Poor diagnostic value of colonic CD44v6 expression and serum concentrations of its soluble form in the differentiation of ulcerative colitis from Crohn's disease

Background—Increased expression ofCD44v6 on colonic crypt epithelial cells in ulcerative colitis has beensuggested as a diagnostic tool to distinguish ulcerative colitis fromcolonic Crohn's disease.
Aims—To investigate colonicCD44v6 expression and serum concentrations of soluble CD44v6 (sCD44v6)in patients with ulcerative colitis and Crohn's disease.
Methods—Colonic biopsy samples wereobtained from 16 patients with ulcerative colitis, 13 with ileocolonicCrohn's disease, and 10 undergoing polypectomy. Serum samples wereobtained from 15 patients with active ulcerative colitis, 20 withactive Crohn's disease, and 20 healthy donors. Colonic CD44v6expression was evaluated immunohistochemically by monoclonal antibody2F10 and the higher affinity monoclonal antibody VFF18. Serum sCD44v6concentrations were measured by ELISA.
Results—2F10 stained colonicepithelium of inflamed ulcerative colitis and Crohn's disease samplesin 80% and 40% of cases, respectively, and VFF18 in 95% and 87%,respectively. Both monoclonal antibodies displayed a sensitivity andspecificity of 60% and 87% to differentiate ulcerative colitis fromcolonic Crohn's disease. Serum concentrations of sCD44v6 were lower inpatients with ulcerative colitis (median 153 ng/ml; interquartile range(IQR) 122-211) compared with Crohn's disease (219; IQR 180-243) andhealthy donors (221; IQR 197-241 (p=0.002)). Its sensitivity andspecificity to discriminate ulcerative colitis from Crohn's diseasewas 75% and 71%, respectively.
Conclusion—Colonic CD44v6 and serumsCD44v6 concentrations do not facilitate reliable differentialdiagnosis between ulcerative colitis and Crohn's disease.

Keywords:CD44 variant 6; differential diagnosis; immunohistochemistry; soluble CD44v6

     

Visualising E-selectin in the detection and evaluation of inflammatory bowel disease

Background—Vascular endothelial E-selectin expression is induced by proinflammatory cytokines andcontributes to accumulation of leucocytes in tissues.
Aims—To investigate the role ofE-selectin in inflammatory bowel disease (IBD).
Methods—E-selectin expression wasassessed in patients with ulcerative colitis and Crohn's disease bymeasuring the concentration of circulating soluble E-selectin(sE-selectin) using ELISA, by immunohistochemistry of colonic biopsyspecimens, and by abdominal immunoscintigraphy after injectingradiolabelled F(ab')₂ fragment of a monoclonalanti-E-selectin antibody. The value of scintigraphy usinganti-E-selectin was judged by a prospective comparative study ofautologous leucocyte scanning and E-selectin antibody scanning in 17 patients with IBD.
Results—Circulating sE-selectin waselevated in patients with clinically active disease. Tissue expressionof E-selectin was enhanced in patients with active inflammation, withweak or absent expression in inactive disease and healthy controls.In-111 labelled anti-E-selectin scintiscans were compared with Tc-99mlabelled leucocyte scans performed 24 hours earlier. Twelve patientshad areas of active inflammation on leucocyte scan while 11 patients had positive E-selectin scans. The results of the two scans were concordant in 14 patients, with those positive for both (10/17) showingsimilar disease localisation and extent.
Conclusions—Tissue E-selectinand circulating sE-selectin are increased during active inflammatorybowel disease. Anti-E-selectin imaging with radiolabelled monoclonalantibody identified areas of inflammation in Crohn's disease andulcerative colitis. The technique should prove useful clinically foridentifying the site and extent of disease.

Keywords:E-selectin; inflammatory bowel disease; Crohn'sdisease; ulcerative colitis

     

Crohn's-like reaction in diverticular disease

Background—Diverticulitis and Crohn's diseaseaffecting the colon occur at similar sites in older individuals, and incombination are said to carry a worse prognosis than either disease inisolation. It is possible that diverticulitis may initiate inflammatorychanges which resemble Crohn's disease histologically, but do notcarry the clinical implications of chronic inflammatory bowel disease.
Aims—To evaluate histological features andclinical outcome in individuals initially diagnosed histologically ashaving both Crohn's colitis and diverticulitis.
Patients—Eleven consecutive individuals having acolonic resection showing histological features of both Crohn'sdisease and diverticulitis.
Methods—Retrospective review of histologicalspecimens, case notes, and discharge letters.
Results—In nine patients, the Crohn's-likereaction was confined to the segment bearing diverticula. They had noclinical evidence of Crohn's disease.
Conclusion—A Crohn's-like inflammatory responsecan be a localised reaction to diverticulitis and does not necessarilyindicate chronic inflammatory bowel disease.

Keywords:Crohn's disease; diverticulitis; colitis; histology

     

Monozygotic twins with Crohn's disease and ulcerative colitis: a unique case report

Background—A large number of monozygotic anddizygotic twin pairs with inflammatory bowel disease have beenreported. To date no twin pair has developed phenotypically discordantinflammatory bowel disease. This case report is the first documentedoccurrence of discordant inflammatory bowel disease occurring inmonozygotic twins.
Case report—Twenty two year old identical maletwins presented within three months of each other with inflammatorybowel disease that proved to be discordant in overall disease type,disease distribution, clinical course, and histopathological findings. Twin 1 developed a severe pancolitis necessitating total colectomy while twin 2 developed a predominantly distal patchy colitis with frequent granulomas, controlled by aminosalicylates. Twin 1 was antineutrophil cytoplasmic antibody (ANCA) negative at the time oftesting while twin 2 (Crohn's disease) was ANCA positive.Significantly, the twins possessed the HLA type DR3-DR52-DQ2 previouslyassociated with extensive colitis.
Conclusion—This case report confirms the importantrole played by genetic factors in the development of inflammatory bowel disease. It also highlights the crucial role of undeterminedenvironmental agents in dictating disease expression and phenotype.

Keywords:monozygotic twins; ulcerative colitis; Crohn'sdisease; inflammatory bowel disease

     

Appendicectomy, childhood hygiene, Helicobacter pylori status, and risk of inflammatory bowel disease: a case control study

Aims—To examine the relation between inflammatorybowel disease and appendicectomy, childhood domestic hygiene, andHelicobacter pylori infection.
Methods—Case control study involving 213 patientswith ulcerative colitis, 110 with Crohn's disease, and 337 controlshaving elective surgery.
Results—Nine patients with ulcerative colitis(4.5%) reported a previous appendicectomy compared with 57 controls(19%) (odds ratio (OR) 0.20, 95% confidence interval (CI) 0.1-0.4,p<0.0001). The inverse association was unaffected by excludingoperations performed after the age of onset of ulcerative colitis andwas stronger for appendicectomy performed before age 20 (OR 0.14). Noassociation with appendicectomy was found for Crohn's disease and noassociations with tonsillectomy for either disease. The availability ofa fixed hot water supply in early childhood (before age 11) wasassociated with Crohn's disease (OR for hot water not always versusalways available 0.56, 95% CI 0.3-0.9, p=0.02) but not withulcerative colitis. No other aspect of domestic hygiene before or afterage 11 was associated with either Crohn's disease or ulcerativecolitis. Although H pylori seroprevalence was positively associated with overcrowding (p<0.001) and the absence of running hotwater in childhood it was not associated with the presence of eitherCrohn's disease or ulcerative colitis. H pyloriseroprevalence was no lower in patients who had been exposed tosulphasalazine than in controls or those not exposed.
Conclusions—Our findings confirm the stronginverse association between previous appendicectomy and the developmentof ulcerative colitis and suggest that the protective effect is greaterfor appendicectomy performed in childhood.

Keywords:inflammatory bowel disease; appendicectomy; tonsillectomy; childhood hygiene; Helicobacter pylori; sulphasalazine

     

Expression of cell membrane complement regulatory glycoproteins along the normal and diseased human gastrointestinal tract

Background/Aims—Uncontrolled complementactivation may be of immunopathological importance in inflammatorydiseases of the gastrointestinal tract. Expression of membrane boundfactors that regulate complement activation was therefore studied in situ.
Methods—Frozen tissue specimens were obtained frompatients with Helicobacter pylori gastritis, coeliacdisease, Crohn's disease, or ulcerative colitis, and fromhistologically normal controls. Sections were examined byimmunofluorescence with monoclonal antibodies to protectin (CD59),decay accelerating factor (DAF), and membrane cofactor protein (MCP).
Results—Protectin and MCP were widely expressed innormal and diseased mucosae. MCP was generally observed basolaterallyon all epithelial cells, whereas apical protectin expression was moreintense on the epithelium of normal colonic mucosa than in the normalduodenum (p = 0.001). Epithelial DAF and to some extent protectin wereupregulated in gastritis, coeliac disease, and inflammatory boweldisease. Areas of the stomach with intestinal metaplasia expressed DAF,unlike the adjacent gastric epithelium. Parietal cells of the gastricbody expressed neither protectin nor DAF.
Conclusion—Epithelial complement inhibitorymolecules were expressed differently at various normal gastrointestinalsites and also in association with mucosal disease, suggesting variable protective potential. Such molecules could play a role in the development of gastric atrophy by protecting areas of intestinal metaplasia. Conversely, parietal cells appeared to be potentially vulnerable targets for complement attack.

Keywords:Helicobacter pylori; coeliac disease; Crohn's disease; ulcerative colitis; immunofluorescence; complementregulatory proteins

     

Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease

Background—Reactive oxygen species contribute totissue injury in inflammatory bowel disease (IBD). The tripeptideglutathione (GSH) is the most important intracellular antioxidant.
Aims—To investigate constituent amino acid plasmalevels and the GSH redox status in different compartments in IBD withemphasis on intestinal GSH synthesis in Crohn's disease.
Methods—Precursor amino acid levels were analysedin plasma and intestinal mucosa. Reduced (rGSH) and oxidisedglutathione (GSSG) were determined enzymatically in peripheral bloodmononuclear cells (PBMC), red blood cells (RBC), muscle, and innon-inflamed and inflamed ileum mucosa. Mucosal enzyme activity ofγ-glutamylcysteine synthetase (γGCS) and γ-glutamyl transferase(γGT) was analysed. Blood of healthy subjects and normal mucosa froma bowel segment resected for tumour growth were used as controls.
Results—Abnormally low plasma cysteine and cystinelevels were associated with inflammation in IBD (p<10^-4).Decreased rGSH levels were demonstrated in non-inflamed mucosa (p<0.01) and inflamed mucosa (p=10^-6) in patients withIBD, while GSSG increased with inflammation (p=0.007) compared withcontrols. Enzyme activity of γGCS was reduced in non-inflamed mucosa(p<0.01) and, along with γGT, in inflamed mucosa(p<10^-4). The GSH content was unchanged in PBMC, RBC, and muscle.
Conclusions—Decreased activity of key enzymesinvolved in GSH synthesis accompanied by a decreased availability ofcyst(e)ine for GSH synthesis contribute to mucosal GSH deficiency inIBD. As the impaired mucosal antioxidative capacity may further promote oxidative damage, GSH deficiency might be a target for therapeutic intervention in IBD.

Keywords:Crohn's disease; ulcerative colitis; glutathione; amino acids; γ-glutamylcysteine synthetase; mucosa

     

Low dose oral pH modified release budesonide for maintenance of steroid induced remission in Crohn's disease

Background—The relapse rate after steroid inducedremission in Crohn's disease is high.
Aims—To test whether oral pH modified releasebudesonide (3 × 1 mg/day) reduces the relapse rate and to identifypatient subgroups with an increased risk of relapse.
Methods—In a multicentre, randomised, doubleblind study, 179 patients with steroid induced remission of Crohn'sdisease received either 3 × 1 mg budesonide (n=84) or placebo (n=95)for one year. The primary study aim was the maintenance of remission ofCrohn's disease for one year.
Results—Patient characteristics at study entrywere similar for both groups. The relapse rate was 67% (56/84) in thebudesonide group and 65% (62/95) in the placebo group. The relapsecurves in both groups were similar. The mean time to relapse was 93.5days in the budesonide group and 67.0 days in the placebo group. Noprognostic factors allowing prediction of an increased risk for relapseor definition of patient subgroups who derived benefit from low dosebudesonide were found. Drug related side effects were mild and nodifferent between the budesonide and the placebo group.
Conclusion—Oral pH modified release budesonide ata dose of 3 × 1 mg/day is not effective for maintaining steroidinduced remission in Crohn's disease.

Keywords:budesonide; Crohn's disease; maintenance ofremission

     

Different microcirculatory and interstitial matrix patterns in idiopathic dilated cardiomyopathy and Chagas' disease: a three dimensional confocal microscopy study

OBJECTIVE—To analyse the morphological aspects of the extracellular matrix and microcirculation to clarify whether chronic Chagas' cardiopathy (CCC) is an accurate model to study the pathogenesis of idiopathic dilated cardiomyopathy (IDCM).
DESIGN—Thick histological myocardial sections were prepared to analyse collagen, and microcirculation was examined during confocal laser and light microscopy.
SETTING—The specimens were prepared at the pathology service of the Heart Institute of São Paulo, Brazil.
PATIENTS—Nine control hearts, eight IDCM hearts, and 10 CCC hearts were studied after necropsy.
MAIN OUTCOME MEASURES—The number of collagen struts per 100× field, the area of fibrosis (%), and the diameters of arterioles and capillaries were measured in each heart to establish outcome.
RESULTS—A smaller number (mean (SD)) of collagen struts was seen in the hearts in the IDCM group (9.1 (4.1)) than in the control (22.4 (3.2)) (p < 0.05) or CCC (15.7 (7.4)) (p > 0.05) groups. Fibrosis was greater in the CCC hearts (13.8 (10.5)%) than in the IDCM hearts (5.9 (6.6)%) (p > 0.05). Major increases in arteriole (65.4 (9.9) µm) and capillary (9.9 (1.7) µm) diameters were seen in the CCC hearts but not in the IDCM hearts (arteriole diameter 40.3 (7.9) µm; capillary diameter 7.9 (1.3) µm).
CONCLUSIONS—Hearts demonstrating CCC and IDCM present different extracellular and microvessel alterations. This suggests that distinct pathogenic mechanisms are responsible for each condition and that CCC is not an effective model to study IDCM.


Keywords: microcirculation; Chagas' disease; dilated cardiomyopathy; extracellular matrix     

A simple clinical colitis activity index

Background—The appropriate medicaltreatment of patients with ulcerative colitis is determined largely bythe severity of symptoms. Hospital assessment of the severity ofdisease activity includes investigation of laboratory indices andsigmoidoscopic assessment of mucosal inflammation.
Aims—To develop a simplifiedclinical colitis activity index to aid in the initial evaluation ofexacerbations of colitis.
Methods—The information fordevelopment of the simple index was initially evaluated in 63 assessments of disease activity in patients with ulcerative colitiswhere disease activity was evaluated using the Powell-Tuck Index (whichincludes symptoms, physical signs, and sigmoidoscopic appearance). Thenew index was then further evaluated in 113 assessments in a differentgroup of patients, by comparison with a complex index utilisingclinical and laboratory data, as well as five haematological andbiochemical markers of disease severity.
Results—The newly devised SimpleClinical Colitis Activity Index, consisting of scores for five clinicalcriteria, showed a highly significant correlation with the Powell-TuckIndex (r=0.959, p<0.0001) as well as thecomplex index (r=0.924, p<0.0001) and alllaboratory markers (p=0.0003 to p<0.0001).
Conclusions—This new Simple ColitisActivity Index shows good correlation with existing more complexscoring systems and therefore could be useful in the initial assessmentof patients with ulcerative colitis.

Keywords:ulcerative colitis; disease activity