Lack of association of the G22A polymorphism of the ADA gene in patients with ankylosing spondylitis.

Genes located outside the HLA region (6p21) have been considered as candidates for susceptibility to ankylosing spondylitis. We tested the hypothesis that the G22A polymorphism of the adenosine deaminase gene (ADA; 20q13.11) is associated with ankylosing spondylitis in 166 Brazilian subjects genotyped for the HLA*27 gene (47 patients and 119 controls matched for gender, age and geographic origin). The HLA-B*27 gene and the G22A ADA polymorphism were identified by PCR with sequence-specific oligonucleotide probes and PCR-RFLP, respectively. There were no significant differences in frequencies of ADA genotypes [odds ratio (OR) = 1.200, 95% confidence interval (CI) = 0.3102-4.643, P > 0.8] and ADA*01 and ADA*02 alleles (OR = 1.192, 95%CI = 0.3155-4.505, P > 0.8) in patients versus controls. We conclude that the G22A polymorphism is not associated with ankylosing spondylitis.

Pro-inflammatory cytokines up-regulate MUC1 gene expression in oral epithelial cells.

The membrane-bound mucin MUC1 is expressed ubiquitously on epithelial surfaces and is thought to provide protection from bacterial and chemical injury. The present study was undertaken to determine whether MUC1 was expressed in cultured oral epithelial cells and whether expression is modulated by pro-inflammatory mediators released as part of the host response to infection by oral pathogens. Northern and Western blotting experiments showed that KB cells express MUC1 mRNA and protein. When cells were treated with interleukins (IL-1beta, IL-6), tumor necrosis factor-alpha (TNF-alpha), or interferon-gamma (IFN-gamma), or combinations of these, real-time PCR demonstrated that MUC1 mRNA increased 1.4- to 3.2-fold. Interestingly, a significant increase in levels of MUC1 protein was also observed. While no effect was observed when KB cells were incubated with LPS from Porphyromonas gingivalis, infection of KB monolayers with this oral pathogen caused a 2.85-fold increase in MUC1 transcript levels. These results suggest that increased MUC1 synthesis may be a key element in the host response to infection with oral pathogens.

An assessment of digital image analysis to measure fibrosis in liver biopsy specimens of patients with chronic hepatitis C.

The aim was to assess the validity of a digitally computed fibrosis ratio as a measure of fibrosis stage in liver biopsy specimens. We scored 230 liver biopsy specimens from patients with chronic hepatitis C for fibrosis using modified Knodell criteria; fibrosis ratios were computed from digital images that encompassed the complete trichrome-stained section of each case. Although an overall correlation between fibrosis ratio and ordinal score was present, subset analysis showed that this correlation existed only among biopsy specimens with high scores (3-6, early bridging fibrosis to established cirrhosis). There was no correlation or difference between category means found among biopsy specimens with low scores (0-3, normal to early bridging fibrosis). Furthermore, concordance by both estimates in direction of fibrosis change among serial liver biopsy specimens was found in only 11 (30%) of 37 pairs compared. The findings suggest that a qualitative assessment of the computerized fibrosis pattern is necessary for the interpretation of computerized fibrosis ratio measurements, particularly in patients with early stage fibrosis.

No significant difference in antigenicity or tissue transglutaminase substrate specificity of Irish and US wheat gliadins.

The prevalence of clinical celiac disease has been shown to vary both across time and between genetically similar populations. Differences in wheat antigenicity and transglutaminase substrate properties are a possible explanation for these differences. This study assessed the antigenicity and transglutaminase substrate specificities of gliadins from regions of high and low celiac disease prevalence. Gliadin was extracted from three commercial US wheat sources and two Irish sources. SDS-PAGE and western blotting revealed minor, but significant variations in the gliadin extracts. However, ELISA showed no difference in the antigenicity of these gliadins. Transglutaminase pretreatment of gliadin resulted in no significant change in gliadin antigenicity and kinetic studies showed that the Kms of the various gliadins were very similar. Purified IgA and IgG had no effect on transglutaminase activity. In summary, minor variations in wheat gliadins are unlikely to explain the observed differences in disease expression across genetically similar populations.

A comparison of virtual and conventional colonoscopy for the detection of colorectal polyps.

BACKGROUND: Virtual colonoscopy is a new method of imaging the colon in which thin-section, helical computed tomography (CT) is used to generate high-resolution, two-dimensional axial images. Three-dimensional images of the colon simulating those obtained with conventional colonoscopy are then reconstructed off-line. We compared the performance of virtual and conventional colonoscopy for the detection of colorectal polyps. METHODS: We prospectively studied 100 patients at high risk for colorectal neoplasia (60 men and 40 women; mean age, 62 years). We performed virtual colonoscopy immediately before conventional colonoscopy. We inserted a rectal tube and insufflated the colon with air to the maximal level that the patient could tolerate. We administered 1 mg of glucagon intravenously immediately before CT scanning to minimize the degree of smooth-muscle spasm and peristalsis and to reduce the patient's discomfort. RESULTS: The entire colon was clearly seen by virtual colonoscopy in 87 patients and by conventional colonoscopy in 89. Fifty-one patients had normal findings on conventional colonoscopy. In the other 49, we identified a total of 115 polyps and 3 carcinomas. Virtual colonoscopy identified all 3 cancers, 20 of 22 polyps that were 10 mm or more in diameter (91 percent), 33 of 40 that were 6 to 9 mm (82 percent), and 29 of 53 that were 5 mm or smaller (55 percent). There were 19 false positive findings of polyps and no false positive findings of cancer. Of the 69 adenomatous polyps, 46 of the 51 that were 6 mm or more in diameter (90 percent) and 12 of the 18 that were 5 mm or smaller (67 percent) were correctly identified by virtual colonoscopy. Although discomfort was not specifically recorded, none of the patients requested that virtual colonoscopy be stopped because of discomfort or pain. CONCLUSIONS: In a group of patients at high risk for colorectal neoplasia, virtual and conventional colonoscopy had similar efficacy for the detection of polyps that were 6 mm or more in diameter.

Occlusive colon carcinoma: virtual colonoscopy in the preoperative evaluation of the proximal colon.

PURPOSE: To evaluate the use of preoperative virtual colonoscopy to examine the proximal colon in patients with distal occlusive carcinomas, defined as cancers that cannot be traversed endoscopically. MATERIALS AND METHODS: Twenty-nine patients with occlusive colorectal carcinomas underwent preoperative virtual colonoscopy with use of a standard protocol. Patients with acute bowel obstruction were excluded. Results of virtual colonoscopy were compared with the findings of preoperative colonoscopy, preoperative barium enema examination, intraoperative colon palpation, histopathologic outcome, and postoperative colonoscopy and barium enema examination, where possible. RESULTS: Virtual colonoscopy helped identify all 29 occlusive carcinomas and demonstrated two cancers and 24 polyps in the proximal colon. Both synchronous cancers were confirmed intraoperatively and resected. Postoperative conventional colonoscopy in 12 patients confirmed 16 polyps identified at virtual colonoscopy and demonstrated two subcentimeter polyps missed at virtual colonoscopy. Postoperative barium enema examination was performed in two patients and helped confirm two polyps identified at virtual colonoscopy. Virtual colonoscopy successfully demonstrated the proximal colon in 26 of 29 patients examined compared with preoperative barium enema examination, which failed to adequately demonstrate the proximal colon in any patient examined. CONCLUSION: Virtual colonoscopy is a feasible and useful method for evaluating the entire colon before surgery in patients with occlusive carcinomas.

A recombinant bovine gallbladder mucin polypeptide binds biliary lipids and accelerates cholesterol crystal appearance time.

BACKGROUND & AIMS: Mucin has a central role in the pathogenesis of cholesterol gallstones, in part because of its ability to bind biliary lipids and accelerate cholesterol crystal appearance time. Previous studies have localized these properties to nonglycosylated mucin domains, and we have recently shown that these domains contain a series of 127-amino acid, cysteine-rich repeats. The aim of this study was to express a recombinant mucin polypeptide containing these repeats and investigate its lipid-binding and pronucleating properties. METHODS: A recombinant mucin polypeptide was expressed as a glutathione S-transferase fusion protein in Escherichia coli, purified by affinity chromatography, and compared with native bovine gallbladder mucin in lipid-binding and cholesterol crystal appearance time assays. RESULTS: The recombinant mucin polypeptide bound a hydrophobic fluorescent probe and cholesterol in a concentration-dependent manner. It accelerated the appearance of cholesterol crystals from lithogenic model bile, an effect that was both time and concentration dependent. CONCLUSIONS: The cysteine-rich repeats in the recombinant mucin polypeptide correspond to the protease-sensitive hydrophobic domains identified in earlier biochemical studies. Further delineation of the lipid-binding site(s) in these repeats will provide new insights into the mechanism of cholesterol crystal nucleation and stone growth.

Colorectal neoplasm detection using virtual colonoscopy: a feasibility study.

BACKGROUND: Virtual colonoscopy is a potentially powerful tool for non-invasive colorectal evaluation. In vitro studies have established its accuracy in simulated polyp detection but little data exist regarding its use in clinical practice. AIMS: To evaluate the ability of virtual colonoscopy to detect colorectal cancers and polyps in patients with endoscopically proven colorectal neoplasms and to correlate the findings of virtual colonoscopy with those of conventional colonoscopy, surgery, and histopathology. PATIENTS: Thirty eight patients with endoscopic findings suggestive of colorectal carcinoma. METHODS: Virtual colonoscopy was performed using thin section helical computed tomography (CT) of the abdomen and pelvis after rectal insufflation of room air. Commercially available software was used to generate endoscopic "fly through" examinations of the colon from the CT data. Results were correlated with the findings of conventional colonoscopy and with the surgical and histopathological outcome in each case. RESULTS: Thirty eight pathologically proven colorectal cancers and 23 adenomatous polyps were present. On virtual colonoscopy, all cancers and all polyps measuring greater than 6 mm in size were identified; there were two false positive reports of polyps. On conventional colonoscopy, there was one false positive report of a malignant sigmoid stricture; four subcentimetre polyps were overlooked. Virtual colonoscopy enabled visualisation of the entire colon in 35 patients; conventional colonoscopy was incomplete in 14 patients. Virtual colonoscopy correctly localised all 38 cancers, compared with 32 using conventional colonoscopy. CONCLUSION: Virtual colonoscopy is a feasible method for evaluating the colon; it may have role in diagnosis of colorectal cancer and polyps.

The amino-terminal sequence of MUC5B contains conserved multifunctional D domains: implications for tissue-specific mucin functions.

The MUC5B mucin gene product is expressed in a wide variety of secretory epithelia including the gallbladder, salivary glands, trachea, and colon. Previous studies by us and others have described the C-terminal region as well as the central tandem repeating domain of this mucin. In an effort to understand the functional role of MUC5B in diverse human tissues, the sequence encoding the N-terminal region of this mucin was determined from the sequences of exons in three overlapping genomic clones. Primer extension mapped the site of transcription initiation 25 bp downstream from a putative TATA box element. The N-terminal region of MUC5B contained 1321 amino acids organized into a signal peptide, a short serine-threonine rich region, and three von Willebrand factor-like D domains. Comparison of this sequence with the N-terminal sequences of MUC2 and MUC5AC revealed a much higher degree of identity (46-59%) than that observed in the C-terminal regions of these mucins (33%). The N-terminal sequence of MUC5B also contains a number of sequence motifs common to several groups of extracellular ligand binding and adhesion proteins not previously recognized in mammalian gel-forming mucins. The N-terminal D domains in MUC5B are likely to have important roles in both mucin assembly and in the protective functions of the secreted mucin.

MUC4 is a major component of salivary mucin MG1 secreted by the human submandibular gland.

High molecular weight salivary mucin (MG1) is an important component of saliva, contributing to the lubricative and tissue-protective functions of this biological fluid. We have shown previously that the human mucin gene MUC5B is expressed at high levels in sublingual gland and is a significant constituent of MG1. Since many epithelia express multiple mucin genes, it seemed likely that MG1 in salivary secretions is also a heterogeneous mixture of mucin gene products. The aim of this study was to determine whether MUC4, a mucin shown in Northern blotting experiments to be expressed in salivary glands, was a significant protein component of MG1 in salivary secretions. Two cDNA clones containing MUC4 tandem repeats were isolated from a human submandibular gland cDNA library. In addition, recombinant MUC4 produced in a bacterial expression system cross-reacted with an antibody directed against deglycosylated MG1. This shows conclusively that human salivary mucin MG1 contains both MUC5B and MUC4 gene products suggesting that each mucin may perform distinct functions in the oral cavity.

Molecular characterization of a major high molecular weight mucin from human sublingual gland.

Human submandibular/sublingual gland secretions contain a multimeric high molecular weight mucin (MG1) and a monomeric low molecular weight mucin (MG2). MG2 is the product of the MUC7 gene, whereas the gene for MG1 has not been identified. Previously, we isolated a clone (pSM2-1) from a human sublingual gland cDNA expression library using an antibody against deglycosylated MG1 (Troxler et al., Biochem. Biophys. Res Commun., 217, 1112-1119, 1995). In order to identify the mucin gene from which pPM2-1 was derived, Northern blots of human submandibular and sublingual gland RNA were hybridized with a series of probes for tandem repeats found in the high molecular weight secreted mucins MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC6. The only known mucin expressed at high levels in sublingual gland was MUC5B, and no known mucin was expressed at high levels in submandibular gland. A series of overlapping clones was obtained by rescreening the sublingual gland cDNA library and by reverse transcriptase-polymerase chain reaction. The resulting clones connected pSM2-1 to a series of MUC5B tandem repeats at the 3' end of the repeat domain and provided the complete nucleotide and deduced amino sequence of the carboxyl terminal region of MG1. This region is enriched with respect to cysteine (approximately 10 mol %) and contained a D domain and a carboxyl terminal domain that could be aligned with the corresponding domains in human intestinal MUC2, human tracheobronchial MUC5AC, and human von Willebrand factor. The limited expression of known mucin genes, together with the considerable mucin synthesizing capacity of submandibular gland, suggests that a novel (previously not described) mucin gene is expressed in this gland and constitutes a portion of MG1 in salivary secretions.

CT colonoscopy of colorectal neoplasms: two-dimensional and three-dimensional virtual-reality techniques with colonoscopic correlation.

OBJECTIVE: The aim of this study was to compare the diagnostic accuracy of two-dimensional (2D) CT colonography and three-dimensional (3D) virtual colonoscopy with conventional colonoscopy in patients who have suspected colorectal neoplasms. SUBJECTS AND METHODS: Twenty patients were studied (eight women and 12 men; mean age, 53 years; range, 42-85 years). All patients had findings on conventional colonoscopy suggestive of colorectal carcinoma and underwent colonic CT within 3 hr of endoscopy. Two-dimensional CT colonography and 3D virtual colonoscopy images were generated from the same data set that was obtained from thin-section helical CT of the abdomen and pelvis after rectal insufflation of room air. Three-dimensional virtual colonoscopy images were obtained by downloading CT data to a workstation equipped with commercially available software. Volume- and perspective-rendering techniques were used to achieve interactive, 3D virtual "fly-through" examinations of the colonic mucosa. The results of 2D CT colonography and 3D virtual colonoscopy were compared with the findings of conventional colonoscopy and correlated with surgical and pathologic outcome where possible. RESULTS: Twenty masses (defined as intraluminal projections 2 cm or larger in diameter) and 15 polyps (defined as projections smaller than 2 cm in diameter) were identified in our study group. All masses and 14 of 15 polyps were successfully shown on 2D colonography. Three findings of polyps on 2D colonography were false-positive, and one was false-negative. Three-dimensional virtual colonoscopy revealed 19 of 20 masses and 13 of 15 polyps. On conventional colonoscopy, all 20 masses and 13 of 15 polyps were identified, with one false-positive finding of a malignant stricture in a normal colon. Complete examination of the colon was possible in 18 of 20 patients using the 2D technique and in 17 of 20 patients using 3D virtual colonoscopy, whereas conventional colonoscopy showed the entire colon in only 12 of 20 patients. CONCLUSION: Two-dimensional CT colonography and 3D virtual colonoscopy are complementary and effective techniques for examining the colon in patients with suspected colorectal carcinoma. CT techniques offer several advantages over conventional colonoscopy including the ability to detect abnormalities proximal to obstructing carcinomas, accurate localization of abnormalities within the colon, and good patient tolerance. These CT techniques may play an important role in future diagnosis of colorectal cancer and for screening patients at risk.

Molecular cloning of a major human gall bladder mucin: complete C-terminal sequence and genomic organization of MUC5B.

Gall bladder mucin has been shown to play a central role in the pathogenesis of cholesterol gallstone disease. While cloning and sequencing studies have provided a wealth of information on the structure of other gastrointestinal and respiratory mucins, nothing is known about the primary structure of human gall bladder mucin. In this study, we show that the tracheobronchial mucin MUC5B is a major mucin gene product expressed in the gall bladder. Antibodies directed against deglycosylated human gall bladder mucin were used to screen a gall bladder cDNA expression library, and most of the isolated clones contained repetitive sequences nearly identical with those in the tandem repeat region of MUC5B. An additional clone (hGBM2-3) contained an open reading frame coding for a 389 residue cysteine-rich sequence. The arrangement of cysteine residues in this sequence was very similar to that in the C-terminal regions of MUC2, MUC5AC and human von Willebrand factor. This cysteine-rich sequence was connected to a series of degenerate MUC5B tandem repeats in a 7.5 kb HincII genomic DNA fragment. This fragment, with ten exons and nine introns, contained MUC5B repeats in exon 1 and a 469 residue cysteine-rich sequence in exons 2-10 that provided a 152 nucleotide overlap with cDNA clone hGBM2-3. Interestingly, the exon-intron junctions in the MUC5B genomic fragment occurred at positions equivalent to those in the D4 domain of human von Willebrand factor, suggesting that these proteins evolved from a common evolutionary ancestor through addition or deletion of exons encoding functional domains.

Urinary assays for desmosine and hydroxylysylpyridinoline in the detection of cirrhosis.

BACKGROUND/AIMS: Non-invasive markers of liver fibrosis have great potential for both the diagnosis and therapy of liver disease and cirrhosis. The aim of this study was to evaluate the potential of urinary amino acids desmosine (DES) and isodesmosine (IDES) derived from the breakdown of elastin and hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) derived from fibrillar collagen in diagnosing chronic liver disease. METHODS: We studied 48 patients with chronic liver disease who had varying degrees of liver fibrosis, graded 0-6 using a modified Knodell score, and 20 control subjects without liver disease. Urinary DES (microg/g creatinine) and HP (nmol/mmol creatinine) were measured by an isotope dilution, high performance liquid chromatography method. For liver disease patients, aminoterminal propeptide of type III procollagen (PIIINP) and alanine aminotransferase were determined. The urine and serum markers were correlated to degree of fibrosis and inflammation on liver biopsies. Differences between groups were analyzed by ANOVA and multiple linear regression was applied to determine independence of variables. Sensitivity, specificity and receiver operating curves were derived for each marker. RESULTS: In the 17 patients with liver fibrosis score of 5-6, mean urinary DES, IDES, HP and LP were all significantly greater than in the control group (p<0.05). Urinary DES and IDES correlated best with fibrosis score, r=0.61 for both markers. The correlation coefficient between serum PIIINP and fibrosis score was 0.47. Urinary DES and HP each had an overall diagnostic accuracy of 77% for fibrosis. Combining markers improved accuracy to over 80%. No correlation was seen between the urinary markers and inflammation scores. CONCLUSIONS: Urinary DES and HP are potentially useful clinical markers for liver fibrosis, especially when used in combination or in association with PIIINP.

Interaction of bovine gallbladder mucin and calcium-binding protein: effects on calcium phosphate precipitation.

BACKGROUND & AIMS: Gallstones consist of calcium salts and cholesterol crystals, arrayed on a matrix of gallbladder mucin (GBM), and regulatory proteins like calcium-binding protein (CBP). To determine if interactions between CBP and GBM follow a biomineralization scheme, their mutual binding and effects on CaHPO4 precipitation were studied. METHODS: Binding of CBP to GBM was assessed by inhibition of the fluorescence of the complex of GBM with bis-1,8-anilinonaphthalene sulfonic acid (bis-ANS). The effects of the proteins on precipitation of CaHPO4 were assessed by nephelometry and gravimetry. Precipitates were analyzed for calcium, phosphate, and protein. RESULTS: CBP and bis-ANS competitively displaced each other from 30 binding sites on mucin, with a 1:1 stoichiometry and similar affinity. The rate of precipitation of CaHPO4 was retarded by mucin and CBP. Precipitate mass was unaffected by GBM alone but decreased with the addition of CBP. Complexing CBP with GBM abolished or moderated this latter effect, altered precipitate morphology, and changed the stoichiometric ratios of Ca to PO4 in the precipitates from 1:1 to 3:2. Mucin and CBP were incorporated into the precipitates. CONCLUSIONS: These studies suggest that the formation of calcium-containing gallstones is a biomineralization process regulated by both GBM and CBP.

Mucin-vesicle interactions in model bile: evidence for vesicle aggregation and fusion before cholesterol crystal formation.

Nucleation of cholesterol monohydrate crystals from bile is a critical step in the formation of cholesterol gallstones. Measurement of nucleation in model bile system and the characteristics of the initial nucleus have proven elusive. In this study we have used three separate physical chemical techniques to examine vesicle aggregation and fusion, including dynamic light scattering (DLS), transmission electron microscopy (TEM), and fluorescent biochemical assays. These assays enabled us to quantify the effect of biliary proteins, such as gallbladder mucin, on vesicle fusion and aggregation. In the absence of mucin, fusion is a relatively slow process occurring over 24 hours, whereas physiological concentrations of mucin are able to accelerate almost complete fusion of vesicles within 6 hours. Vesicle fusion and aggregation as characterized by TEM result in the formation of aggregates of multilamellar vesicles and giant fusion bodies associated with a background of mucin. These mucin-vesicle aggregate bodies may represent true nuclei and precede cholesterol monohydrate crystal nucleation. In future studies, these vesicle fusion assays can be used to quantitatively examine the effect of putative pro- and anti-nucleating proteins on the earliest steps of cholesterol crystal nucleation.

Bovine gall-bladder mucin contains two distinct tandem repeating sequences: evidence for scavenger receptor cysteine-rich repeats.

Gall-bladder mucin is a densely glycosylated macromolecule which is the primary secretory product of the gall-bladder epithelium. It has been shown to bind cholesterol and other biliary lipids and to promote cholesterol crystal nucleation in vitro. In order to understand the molecular basis for mucin-lipid interactions, bovine gall-bladder mucin cDNAs were identified by expression cloning and were isolated and sequenced. The nucleotide sequences of these cDNAs revealed two distinct tandem repeating domains. One of these domains contained a 20-amino acid tandem repeating sequence enriched in threonine, serine and proline. This sequence was similar to, but not identical with, the short tandem repeating sequences identified previously in other mammalian mucins. The other domain contained a 127-amino acid tandem repeating sequence enriched in cysteine and glycine. This repeat displayed considerable sequence similarity to a family of receptor- and ligand-binding proteins containing scavenger receptor cysteine-rich repeats. By analogy with other proteins containing these cysteine-rich repeats, it is possible that, in gall-bladder mucin, this domain serves as a binding site for hydrophobic ligands such as bilirubin, cholesterol and other biliary lipids.

Randomised comparison of olsalazine and mesalazine in prevention of relapses in ulcerative colitis.

Sulphasalazine extends remissions and lessens disease activity during relapses of ulcerative colitis, but it also causes many adverse side-effects. The adverse reactions are mostly attributable to the sulphapyridine carrier moiety rather than the active principle 5-aminosalicylic acid (5-ASA), so agents to deliver 5-ASA to the colon by other means have been designed. We have compared the efficacy and tolerability of two such agents, olsalazine and mesalazine, in maintenance therapy of ulcerative colitis. 100 patients with ulcerative colitis in remission were recruited at one centre and assigned randomly to treatment with olsalazine (Dipentum; 1.0 g daily) or mesalazine (Asacol, with Eudragit-S coating; 1.2 g daily). Compliance, biochemical and haematological variables, and clinical evidence of disease activity were assessed every 3 months for 12 months by observers unaware of treatment allocation. In intention-to-treat analysis, which included as treatment failures patients withdrawn for protocol violations, adverse reactions, intercurrent illness, or non-compliance as well as those with relapses of ulcerative colitis, the olsalazine group had a significantly lower rate of treatment failure than the mesalazine group (12/49 [24%] vs 23/50 [46%]; p = 0.025). Analysis restricted to 64 patients still in remission at 1 year and 18 with relapses also showed a significant difference in relapse rate (olsalazine 5/42 [12%] vs mesalazine 13/40 [33%]; p = 0.024). Both drugs were well tolerated; only 9 patients reported substantial side-effects. Olsalazine was clearly superior to mesalazine in prevention of relapses in ulcerative colitis, especially in patients with left-sided disease.