and mucosal thicknesses. In the differential diagnosis of active and remission ulcerative colitis, an increase in submucosal wall thickness and the existence of arterial and venous capillary flow in the submucosa were found to be specific and more sensitive than the other parameters. TRUS examination revealed transmural inflammation in 21 of the 26 Crohn's disease patients, and mucosal inflammation in all 50 of the ulcerative colitis patients. CONCLUSION: TRUS is a reliable and easy method of assessing ulcerative colitis activity and differentiating between rectal diseases.     

Chromium 51-ethylenediaminetetraacetate test: a useful test in the assessment of inflammatory bowel disease

We evaluated the usefulness of urinary excretion values in assessing mucosal damage in inflammatory bowel disease after administration of chromium 51-labeled EDTA either orally or rectally. In the oral study, 19 controls, 18 patients with Crohn's disease, and 13 patients with ulcerative colitis were given 100 microCi 51Cr-EDTA by mouth. The amount of 51Cr-EDTA in a 24-hour urine collection was expressed as a percentage of the ingested dose. The patients with Crohn's disease of the small bowel excreted 6.3% +/- 4.3%, which was significantly (P less than 0.001) higher than the percentage in patients with ulcerative colitis (1.7% +/- 1.1%) and controls (1.4% +/- 0.6%). In the enema study, 19 patients with ulcerative colitis, two with Crohn's disease, two with radiation colitis, and four controls (spastic colitis, lactose intolerance) were given 100 microCi 51Cr-EDTA by retention enema. The patients with active colonic inflammation excreted 8.4% +/- 3.9% of the dose given by enema, which was significantly (P less than 0.01) higher than in other controls (1.9% +/- 0.91%) or patients with inactive colitis (2.2% +/- 1.9%). The 51Cr-EDTA excretion test is a safe, inexpensive test useful in evaluating patients with inflammatory bowel disease. It can be given orally to screen patients with abdominal complaints who are suspected of having Crohn's disease involving the small intestine, and when given by enema it provides additional objective assessment of idiopathic ulcerative colitis or proctitis.     

Autoimmunity, Inflammatory Bowel Disease and Hyposplenism

The presence or absence of nine autoantibodies were assessedin 44 patients with ulcerative colitis (17 with hyposplenism)and 22 patients with Crohn's disease (eight with hyposplenism).The purpose of the study was to determine whether hyposplenismin inflammatory bowel disease is associated with an increasedtendency to autoimmunity, or whether autoimmunity is linkednot to hyposplenism itself but to the underlying bowel disease.The results strongly suggest that the latter hypothesis is correct.There was a much higher frequency of autoantibodies in patientswith ulcerative colitis than in those with Crohn's disease (P0.01),suggesting that autoimmune factors are more important in thepathogenesis of ulcerative colitis than in Crohn's disease.     

The humoral immune system in inflammatory bowel disease. II. Immunologlobulin levels

As there have been reports of differences in mean levels of serum immunoglobulins between patients with ulcerative colitis and Crohn's disease, serum IgG, IgA, and IgM were estimated in 158 patients with inflammatory bowel disease and the results correlated with the clinical features of the patients. Although a higher mean IgG level in ulcerative colitis compared to Crohn's disease was confirmed, no difference was found when the comparison was limited to patients with colonic Crohn's disease. Patients with either disease had higher mean IgM levels than controls, and the IgM levels were higher on treatment with corticosteroids and showed a tendency to rise in remission. IgG and IgM levels were also higher in both diseases if extraintestinal manifestations were present. It is concluded that if clinical features, particularly disease site, are taken into account, the overall immunoglobulin responses in these two diseases show no differences.     

In vitro cellular cytotoxicity in Crohn's disease and ulcerative colitis: relation with disease activity and treatment, and the effect of recombinant gamma-interferon

In a previous study using total mononuclear cells and lymphocytes, enriched by elutriation centrifugation, of patients with Crohn's disease and ulcerative colitis were found to have a decreased NK cell activity. In the present study the relation with disease activity and treatment, and the effect of recombinant gamma-interferon (gamma-IFN) on NK cell and monocyte cytotoxicity has been studied in 19 patients with Crohn's disease, 11 with ulcerative colitis, two with indeterminate colitis and 12 healthy controls. Patients with active Crohn's disease and active ulcerative colitis were shown to have an impaired NK cell activity compared to the control group. However, no difference was found in the percentage of CD16 (Leu 11+) cells, as determined by fluorocytometry, between patients with active or inactive disease. Moreover, the NK cell impairment was not related to corticosteroid treatment. Recombinant gamma-interferon (gamma-IFN) stimulated significantly the cytotoxic activity of the total mononuclear cells and the monocyte-enriched fraction against all target cell lines, both in patients and controls. No relation was found between the increase in cytotoxicity by gamma-IFN and disease activity in the patients. Stimulation with gamma-IFN demonstrated that the monocyte cytotoxic response of inflammatory bowel disease patients is normal. The present study reveals that the impairment in NK cell activity in patients with inflammatory bowel disease is related to disease activity and therefore suggests to be secondary to the inflammatory process.     

Low S-adenosylmethionine concentrations found in patients with severe inflammatory bowel disease.

BACKGROUND: S-adenosylmethionine is a methyl donor in many cellular reactions including detoxification of constantly produced hydrogen sulphide in the colon. A reduced capacity to detoxify hydrogen sulphide may be implicated in the pathogenesis of inflammatory bowel disease. S-adenosylmethionine could be low if this assumption is correct. We compared S-adenosylmethionine concentrations in whole blood in patients with severe and moderate inflammatory bowel disease with healthy reference persons. METHODS: S-adenosylmethionine concentrations in whole blood were measured using high-pressure liquid chromatography. Patients with Crohn's disease (n=21), ulcerative colitis (n=7) and healthy age-matched reference persons (or controls) (n=17) were studied. RESULTS: S-adenosylmethionine concentrations were significantly decreased in patients with severe inflammatory bowel disease (mean 1.10 mg/l) as compared to patients with moderate Crohn's disease and ulcerative colitis (mean 1.83 mg/l) and reference persons (mean 1.84 mg/l). Statistically significant inverse correlations were found between S-adenosylmethionine concentration and activity index (p<0.01 and R2=0.86) as well as Crohn's disease activity index (p<0.01 and R2=0.50) scores. CONCLUSIONS: Low concentrations of S-adenosylmethionine were found in patients with severe inflammatory bowel disease. Future studies will show whether S-adenosylmethionine is a marker for disease activity and a possible tool for investigation of sulphur toxicity as a causative mechanism in inflammatory bowel disease.     

C-reactive protein as an aid in the differentiation of functional and inflammatory bowel disorders

Eighty-two patients were investigated on their first visit to the outpatient department of St. Mark's Hospital, London, for the assessment of abdominal symptoms. In addition to the clinical examination, a rectal biopsy, routine tests and appropriate special investigations, blood was taken from each patient for the determination of erythrocyte sedimentation rate, C-reactive protein and alpha-1-acid glycoprotein. Nineteen patients were finally diagnosed as having Crohn's disease, twenty-two ulcerative colitis, and forty-one functional bowel disorders. All the patients with Crohn's disease had an elevated erythrocyte sedimentation rate and C-reactive protein level as had 11 (50%) of the patients with ulcerative colitis, but none with functional disorders. All cases of ulcerative colitis could be diagnosed by rectal biopsy. Measurement of alpha-1-acid glycoprotein provided no additional diagnostic information. A combination of rectal biopsy, and measurement of the erythrocyte sedimentation rate and C-reactive protein successfully distinguishes between inflammatory disease of the large and small bowel and functional bowel syndrome.     

Pericarditis associated with ulcerative colitis and Crohn's disease.

Extracolonic manifestations of inflammatory bowel disease are common and diverse. However, cardiac complications are unusual and we therefore wish to report two cases in which pericarditis occurred. The first was a patient with Crohn's disease of the colon, in whom the pericarditis developed postoperatively. In the second case an acute pericarditis came on simultaneously with the initial presentation of ulcerative colitis.     

Manipulation of cytokines in the management of patients with inflammatory bowel disease

In recent years, new concepts have been formulated for the therapeutic management of the intractable forms of Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease. These advances are based largely on new insights into the immune-inflammatory events occurring in the gut of these patients. Analysis of the types of immune response ongoing in the inflamed intestine has revealed that in Crohn's disease there is predominantly a T-helper cell type 1 response, with exaggerated production of interleukin (IL)-12 and interferon (IFN)-gamma, whereas in ulcerative colitis the lesion seems more of an antibody-mediated hypersensitivity reaction. Despite these differences, downstream inflammatory events are the same in both conditions. In both Crohn's disease and ulcerative colitis mucosa, IL-1gamma, IL-6, IL-8 and tumour necrosis factor (TNF)-alpha are produced in excess, and the production of free radicals accompanying the influx of nonspecific inflammatory cells into the mucosa is above the normal range. Strategies aimed at inhibiting T-cell responses are therefore more relevant in Crohn's disease, whereas, in theory at least, inhibition of downstream inflammatory processes should be therapeutic in both Crohn's disease and ulcerative colitis. This review seeks to summarize studies in which anticytokine antibodies, cytokines or cytokine-modifying agents have been used in the treatment of either Crohn's disease or ulcerative colitis.