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.     

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.     

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.     

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.     

An investigation into the validity of the present classification of inflammatory bowel disease

To assess the validity of the present subdivision of patients with inflammatory bowel disease into those with Crohn's disease of the small bowel or of the colon and those with ulcerative colitis, 252 patients with inflammatory bowel disease have been studied by questionnaire and case note review. One hundred and seventy-two variables concerning the nature and frequency of symptoms in remission and relapse, the incidence of complications and results of investigation have been analysed by computer. As expected, there were many highly significant variables between patients with ulcerative colitis and those with Crohn's disease of the small bowel. The latter showed evidence of a more severe disease course with more complications. There were similar, although less marked, differences between patients with Crohn's disease of the colon and those with Crohn's disease of the small bowel. There were very few differences in disease course between patients with Crohn's disease of the colon and those with ulcerative colitis. The results suggest that while separate classification of patients with Crohn's disease of the small bowel is justified on clinical grounds, the present separation of patients with disease confined to the colon into groups labelled ulcerative colitis or Crohn's disease of the colon is not. Alternative methods of classification should therefore be investigated.     

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.     

Repeated measurement of intestinal permeability as an assessment of colitis severity in HLA-B27 transgenic rats.

We report on the development of a method for repeated monitoring of mucosal permeability that allows assessment of the severity of colitis and evaluation of treatment efficacy in HLA-B27 transgenic rats. We determined the extent to which intestinal permeability related to stool condition, colon weight, and histological pathology in precolitic and diseased rats up to 29 weeks old. Intestinal permeability was measured by the urinary excretion of iodixanol at 24 h after oral administration. Mean permeability values increased significantly with age in HLA-B27 rats but remained decreased in the background strain Fischer-344 (F-344) control animals. Macroscopic evaluation of HLA-B27 rat colons between 20 and 24 weeks old showed colonic thickening with colonic wet weights increased from 3.4+/-0.13 mg/kg b.wt. in F-344 rats to 6.79+/-0.73 mg/kg b.wt. (p<.05) in HLA-B27 rats. Histological examination of HLA-B27 rat colons confirmed the colonic inflammation as a chronic active mononuclear cell infiltrate. The increase in colon weight was associated with an increase in permeability: 1.16+/-0.17 mg iodixanol versus 5.37+/-1.3 mg of iodixanol in F-344 and HLA-B27 rats, respectively. Three weeks treatment of HLA-B27 rats with cyclosporin A, but not sulfasalazine, showed a dose-dependent decrease in mucosal permeability and colon weight. Neither treatment improved stool condition. We conclude that the measurement of intestinal permeability by iodixanol excretion is a useful biochemical marker that is associated with increases in colonic weight and histological evaluation of inflammation. These data indicate that this technique may be valuable for diagnostic and evaluation purposes in preclinical models of inflammatory bowel disease.     

Regional distribution and alterations of lectin binding to colorectal mucin in mucosal biopsies from controls and subjects with inflammatory bowel diseases.

Glycoconjugate composition of colorectal goblet cell mucin was characterized according to the anatomical distribution of lectin-binding sites in mucosal biopsies from 35 control subjects and 55 patients with inflammatory bowel disease. 24 of the controls had mucosal inflammation on biopsy, without clinical evidence of inflammatory bowel disease. These inflamed controls showed a similar rate of presence of lectin-binding sites as the normal noninflamed group. In the controls, the frequency of binding of Ricinus communis agglutinin I to galactosyl residues was consistently higher than that found with either Ulex europaeus agglutinin I to fucosyl or Dolichus biflorus agglutinin to N-acetyl galactosyl groups. A significant proximal to distal gradient for Ulex europaeus agglutinin I binding sites was identified in the controls group. These binding sites were present four times more often in the proximal colon than in the distal colon (P less than 0.025). In the ulcerative and Crohn's colitis groups, this gradient effect was lost, predominantly as a result of decreased availability of fucosyl residues in the proximal colon. In the descending colon of Crohn's colitis tissues, there was a complete absence of Dolichus biflorus agglutinin binding sites compared with the 62.5% incidence in the control group (P less than 0.05). These results demonstrate that the expression of lectin-binding sites in human large intestinal goblet mucin is specifically altered in inflammatory bowel disease, indicating that there are changes in glycosylation of colorectal mucin consistent with alterations in goblet cell differentiation.     

Detection of liver involvement in inflammatory bowel disease by abdominal ultrasound scan

Summary Fifty patients with ulcerative colitis, 24 with Crohn's disease, and 50 controls were studied by liver function tests and abdominal ultrasound scan. Twentytwo percent of ulcerative colitis patients, 29% of Crohn's disease patients, and none of the controls showed abnormal liver function tests. All subjects with abnormal liver function tests also had changes in ultrasound liver scan, consisting of hepatomegaly and/or a dysechoic liver echo pattern. Furthermore, the same ultrasound changes were observed, in the absence of any liver function test abnormalities, in 58% of ulcerative colitis patients, 50% of Crohn's disease patients and 6% of controls (P<0.0005, inflammatory bowel disease versus controls). Overall, some evidence of liver involvement, as judged by abnormal liver tests and/or abnormal ultrasound liver scan, was detected in about 80% of inflammatory bowel disease patients. Six patients with minor abnormalities of liver function tests underwent liver biopsy and 5 of them had pericholangitis. Ultrasound liver scan may provide a useful tool to evaluate the occurrence of liver involvement in inflammatory bowel disease patients.     

Detection of liver involvement in inflammatory bowel disease by abdominal ultrasound scan.

Fifty patients with ulcerative colitis, 24 with Crohn's disease, and 50 controls were studied by liver function tests and abdominal ultrasound scan. Twenty-two percent of ulcerative colitis patients, 29% of Crohn's disease patients, and none of the controls showed abnormal liver function tests. All subjects with abnormal liver function tests also had changes in ultrasound liver scan, consisting of hepatomegaly and/or a dysechoic liver echo pattern. Furthermore, the same ultrasound changes were observed, in the absence of any liver function test abnormalities, in 58% of ulcerative colitis patients, 50% of Crohn's disease patients and 6% of controls (P less than 0.0005, inflammatory bowel disease versus controls). Overall, some evidence of liver involvement, as judged by abnormal liver tests and/or abnormal ultrasound liver scan, was detected in about 80% of inflammatory bowel disease patients. Six patients with minor abnormalities of liver function tests underwent liver biopsy and 5 of them had pericholangitis. Ultrasound liver scan may provide a useful tool to evaluate the occurrence of liver involvement in inflammatory bowel disease patients.     

便秘主导型肠易激综合征患者结、直肠肛门动力学的临床研究--附50例检测分析

目的:研究便秘主导型肠易激综合征患者的结肠、直肠动力和直肠感觉功能.方法:用不透X线法的结肠传输试验检测50例便秘主导型肠易激综合征(constipation predominant irritable bowel syndrom,C-IBS)患者及42名正常受试者(对照组)的结肠传输时间(colonic transit time,CTT)和结肠传输指数(transit index,TI),并用结肠传输指数分型;同时用肛门直肠测压方法测定C-IBS患者和对照组的肛门直肠压力、直肠感觉阈值和直肠顺应性.结果:C-IBS患者的全结肠及各节段结肠传输时间均高于对照组,C-IBS患者的肛管静息压、直肠静息压与对照组比较差异均无统计学意义(P＞0.05),肛门括约肌最大收缩压低于对照组,最大耐受容量及直肠顺应性均明显高于对照组(P＜0.01),且发现不同传输类型的C-IBS患者的肛门直肠测压的结果不尽相同.结论:C-IBS患者存在结肠、肛门直肠动力及直肠感觉功能异常,结肠传输试验与肛门直肠测压相结合,更有助于明确便秘的类型.     

Effect of the leukotriene B4 receptor antagonist SC-41930 on colonic inflammation in rat, guinea pig and rabbit

Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract that includes ulcerative colitis and Crohn's disease. Leukotriene B4 is thought to be a prominent proinflammatory mediator in these diseases, in that leukotriene B4 levels are increased in the colonic mucosa of inflammatory bowel disease patients and there is increased polymorphonuclear leukocyte infiltration of these tissues. We evaluated the efficacy of 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-3,4-dihydro-8-propyl -2H-1-benzopyran-2-carboxylic acid (SC-41930), a potent, orally active leukotriene B4 receptor antagonist, in a model of inflammatory bowel disease. Colonic mucosal inflammation was induced in rats, guinea pig and rabbits by rectal instillation of a dilute solution of acetic acid. Twenty-four hours later, mucosal levels of myeloperoxidase (a marker enzyme for neutrophil infiltration) and extravasation of i.v. administered Evans blue dye (a marker of vascular disruption and increased permeability) were measured. Tissues were also evaluated histologically. The animals received either SC-41930 or vehicle, intrarectally, 30 min after or 1 hr before and 1 hr after the acetic acid. When given 30 min after acetic acid instillation SC-41930 prevented the rise in myeloperoxidase and dye extravasation observed in the acetic acid inflammed tissue. The SC-41930-treated tissues were less edematous and had fewer neutrophils within the subepithelial space. Median effective dose (ED50) values for vascular protection were approximately 20 mg/kg for both rat and guinea pig. ED50 values for inhibition of granulocyte accumulation were 20 mg/kg for rat, 24 mg/kg for guinea pig and 30 mg/kg for rabbit. These data indicate that SC-41930 is effective locally to prevent acute colonic inflammation.     

Differences in brain responses to visceral pain between patients with irritable bowel syndrome and ulcerative colitis

Patients with mild chronic inflammation of the rectum or ileum have reduced perceptual responses to rectosigmoid distension compared to patients with irritable bowel syndrome (IBS). The current study sought to identify differences in regional cerebral blood flow (rCBF) during rectal distension, which might correspond to these perceptual differences. In 8 male ulcerative colitis (UC) patients with quiescent disease, 7 male IBS patients and 7 healthy male controls, rCBF was assessed using 15O-water positron emission tomography at baseline and during actual and anticipated but undelivered rectal distensions. No group differences were seen in anterior insula and dorsal anterior cingulate cortex (dACC), two regions consistently activated by painful intestinal stimuli. However, IBS patients showed greater activation of the amygdala, rostroventral ACC, and dorsomedial frontal cortical regions. In contrast, no significant differences were observed between UC and controls. When these two non-IBS groups were combined, functional connectivity analyses showed that right lateral frontal cortex (RLFC) activation positively correlated with activation of the dorsal pons/periaqueductal gray, a key region involved in endogenous pain inhibition. According to the connectivity analysis, this effect was mediated by inhibition of medial frontal cortex by the RLFC. Chronic colonic inflammation is not necessarily associated with increased visceral afferent input to the brain during rectal distension. In the sample studied, the primary difference between functional and quiescent inflammatory disease of the colon was in terms of greater activation of limbic/paralimbic circuits in IBS, and inhibition of these circuits in UC and controls by the RLFC.     

Sulphation of colonic and rectal mucin in inflammatory bowel disease: reduced sulphation of rectal mucus in ulcerative colitis.

1. Normal colonic mucin is heavily sulphated and this increases its resistance to degradation by bacterial enzymes. Any defect in mucus sulphation could therefore be important in the pathogenesis of ulcerative colitis. 2. Rectal biopsies taken at colonoscopy from patients with ulcerative colitis (n = 9), patients with Crohn's disease (n = 6) and control subjects (n = 16) were cultured for 24 h in the presence of N-[3H]acetylglucosamine and [35S]sulphate. Mucin was then extracted and purified, and the ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into pure mucin was assessed. 3. The ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into mucin was significantly reduced in rectal biopsies taken from patients with ulcerative colitis (0.463, 0.305-0.703, geometric mean and 95% confidence intervals) compared with control subjects (0.857, 0.959-1.111, P < 0.01). In patients with Crohn's disease the reduction in this ratio (0.559, 0.378-0.829) did not quite reach statistical significance (P = 0.06). There was no difference between the ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into mucin in Crohn's disease and that in ulcerative colitis (P = 0.26). 4. In control subjects the ratio of [35S]sulphate to N-[3H]acetylglucosamine incorporated into mucin was higher in the rectal biopsies (0.882, 0.618-1.022) than in their paired proximal colonic biopsies (0.602, 0.421-0.861; P < 0.01), but this regional variation was not observed in either ulcerative colitis (rectum: 0.450, 0.262-0.773; right colon: 0.470, 0.321-0.690, P = 0.3) or Crohn's disease (rectum: 0.459, 0.260-0.815; right colon: 0.492, 0.260-0.929, P = 0.8).(ABSTRACT TRUNCATED AT 250 WORDS)     

Neutrophil apoptosis is delayed in patients with inflammatory bowel disease

Delayed neutrophil apoptosis is a feature of persistent acute inflammation. Neutrophil-mediated damage has been shown to be associated with the development of inflammatory bowel disease (IBD). Persistence of these cells both at the colonic site and circulation may further contribute to IBD. The aims of this study were to determine whether neutrophils isolated from IBD patients delay apoptosis and to investigate possible mechanisms involved in this delay. We studied 20 patients with IBD, 13 with Crohn's disease, and 7 with ulcerative colitis, all of whom were undergoing intestinal resection for symptomatic disease. Seventeen patients undergoing elective resection of colon cancer acted as operative controls. Systemic, mesenteric arterial, and mesenteric venous blood was harvested. Neutrophils isolated from patients with IBD showed decreased spontaneous apoptosis compared to cancer patients. Mesenteric venous serum of IBD patients contributed to this delay, which contained higher concentrations of interleukin-8 (IL-8). Pro-caspase 3 expression was also reduced in IBD neutrophils, which may contribute to decreased spontaneous and Fas antibody-induced apoptosis. Neutrophil apoptosis may be altered in Crohn's disease and ulcerative colitis through release of anti-apoptotic cytokines and altered caspase expression. The alterations in cell death mechanisms may lead to persistence of the inflammatory response associated with IBD.     

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.     

Increased arachidonic acid levels in phospholipids of human colonic mucosa in inflammatory bowel disease

1. Colonic mucosa from 19 patients with ulcerative colitis, eight with Crohn's disease and 14 controls were analysed for arachidonic acid (C20:4), linoleic acid (C18:2), oleic acid (C18:1), stearic acid (C18:0) and palmitic acid (C16:0). 2. Gas-liquid chromatography of lipid extracts showed that arachidonic acid was significantly higher in ulcerative colitis (19 +/- 4) and Crohn's disease (20 +/- 3) than in controls (13 +/- 5 micrograms/mg of protein) (means +/- SD). Neither the degree of inflammation nor treatment with sulphasalazine or prednisolone appeared to influence the fatty acid concentrations. 3. Seventy-five to ninety-five per cent of the arachidonic acid was found in the phospholipid fraction after separation by thin-layer chromatography. There were no significant changes in the concentrations of the other fatty acids measured, although oleic acid was lower in inflammatory bowel disease. The ratios of oleic acid to stearic acid and to palmitic acid were lower in inflammatory bowel disease. 4. The alteration in the fatty acid profile may partly explain the increased synthesis of eicosanoids in colonic mucosa in inflammatory bowel disease.     

Clinical relevance of measuring colonic permeability

Background  Gastroduodenal and small intestinal permeability are increased in patients with Crohn's disease (CD) and intensive care patients. The relevance of colonic permeability has not yet been adequately investigated. The aim of this study was to investigate the clinical value of sucralose excretion as indicator for colonic permeability in these patient groups.
Design  After oral administration of four sugars and subsequent analysis of urinary excretion, gastroduodenal and intestinal permeability were calculated from saccharose excretion and lactulose/mannitol (L/M) ratio over 5 h, and sucralose excretion from 5 to 26 h in 100 healthy controls, 29 CD and 35 patients after coronary surgery (CABG).
Results  In controls, sucralose excretion was highly variable (0·67 ± 0·92%) and not related to small intestinal permeability. In CD and CABG, L/M ratio was increased (0·054 ± 0·060; 0·323 ± 0·253 vs. 0·018 ± 0·001 in controls). Sucralose excretion was increased in 77% of CABG but only in 7% of CD. There was an association between gastroduodenal and intestinal permeability in CD and CABG ( r  = 0·72, and r  = 0·51), but sucralose excretion was not related to either one of these two parameters. Other than a weak association between sucralose and length of stay in intensive care in CABG patients ( P  = 0·099), sucralose excretion was not related to clinical outcome.
Conclusions  The proposed cut-off for normal sucralose excretion is 2·11%, but its high variability and lack of association to gastrointestinal permeability or clinical outcome leave it open, if it can provide information beyond established permeability tests.     

Cyclic adenosine 3', 5' monophosphate: a possible indicator of premalignant changes in the large bowel.

Cyclic adenosine 3', 5' monophosphate (cyclic-AMP) has been estimated in mucosal biopsy samples removed from the descending colon and rectum at endoscopy to investigate the possibility of using this substance for monitoring pre-malignant changes in the large bowel. Four groups of patients have been studied: those with normal large bowel and rectal mucosa; those with non-malignant inflammatory bowel disease; those with an adenomatous polyp in the descending colon or sigmoid colon; and those with a rectal adenocarcinoma. No difference was found in the cyclic-AMP content of 'normal' rectal mucosa, 'normal' colonic mucosa, 'diseased' colonic mucosa, carcinomas, and uninvolved mucosa adjacent to the polyps. Less cyclic-AMP was found in the polyps than in adjacent uninvolved mucosa. Conversely, more cyclic-AMP was found in the carcinomas than in adjacent uninvolved mucosa. It is concluded that although cyclic-AMP may be a very useful parameter for delineating the extent of the disease in individual patients, it is not a suitable biochemical marker for the screening of neoplastic changes in the large bowel in the population as a whole.     

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.