bluuebunny/crossref_metadata_2025 huggingface dataset:
CLINICAL COURSE IN KOREAN PATIENTS WITH ULCERATIVE COLITIS
Authors: Kim WH , Choi CH , Lee CR , Ahn SH , Kim TI , Park IS
Published: January 2004

During recent several years, the incidence of ulcerative colitis is rapidly increasing in Korea. Both patients and physicians await good predictors of individual clinical course in terms of morbidity. We wanted to analyse not only clinical features in ulcerative colitis at the time of diagnosis, but also clinical courses during 5 years after diagnosis. Factors affecting clinical courses were also investigated.

Methods  One hundred and seventy‐four patients with ulcerative colitis regularly followed at least 1 year, spanning from January 1988 to October 2000, were included. Morbidity was evaluated using annual disease burden index, defined as summation of monthly clinical severity (0 for remission, 1 for mild, 2 for moderate, and 3 for severe). Multiple variables such as, demographic parameters, social history, symptoms, duration before diagnosis, extent of disease, endoscopic as well as clinical severity, laboratory data including ANCA and treatment, were used to identify factors affecting clinical course.

Results  Mean annual disease burden index at first, third and fifth year after diagnosis was 5.8 ± 4.4, 4.9 ± 5.3, and 3.8 ± 4.1, respectively. Mean annual symptomatic period also decreased from 4.0 ± 3.1 months at first year to 3.0 ± 3.4 months in fifth year. Presence of fever at the time of diagnosis was the only factor affecting annual disease burden index and symptomatic period at first year after diagnosis. Cumulative relapse free at 1, 2, and 5 years after diagnosis were 58.2, 68.2 and 86.8%, respectively. Young age at onset (< 30), short extent of disease (proctitis and left‐sided colitis vs. extensive colitis), and history of transfusion were factors significantly related with higher relapse rate (P < 0.05, log–rank test).

Conclusion  Disease burden index and symptomatic period in each year tend to decrease with time during 5 years after diagnosis. Cumulative relapse rate in Korean patients with ulcerative colitis was comparable to that in Western countries and was affected by age at onset, extent of disease, and history of transfusion.
CLINICAL PRESENTATION OF CROHN'S DISEASE IN PAKISTAN
Authors: Khan Rustam , Abbas Zaigham , Memon Sadik , Hamid Saeed , Shah Hasnain , Jafri Wasim
Published: January 2004

Introduction  Crohn's disease is uncommon in Pakistan and local demographic data is not available. Due to high prevalence of intestinal tuberculosis, it is often misdiagnosed and mismanaged. Aim of this study is to review the clinical presentation of Crohn's disease in our region.

Methods  Medical records of 475 adult patients admitted during the last 13 years with label of Crohn's disease were reviewed for the presence of Crohn's disease. Symptoms and signs, activity of the disease, site of involvement and the management offered was recorded.

Results  Diagnosis of Crohn's disease was made in 52 patients (29 females, 23 males). Mean age was 40.1 + 14.1 years. Disease was classified as inflammatory in 71%, obstructive in 15% and fistulizing in 14% cases. Disease activity was mild in 62%, moderate in 34% and severe in 4% cases. Pancolitis with skip lesions was the most common presentation present in 24 (46%) patients. Out of these 11 (21%) patients also had terminal ileum involvement. Ileocaecel disease was seen in only nine (17%) and isolated ileal disease in three (6%) patients. Another 11 (21%) patients showed one‐sided colitis. Predominant symptoms were diarrhea (88%), abdominal pain 83%, bleeding per‐rectum (52%), weight loss (48%), fever (37%), loss of appetite (27%), anal pain (10%) and jaundice (6%). Abdominal tenderness was present in 60%, pallor in 52% and abdominal mass in 15%. Anal signs were present in 25% of patients and included tags, fissures and abscesses. Extra intestinal manifestations were arthritis in seven (13%), sclerosing cholangitis in four (7.6%) and ankylosing spondylitis in two (3.8%). The patients were treated with steroids, 5‐aminosalisylic acid, azathiprine, metronidazole and antibiotics. Decision‐making was difficult in five patients who were initially treated with antituberculous drugs.

Conclusion  Crohn's disease exists in Pakistan and should be considered in the differential diagnosis of inflammatory diseases of colon and intestine. It is important to rule out tuberculosis in these cases. The disease activity in our region is usually mild to moderate with predominant inflammatory pattern. Colon is most common site of involvement.
COBALAMIN DEFICIENCY and SMALL BOWEL BACTERIAL OVERGROWTH: A COMMON ASSOCIATION
Authors: Chitti L , Cummins AG
Published: January 2004

Background  Bacterial overgrowth may cause cobalamin deficiency through competition for dietary cobalamin in the small intestine. The objective of this study was to prospectively determine the prevalence of small bowel bacterial overgrowth in patients with documented cobalamin deficiency in a tertiary referral centre.

Methods  Patients identified with cobalamin deficiency underwent diagnostic investigations including: Endoscopy (with gastric antrum, gastric body and duodenal biopsies and duodenal aspirate), 14C‐D‐Xylose breath test, intrinsic factor antibody, anti‐endomysial antibody and red cell folate level. ‘Definite’ small bowel bacterial overgrowth was defined as either a positive 14C‐D‐Xylose breath test or > 100 000 CFU/mL of culture of duodenal aspirate. ‘Suspected’ small bowel bacterial overgrowth was defined as an elevated red cell folate in the absence of supplemental folate therapy.

Results  Over a 2‐year period, 62 patients with cobalamin deficiency were identified, of whom, 26 (42%) had ‘definite’ small bowel bacterial overgrowth, whilst a further nine (15%) had ‘suspected’ small bowel bacterial overgrowth. Nineteen (31%) had pernicious anaemia, and no cause for cobalamin deficiency could be found in eight (13%) patients. The diagnosis found in the remaining patients included coeliac disease (4), Crohn's Disease (1), gastric resection (2), vegan (2), homozygotes of the MTHFR gene (C677T) mutation (2), and one had enteropathy associated with common variable immunodeficiency (CVID). ‘Definite’ small bowel bacterial overgrowth was found to coexist with nine of the 19 cases of pernicious anaemia, two coeliac subjects, one CVID enteropathy and one patient with the MTHFR gene mutation.

Conclusion  Small bowel bacterial overgrowth is commonly associated with cobalamin deficiency.
COLONIC DYSPLASIAS IN IBD PATIENTS ARE LESS FREQUENT THAN EXPECTED
Authors: Ochsenkühn Thomas , Tillack Cornelia , Stepp Herbert , Ott Stephan J , Baumgartner Reinhold , Göke Burkhard , Sackmann Michael
Published: January 2004

Objectives  Patients with long‐standing IBD have an increased risk to develop colonic dysplasias, however, by conventional colonoscopy dysplasias are likely to be missed. Endoscopic fluorescence imaging is a promising new technique to differentiate between normal colonic mucosa and dysplasia. We, therefore, used this technique to prospectivly evaluate the occurence of dysplasias in patients with longstanding IBD‐colitis.

Methods  Twenty‐five consecutive patients with longstanding IBD‐colitis were screened for colonic dysplasias. To induce tumor‐selective intracellular synthesis of red‐fluorescent protoporphyrin IX, its precursor, 5‐aminolevulinic acid, was given orally at a dose of 1 g. Patients were examined by both conventional white light colonoscopy and by fluorescence imaging using a blue light source (400–410 nm) and a sensitive camera to detect fluorescence (D‐Light/Tricam SL, Storz, Germany). Biopsies were taken every 10 cm from normal appearing mucosa, from macroscopically suspicious areas, and from fluorescence‐positive areas.

Results  The median duration of the IBD was 14 years. Fluorescence was negative in all but one patient. However, in this one patient, histology revealed no dysplastic tissue, thus the rate of false‐positive results was only 4%. In none of the biopsies dysplasias were detected histopathologically.

Conclusions  Thorough endoscopic examination with a dense net of biopsies, in addition to fluorescence analysis, revealed no dysplasias in the colon of 25 patients with longstanding IBD‐colitis. These data show that the rate of colonic dysplasias in patients with long‐standing IBD‐colitis may be lower than previously reported.
COLONOSCOPIC SCREENING FOR FAMILY HISTORY OF COLORECTAL CANCER: ARE NHMRC GUIDELINES BEING FOLLOWED?
Authors: Yusoff Ian , Hoffman Neville , Ormonde Donald , Aitken James , Ee Hooi
Published: January 2004

Aims  The NHMRC has published recommendations for screening of patients with a family history of colorectal cancer (CRC). We aimed to assess if referrals and follow‐up recommendations in an open access colonoscopy service concur with these guidelines.

Methods  We prospectively interrogated patients referred for colonoscopy with a family history of CRC concerning the number, relationship and age of such relatives, to assess whether they satisfied NHMRC criteria for screening. Follow‐up recommendations were also assessed retrospectively.

Results  From January 2000 to April 2001 2579 colonoscopies were performed. There were 340 cases with a family history of CRC and 202 of these were asymptomatic. Of these screening cases, mean age was 50 years (range 16–80 years). Referrals were from general practitioners in 92%, gastroenterologists in 5% and other specialists in 2% of cases.

NHMRC category
Number of patients in category
Satisfied all NHMRC criteria for  colonoscopic screening at referral

Unable to classify
3
0

1
84
0

2
107
87

3
8
8

Total
202
95

There were 87 patients who did not satisfy the criteria for colonoscopic screening (Unable to classify or Category 1). Of these, 25 (29%) were below the recommended age to commence any screening. There were 115 patients (57%) who satisfied the family history criteria for colonoscopic screening (NHMRC Category 2 or 3). Of these, 20 (17%) were below the recommended age to commence screening. Follow‐up recommendations were made in 108 patients (53%) and these concurred with NHMRC guidelines in 88 cases (81%). In 16 of the 20 cases where follow‐up recommendations did not occur with NHMRC guidelines, the interval to repeat colonoscopy was too short or colonoscopy was recommended rather than annual faecal occult blood testing.

Conclusions  Less than half the patients being referred for screening colonoscopy for family history of CRC satisfy NHMRC criteria. In the majority of cases this is due to referral of Category 1 patients for screening. Follow‐up recommendations, when made, are usually in keeping with NHMRC guidelines.
COMBINATION ANTI‐PARATUBERCULOSIS THERAPY WITH CLARITHROMYCIN, RIFABUTIN and CLOFAZIMINE IN THE TREATMENT OF CROHN'S DISEASE. A PRELIMINARY REPORT ON THE AUSTRALIAN MULTICENTRE TRIAL
Authors: Selby W , Crotty B , Florin T , Pavli P , Morrow AW
Published: January 2004

Mycobacterium paratuberculosis has been proposed as the cause of Crohn's disease, although this remains controversial. Observational studies of antibiotics with activity against this organism have led to the establishment of an Australian multicentre placebo‐controlled trial of clarithromycin, rifabutin and clofazimine in patients with active Crohn's disease. All subjects receive treatment with a tapering regimen of prednisolone for the initial 16 weeks, combined with either antibiotics or matching placebos. If remission is achieved at the end of this period and prednisolone has been ceased they continue the trial medications for 2 years. The primary outcomes – remission rates at 1, 2 and 3 years – aim to determine whether these antibiotics are of long‐term benefit in Crohn's disease. Secondary outcomes include rate of remission at 4 months, safety and quality of life.

As of May 2001, 171 of the required 212 subjects have been enrolled. Eighty‐seven of 146 potential subjects have reached 16 weeks in remission (60%). Eighty of these are ongoing (92%). Only five withdrawals from the trial have occurred for adverse events thought probably related to trial medications – four subjects with raised LFTs and one who developed a rash. Other withdrawals have been mainly due to lack of response or worsening of Crohn's disease (37), hypomania from steroids (one patient) and pregnancy (one patient on placebo). There have been 11 withdrawals for protocol violations. An Independent Data Monitoring Committee has analysed progress of the trial and unanimously recommended that it continue.

This study is the largest and longest suitably powered randomised controlled trial of antibiotics undertaken in Crohn's disease. It will determine whether this antibiotic combination alters the natural history of this disorder.

This study is being supported by Pharmacia Australia Pty Limited.
COMBINING WHEAT BRAN WITH RESISTANT STARCH RAISED FAECAL BUTYRATE and LOWERED FAECAL PHENOLS IN HUMAN VOLUNTEERS CONSUMING A DIET HIGH IN RED MEAT
Authors: Muir JG , Yeow EGW , Keogh J , Bird T , Pizzey CJ , Macrae FA
Published: January 2004

Fermentation of undigested carbohydrates [non‐starch polysaccharides (NSP) and resistant starch (RS)] and protein in the colon may contribute to the aetiology of colorectal cancer (CRC). Byproducts of carbohydrate fermentation include the short chain fatty acids (SCFA) acetate (Ace), propionate (Prop) and butyrate (Buty). Butyrate inhibits proliferation of CRC cells in vitro and may induce differentiation and apoptosis. Products of protein fermentation include tumorigenic ammonia and phenols (p‐cresol and phenol). The aim of this study was to investigate the effect of combining unprocessed wheat bran (WB) with RS on fermentation‐dependent events in the distal colon of on a diet high in lean red meat. The study was a randomised crossover block design of a total of 11 weeks (including 3 × 3 weeks of dietary study and 2 × 1 week breaks between dietary periods). Twenty volunteers (10 female) with a family history of CRC were randomized to either Diet 1 (control diet = 250 g red meat/day + low RS + low WB); Diet 2 [WB diet = 250 g red meat/day + low RS + unprocessed WB (10 g dietary fibre/day)] or Diet 3 [WB/RS diet = 250 g red meat/day + RS (25 gRS/day) + WB (10 g dietary fibre/day)]. Lean red meat, RS (coarsely ground Himaize™) and WB were supplied. All food and drink consumed during the study was recorded. During the final week of each 3 week dietary period subjects collected total faecal output for 5 days (days 15–19) for analysis of faecal variables (see Table). Rectal biopsies were taken on the morning of day 20 (analysis in progress).

Diet
Faecal output  (g/day)
Faecal SCFA(mmol/L)
Faecal SCFA (mmol/day)
Phenols (μg/g faeces)

Ace
Prop
Buty
Ace
Prop
Buty
Phenol
p‐cresol

1
131 ± 14
59 ± 4
16 ± 1
15 ± 1
8 ± 1
2 ± 0.3
2 ± 0.3
3.1 ± 5
102 ± 71

2
161 ± 15
59 ± 4
14 ± 1
16 ± 1
10 ± 1
2.5 ± 0.3
3 ± 0.4
3.4 ± 5
81 ± 46

3
204 ± 19
68 ± 5
14 ± 1
26 ± 3
14.6 ± 2
2.8 ± 0.3
6 ± 1
1.8 ± 4
61 ± 42

Mean ± SD; Faecal variables in italics are significantly different (P < 0.05) in test diet vs. Control diets.

The combination of unprocessed wheat bran and RS had a greater impact on fermentation‐dependent events (i.e. increased faecal output, increased butyrate concentration and lowered faecal phenols) than WB alone (Table). The combination of WB and RS may have important implications for the dietary modulation of CRC risk especially in the distal colon. The results also highlight the benefits of increasing dietary intake of indigestible carbohydrate relative to protein sources such as meat.
COMPARATIVE ANALYSIS OF THE MUCOSAL ASSOCIATED MICROBIOTA (MMB) IN CROHN'S DISEASE (CD) and NON‐IBD CONTROL SUBJECTS
Authors: Wang Xin , Heazlewood Sharise , Florin Timothy
Published: January 2004

The cause(s) of CD are not known, but its pathogenesis depends on the interaction of enteric bacteria and food antigen products with the mucosal immune system. Accumulated evidence clearly demonstrates that enteric microbiota influence the ontogeny and behavour of the innate and acquired mucosal immune system. Although there are significant enteric bacteria resident in the lumen of the human colon (up to 1013/g wet faeces), it is microbiota that associate with mucosa of intestinal epithelium (MMB) that are more likely to influence the mucosal immune system, to effect inflammation or tolerance.

Aims  To analyse the MMB communities in CD vs. ulcerative colitis (UC) and non‐IBD subjects using molecular ecological approach.

Methods  Total DNA are extracted from washed colonoscopic biopsy samples from macroscopically non‐involved CD (to date, n = 6 ileum and n = 1 colon), ulcerative colitis (n = 1 colon) and non‐IBD (n = 2 terminal ileum, n = 1 colon). Bacterial 16s‐rDNA are amplified by PCR with universal bacterial primers. After cloning, the diversity of bacterial communities are characterized by RFLP pattern analysis (ribotyping). Bacteria are then identified by phylogenetic analysis of DNA sequences of individual RFLP patterns.

Results  There was significantly more bacterial DNA in CD than non‐IBD with mean total DNA (ng) in amplicons in ileal samples from CD subjects, 39.2, compared with non‐IBD, 4.25 and in CD colon, 24.6, compared with non‐IBD colon, 13.4 ng (Mann–Whitney, P = 0.014). Bacteroides sp. were numerically predominant both in four of seven CD and three of three non‐IBD biopsy samples. five of seven CD biopsies had a striking number of bacterial clones phylogenetically identified to belong to Clostridium cluster XIVa (13–36%) vs. 0–9% in non‐IBD controls and 11% in UC colon. The three CD with low bacteroides and lower Clostridium cluster XIVa (4–11%), had a high frequency of Pseudomonas spp. (19–40%), together with high occurrence of Klebsiella spp., as did one of three non‐IBD controls (36%) and the UC biopsy (11%).

Conclusions  CD ileum may harbour an abnormal and more abundant resident MMB. Further study is required to describe the heterogeneous MMB in both normal and IBD ileum and colon. One of the XIVa species is extremely mucolytic. A Pseudomonas has recently been implicated in CD. The full 16s‐rDNA sequences of two XIVa species and the Pseudomonas spp. are being obtained, as well as specific PCR primers to screen a larger number of biopsies for the presence of these bacteria.
CORTICOTROPIN‐RELEASING HORMONE (CRH) MRNA EXPRESSION IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS (PVN) DURING EXPERIMENTAL COLITIS IN THE RAT
Authors: Kojima Kensaku , Wakabayashi Naoki , Mitsufuji Shoji , Ibata Yasuhiko , Tanaka Masaki
Published: January 2004

Background  Neuroendocrine–immune interactions can influence processes arising from the brain, and there is evidence that the central nervous system may amplify or modulate aspects of intestinal inflammation through alterations of the autonomic nervous system activity and/or stimulation of the hypothalamic–pituitary–adrenal (HPA) axis (American Journal of Physiology 276: G1027, 1999). But the effect of the colitis itself on the HPA axis remains unclear.

Aim  To investigate the effect of experimental colitis on the HPA‐axis, especially on CRH mRNA expression in the PVN, plasma adenocorticotropin (ACTH) and corticosterone (CORT) level.

Methods  Under isoflurane anesthesia, male SD rats (250–300 g) were induced to colitis by intracolonic administration of 0.2 mL of 50% ethanol (v/v) containing 20 mg of 2,4,6‐trinitrobenzenesulfonic acid (TNBS). In the first experiment, rats were sacrificed before and on days 1, 3, 7 and 14 after induction of colitis, and CRH mRNA levels in the PVN were quantified by in situ hybridization, plasma ACTH and CORT levels were measured by radioimmunoassay, and the colonic damage was assessed by measurement of colonic myeloperoxidase (MPO) activity. In the second experiment, rats were adrenalectomized bilaterally and corticosterone pellet was implanted subcutaneously (ADX + CORT). On day 3 after ADX + CORT, rats were infused TNBS (TNBS group) or saline (saline group) rectally and CRH mRNA level, plasma ACTH and CORT levels were measured on day 7 after administration of TNBS or saline. In the third experiment, pair‐fed rats whose daily food intake was matched to that of their pair in the colitic group were used, and on day 7 after treatment, CRH mRNA level, plasma ACTH and CORT levels were measured.

Results  In the first experiment, CRH mRNA levels in the PVN on days 3 and 7 after induction of colitis were significantly lower than those before induction of colitis (P < 0.05, P < 0.01, respectively). Plasma CORT levels during colitis were increased significantly (P < 0.001) from days 1 to 14, and plasma ACTH levels showed no significant change after day 3. In the second experiment, CRH mRNA level in the PVN in the TNBS group was significantly higher than those in the saline group (P < 0.01). In the third experiment, pair feeding resulted in no significant change in CRH mRNA, plasma ACTH and CORT levels.

Conclusions  These findings indicated that CRH mRNA expression in the PVN was inhibited by glucocorticoid feedback during this experimental colitis, and the decrease in food intake during colitis was not simply responsible for the expression of CRH mRNA.
CpG ISLAND METHYLATION and CHROMOSOME 1P LOSS IN ABERRANT CRYPT FOCI
Authors: Chan Annie On On , Broaddus Russell R , Issa Jean‐Pierre J , Hamilton Stanley R , Rashid Asif
Published: January 2004

Aberrant crypt foci (ACF) are postulated to be the earliest precursor in colorectal carcinogenesis. CpG island methylator phenotype has been described as another pathway for colorectal cancer. We studied CpG island methylation (CIM) at p16, MINT1, MINT2, MINT31, MGMT, and hMLH1, loss of heterozygosity at chromosome 1p, K‐ras mutation, and microsatellite instability in 27 ACF from patients with familial adenomatous polyposis (FAP) and 34 ACF from patients with sporadic colorectal cancer (CRC). CIM was present in 33% (21 of 61) of ACF: 2% at three loci, 13% at two loci and 20% at one locus. K‐ras mutation and chromosome 1p loss were present in 25% (15 of 61) and 10% (3 of 31) of ACF, respectively. K‐ras mutations (P = 0.007) and chromosome 1p loss (P = 0.01) were more common in ACF with CIM. CIM (P = 0.03) and K‐ras mutation (P = 0.01) were more common in ACF from sporadic patients. Methylation and chromosome 1p loss are early event in the pathogenesis of colorectal carcinomas, and ACF from FAP patients and patients with sporadic CRC have distinct phentoypic, genetic and epigenetic changes.
ACCEPTABILITY OF VIRTUAL COLONOSCOPY AS A COMMUNITY BASED CRC SCREENING TEST IN ASYMPTOMATIC AVERAGE RISK SUBJECTS
Authors: Edwards JT , Foster NM , Wood CJ , Mendelson RM , Forbes GM
Published: January 2004

Objectives  The acceptability of virtual colonoscopy (VC) in an average risk colorectal cancer (CRC) screening population is unknown. Our aims were to (1) assess acceptability of VC and (2) compare this with colonoscopy (CY), in a community based screening programme.

Methods  Randomly selected asymptomatic average risk subjects aged 50–54 or 65–69 years were invited to participate in a VC based CRC screening programme. Virtual colonoscopy involved a sodium picosulfate (picolax) based bowel preparation, hyoscine butylbromide (buscopan) injection, rectal insertion of Foley's catheter, inflation of the bowel by CO2 and supine and prone CT scans. Of 174 (M:F 91:83) subjects who have completed screening by VC, 43 had a positive VC and underwent CY on the same day. CY subjects received a mean sedation of midazolam 3.4 mg, pethidine 59 mg. All participants completed questionnaires following their procedure (s).

Results Visual analogue scale questionnaire results (median scores). (0 = most favourable, 100 = least favourable)

Pain
Tolerated
General satisfaction
Level of embarrassment
How likely to do again

All VC n = 174
16
11
6
7
5

VC and CY n = 43

 VC
17
17
7.5
5
4

 CY
4
5
2.5
2
2

Was procedure better, worse or similar to expected?

Better (%)
Similar (%)
Worse (%)

All VC n = 174
50
43
7

CY n = 43
88
9
3

VC
CY
No preference

Preferred procedure (n = 43)
7
14
22

Conclusion  VC is a highly acceptable screening test. The vast majority of subjects would readily have either VC or CY again.
DIFFERENTIAL DIAGNOSIS OF INTESTINAL BEHCET'S DISEASE and CROHN'S DISEASE BY COLONOSCOPIC FINDINGS
Authors: Kim TI , Kim WH , Lee J‐H , Lee CR , Kang JK , Lim JK
Published: January 2004

Both Crohn's disease and intestinal Behçet's disease can cause nonspecific ulcerative lesion in any part of the intestine. The differential diagnosis between these two diseases is often difficult due to lack of pathognomic findings. The aims of this study were to investigate the colonoscopic findings and to find valuable parameters in differentiation between Crohn's disease and Behçet's disease.

Methods  From August 1989 to June 2000, 183 patients were diagnosed as Crohn's disease (82) or intestinal Behçet's disease (101). We evaluated endoscopic features of 170 patients (100 patients with Intestinal Behçet's disease and 70 patients with Crohn's disease) who had ulcerative lesions on colonoscopy. Classification and regression tree method was used for the differentiation of two diseases by colonoscopic findings.

Results  The distribution of lesions was divided into 3 types; focal (single or multiple), segmental, and diffuse. Most (93%) of the lesions in intestinal Behçet's disease distributed focally, in contrast many (70%) of the lesions in Crohn's disease showed segmental or diffuse distribution. The shape of ulcer was commonly round/oval (68%) or irregular (24%) in intestinal Behçet's disease while longitudinal (49%) or irregular (30%) in Crohn's disease. The ulcer in intestinal Behçet's disease tended to deeper, and more discrete than that in Crohn's disease. Stricture, inflammatory polyp, and perianal lesion were more common in Crohn's disease. Statistically these characteristics could make a tree structured classification rule as follows (Hit ratio: 91.9%).

Round/oval  Intestinal Behçet's disease

Ulcer Irregular Focal distribution Intestinal Behçet's disease

Segmental or diffuse distribution Crohn's disease

Longitudinal  Crohn's disease

Conclusion  The shape of ulcer and distribution of lesions were the two most distinguishable endoscopic features. Round/oval ulcer was the characteristics in intestinal Behçet's disease, and longitudinal ulcer was that in Crohn's disease. When the ulcer was irregular, focal distribution suggested intestinal Behçet's disease, while segmental or diffuse distribution suggested Crohn's disease.
DIFFERENTIAL EXPRESSION ANALYSIS OF MICROSATELLITE UNSTABLE COLORECTAL CANCERS IDENTIFIES NOVEL GENE TARGETS
Authors: Whitehall Vicki L J , Jass Jeremy R , Young Joanne , Leggett Barbara A
Published: January 2004

Molecular profiling of sporadic colorectal cancers has led to the demarcation of three distinct groups: those with a high level of microsatellite instability (MSI‐H), low level of instability (MSI‐L) and microsatellite stable tumours (MSS) (no instability). Each subclass can be characterised by a number of distinguishing genetic features which effect the phenotype and drug responsiveness of the tumour and may indicate patient prognosis. Tumours arise as a result of altered protein function and this is associated with concomitant alteration in gene expression levels. Based on this premise, suppressive subtractive hybridisation (SSH) was utilised to identify genes down‐regulated in MSH‐H tumour cells when compared with the corresponding normal mucosa. In addition to amplifying differentially expressed genes, this technique suppresses the amplification of high copy number genes and therefore selects for expression differences in rare transcripts. Two subtraction experiments were performed in parallel with varying starting material. SSH1 utilised paired normal and tumour tissue from an MSI‐H cancer. SSH2 used pure MSI‐H tumour cells after passage in a nude mouse paired with colonic crypts isolated from the corresponding normal mucosa. The subtracted libraries were cloned and 400 randomly picked colonies from each SSH were subjected to a secondary screen to confirm differential expression. All remaining clones were sequenced and compared with known genes through the ANGIS nonredundant nucleic acid databases to identify clones which had been isolated in duplicate or from different regions of the same gene. Contiguous sequences were constructed using the Sequencher assembly program. This resulted in a total of 146 unique clones of which 31 matched known sequences. Four clones were isolated from both SSH experiments. The differentially expressed genes included those associated with transcription, checkpoint control, DNA mismatch repair, ion transport, mucin synthesis, metabolism, apoptosis and cell adhesion. Novel cDNA clones were further characterised bioinformatically to identify putative open reading frames, functional domains and chromosomal location. SAGE and virtual northern analysis confirmed many clones to be of colonic origin, often isolated from normal mucosa and down‐regulated in tumours. Clones were prioritised for further study based on known functional relevance, presence of coding region repeat tract or 5′ CpG island which may allow epigenetic gene silencing by methylation. Detailed functional significance of known genes and confirmatory expression analysis of selected candidates will be discussed. This technique has been proven sensitive for the detection of functionally relevant and novel genes in the progression of MSI‐H tumours, which may provide novel points of therapeutic intervention.
DIFFERENTIAL EXPRESSION OF ZONA OCCLUDEN‐1 PROTEIN and ITS ALPHA SPLICE ISOFORMS IN CROHN'S DISEASE and ULCERATIVE COLITIS
Authors: Ooi Choon Jin , Ng Han Seong , Podolsky Daniel K
Published: January 2004

Introduction and aims  Tight junctions (TJ) are critical in sustaining the epithelial barrier. We investigated the regulation of major TJ proteins in IBD, the MAGUK (membrane associated guanylate kinase) cytoplasmic proteins, Zona occluden (ZO)‐1 and ZO‐2. Two isoforms of TJ protein ZO‐1 exist as a result from alternative RNA splicing and they differ by an internal 80‐amino acid domain termed motif‐α. ZO‐1 a– is expressed in structurally dynamic junctions whereas ZO‐1 α+ is expressed in less dynamic cells; perhaps this differentiation may correlate with the differences in junction plasticity, but the role of these different isoforms have never been studied in IBD.

Methods  Mucosal biopsies were obtained from patients with Crohn's disease (CD), and ulcerative colitis (UC) undergoing colonoscopies. Colonoscopic biopsies were taken from macroscopically ‘involved’ (I) and ‘not involved’ (NI) areas avoiding ulcerated areas. Control specimens were obtained from patients undergoing colonoscopies with no history or endoscopic evidence of inflammatory or infective processes. TJ proteins were evaluated by immunoblotting, and mRNAs encoding these TJ proteins were assessed by RT–PCR and Northern blotting. Cellular localization of TJ proteins was defined by immunofluorescence (IF). β‐Actin proteins were used as internal controls. A total of 40 patients were studied; 10 normal, 16 UC and 14 CD patients.

Results  Immunoblotting revealed down‐regulation of ZO‐1, and ZO‐2 in IBD tissues. In addition, RT–PCR showed that ZO‐1α+ isoform predominated in the normal tissue while the ZO‐1α– isoform was increased in disease. Our results show that both isoforms exists in normal intestinal tissue, with the ZO‐1α– consisting 14% (SD 0.05) of total ZO‐1. However, the proportion of ZO‐1α–/total ZO‐1 increased to 29% (P < 0.05) in uninvolved CD tissues, 40% (P < 0.01) in inflamed CD tissues and 46% (P < 0.001) in inflamed UC tissues. Northern blots employing DNA probes encoding both splice variants of ZO‐1 documented a decrease in steady state RNA in diseased tissues. IF showed ZO‐1 localized to dense granules on apical surfaces in normals, but was more cytoplasmic in distribution in IBD tissues.

Conclusion  Alteration in ZO‐1 expression may be specific changes to CD and UC. This is the first study to show up‐regulation of the ZO‐1α– in inflamed tissues in CD and UC. It is however, unclear if these changes are the primary event to leading to breakdown in barrier function or mere secondary manifestations to inflammation.
DOES THE CYTOSKELETON OF INTESTINAL EPITHHELIAL CELLS FUNCTION AS A CELLULAR ALARM TO IDENTIFY THE E. COLI INFECTION
Authors: Li Zhe , Elliott Elizabeth , Gunning Peter , O'Loughlin Edward
Published: January 2004

Intestinal epithelial cells play an important role in regulating host immunity in response to intestinal infection. Pathogenic bacteria (EPEC and EHEC) cause profound cytoskeletal rearrangement in intestinal epithelial cells during attachment or invasion. Rearrangement of cytoskeletal proteins could be a signal to up‐regulate host defence response.

Aims  To determine the role of actin cytoskeleton and microtubles in IL‐8 mRNA response to E. coli infection.

Methods  T84 cell monolayers in 6‐well plates were infected with HB101, EPEC and EHEC (105 CFU/well) and compared with uninfected control at 3, 6 and 12 h post infection. Control and infected monolayers were treated with nocodazole (Noc, microtubule disrupter, 30 mm), taxol (Tax, microtubule stabiliser, 10 mm), cytochalasin D (CytoD, actin depolymeriser, 100 nm) and Jasplakinolide (Jasp, actin polymeriser, stabilise actin filaments, 1 mm) and studied 6 h post infection. IL‐8 gene expression was measured by semiquantitative RT–PCR in control and uninfected monolayers with and without drug treatment and IL8 protein secretion by ELISA. The morphology of F‐actin and β‐tubulin was examined by FITC‐phaloidin staining (FAS), immunohistochemistry and confocal microscopy.

Results  IL‐8 mRNA and IL‐8 were increased by infection with all bacterial strains at 3 and 6 h but both IL‐8 mRNA and IL‐8 in EHEC and EPEC infection were decreased compared with control and HB101 at 12 h. Disruption of microfilaments by Noc increased IL‐8 (2.7 fold) while preservation of microfilaments by Tax inhibited IL8 response (0.5 fold) to HB101 infection only. CytoD decreased (0.1–0.5 fold) IL8 expression at all time points in all infections while stabilising actin by Jasp markedly increased the IL8 response (2–6 fold) in control, HB101, EHEC and EPEC at 3 and 6 h. CytoD inhibited Noc‐induced IL8 gene expression. Confocal microscopy demonstrated that CytoD and Noc caused major morphological damage to the actin and β‐tubulin by 6 h. Similar changes were also observed in EPEC and EHEC infection at 12 h but not HB101. Jasp preserved actin stress filaments in both EPEC and EHEC.

Conclusions  Disruption of microtubules and exogenous rearrangement of actin by pathogenic organism may be primary stimuli to up‐regulate proinflammatory cytokine gene expression. Preservation of actin filaments is required for this response and may be necessary for signal transduction to the nucleus.
DOSE‐DEPENDENT EFFECT OF LUMINAL BUTYRATE ON EPITHELIAL PROLIFERATION IN THE DISTAL COLON OF RATS
Authors: Sengupta S , Tjandra JJ , Gibson PR
Published: January 2004

Butyrate, a major product of bacterial fermentation of dietary fibre, is trophic to the colonic epithelium, when deprived of dietary fibre or faecal stream. However, the dose–response relationship of butyrate to this trophic effect is not known. The mechanism of this effect is still debated and how it relates to the antitumorigenic action of butyrate is unclear.

Aim  To characterise the dose–response relationship of the effect of butyrate delivered topically to the distal colon on fibre‐deprived atrophic colonic epithelium in rats.

Methods  Sixty‐four male Sprague–Dawley rats were maintained on a fibre‐free AIN 93G diet for 3 weeks to induce mucosal atrophy in the colon. The rats then underwent laparotomy for colonic intubation, in which a polyethylene tube was positioned at the proximal end of the distal colon via a caecotomy. After recovering from surgery, they were randomly divided into five groups, which were given for 4 days twice daily infusions of 0.5 mL butyrate at doses of 0, 10, 20, 40 or 80 mm (at which complete reversal of atrophy has been previously observed). Prior to sacrifice, the rats were injected intraperitoneally with vincristine to induce mitotic arrest. Crypt column heights and mitotic arrests were quantified by light microscopy.

Results  All treatment groups were healthy and stress‐free. The mucosa of vehicle‐infused rats was atrophic (mean 38 cells/crypt). Effects of twice daily infusions of butyrate were first observed on cell proliferation (number of mitotic arrests per crypt column) at 10 mm, and increased linearly to 80 mm. Crypt column height increased linearly from 20 mm to 80 mm, at which a mean of 45 cells/crypt were observed (the number usually observed in chow‐fed healthy rats). The mitotic index (number of mitotic arrests per 100 crypt cells) also increased linearly from 10 mm.

Conclusions  Butyrate's trophic effect showed a linear dose–dependent relationship. Although a maximal effect was not convincingly demonstrated, the results indicate that very small amounts of butyrate are required to affect epithelial proliferation. Since much higher luminal delivery is required to suppress tumorigenesis in this model, the mechanism by which butyrate exerts its trophic and antitumorigenic effects are likely to be different.
EFFECT OF PROBIOTICS ON TH1 and TH2 CYTOKINES: RELEVANCE TO PATHOGENESIS and TREATMENT OF ULCERATIVE COLITIS
Authors: Cayzer Catherine , Patel Kalpana , Wang Xin , Florin Timothy
Published: January 2004

Ulcerative colitis (UC) mucosa is associated with a cytokine imbalance with predominance of Th2 cytokines vs. Th1. A probiotic cocktail maintains remission in patients with pouchitis (Gionchetti, 2000). In addition, probiotics have similar efficacy to mesasal in maintaining remission in UC (Rembacken, 1999). This efficacy may be due to the ability of these organisms to modulate the immune response of the host. Mice fed Lactobacillus casei produce higher levels of the Th1 cytokines, IFNγ and IL‐2, and lower levels of the Th‐2 cytokines, IL‐4, IL‐5 and IL‐6 (Matsuzaki, 2000).

Hypothesis  Probiotocs may work in UC/pouchitis by up‐regulation of Th1 vs. Th2 cytokines to so restore immunological balance.

Study design  Five healthy, 5 UC, 5 CD subjects; not on immunosuppression. Trial two different probiotics (Lactobacillus paracasei LAFTI ™L26, and Bifidobacterium lactis LAFTI ™B94) sequentially and randomly with 2 weeks washout. Draw blood at time 0, 2 weeks post probiotic, 4 weeks (2 weeks post washout) and 6 weeks (2 weeks post second probiotic) for PBMC. Measure by ELISA cytokines in stimulated and unstimulated 44 h cultures. Stimulate PBMC with B94, L26, or other bacterial antigens.

Results  There are preliminary Th1 (TNFα, IFNγ) and Th2 (IL‐4, IL‐10) data for feeding B94, but TNFa data only for L26, for n = 2 healthy subjects. Baseline (0 week), for TNFa, unstimulated was 371 pg/mL and stimulated was for gram positive (gm+) antigens 2166 pg/mL and for gram negative (gm–) antigens 1022 pg/mL. For IFNγ, baseline stimulated and unstimulated levels were negligible. For IL‐4, baseline levels in unstimulated and stimulated cultures were low (< 100 pg/mL). With B94 (2 weeks), TNFα increased in both unstimulated (923 pg/mL) and stimulated PBMC, 4588 pg/mL (gm+), 3040 pg/mL (gm–), and significant IFNg was detected in gm+ stimulated cultures (> 1000 pg/mL), but not in unstimulated or gm– stimulated cultures. IL‐4 was down‐regulated to undetectable levels. Levels of IL‐10 varied. With L26 (week 6) there were increased levels of TNFα in unstimulated cultures (517 pg/mL) but decreased levels in stimulated cultures, 1751 pg/mL (gm +), 940 pg/mL (gm–).

Conclusion  The preliminary data for B94 but not L26 support the hypothesis that probiotics may prevent relapse of UC or pouchitis by effecting up‐regulation of Th1 vs. Th2 cytokines. The Gionchetti probiotic cocktail that was used to prevent pouchitis, contained both bifidobacteria and lactobacilli. It is not known which probiotic effected that treatment, but these preliminary data indicate probiotic effects on the immune system, which are diverse.
EPIDEMIOLOGY OF IRRITABLE BOWEL SYNDROME IN AN ASIAN URBAN SOCIETY
Authors: Gwee Kok Ann , Wai Chun Tao , Wong Mee Lian , Png Damian Cj
Published: January 2004

Background  Based on limited studies, it has been suggested that there is a lower prevalence of IBS among Asians and that there is male predominance in patients consulting for IBS. On the other hand, we have previously reported that in our hospital based clinic the prevalence and demography of IBS are similar to those of western series.

Aim  To study the epidemiology of IBS in an urban Asian population.

Method  A validated bowel symptom questionnaire was administered by trained interviewers first to a proportional age‐, sex‐ and race‐stratified random sample of 3000 residents in Singapore. IBS was defined using the Rome II criteria.

Results  In the community survey, the response rate was 78.2% (n = 2276, 1143 males and 1133 females). The age, sex and racial distribution of our respondents were similar to the general population and there was no significant difference between respondents and nonrespondents by type of household. The prevalence of IBS was 12.2%. The prevalence of IBS was higher in women than men (14.1 vs. 10.3%, P = 0.006), the younger age group (13.8% in those aged 40 years or less vs. 10.8% in those aged more than 40 years, P = 0.034). IBS subjects appeared to be more prone to abdominal surgery 7.2% IBS subjects vs. 2.9% non‐IBS subjects, P = 0.0004. The predominant bowel habits among community IBS subjects were constipation 47.1%, diarrhoea 44.4%. There was no difference in prevalence of IBS among different educational background.

Conclusion  The prevalence and demography of IBS in our Asian urban society is similar to the west with higher prevalence among women and younger age groups.
EPITHELIAL GROWTH OF THE SMALL INTESTINE OCCURS BY BOTH CRYPT FISSION and CRYPT HYPERPLASIA DURING INFANCY and CHILDHOOD IN HUMANS
Authors: Thompson FM , Couper RT , Davidson GP , Goland GJ , Moore DJ , Cummins AG
Published: January 2004

Our previous study has shown physiological crypt hyperplasia during infancy. Another mechanism of epithelial growth is crypt fission but this has not been investigated in humans. During crypt fission, crypts divide by unzipping from the base. A founder crypt divides into two daughter crypts with duplication of stem cells in the base. We investigated both crypt fission and crypt hyperplasia in infants (aged < 2 years, n = 4), children (aged 2–10 years, n = 7) and adults (n = 14) who had endoscopy for irritability/reflux oesophagitis in whom intestinal disease was unlikely. Duodenal biopsies were taken during endoscopy and villus area, crypt length, mitotic count per crypt and percentage of bifid crypts (a measure of crypt fission) were assessed by a microdissection technique. Villus area and crypt length correlate with villous and crypt enterocyte population, respectively. Mean ± SE villus area in infants, children and adults was 0.298 ± 0.009 mm2, 0.251 ± 0.029 mm2, and 0.257 ± 0.024 mm2, respectively, although no biopsies were available from neonates or infants < 6 months of age. Mean ± SE crypt length in infants, children, and adults was 284 ± 6, 299 ± 16 and 208 ± 13 μm, respectively. Mean ± SE mitotic count per crypt in infants, children and adults was 4.2 ± 0.1, 4.3 ± 0.8 and 2.1 ± 0.3, respectively. Thus, physiological crypt hyperplasia was present in both infants and children with longer crypts and higher proliferation of crypt cells. The mean ± SE percentage of bifid crypts in infants, children and adults was 9.1 ± 1.0, 5.0 ± 0.9 and 1.8 ± 0.5%, respectively. We conclude that crypt fission is predominantly elevated during infancy and to a lesser extent during childhood, whereas crypt hyperplasia is elevated equally during both infancy and childhood. We speculate this is due to differences in gene expression of positive and negative growth factors and their receptors.
EVALUATION OF IRRITABLE BOWEL SYNDROME USING ‘EXCLUSION CRITERIA’
Authors: Jafri Wasim , Jafri Nadim , Malooni Mahesh , Shah Hasnain , Hamid Saeed , Ahmed Ashfaq
Published: January 2004

Aims  To estimate the occurrence of IBS in patients who were evaluated for organic bowel problems in a tertiary care university hospital.

Methods  Seven hundred and seventy case records were retrieved from the medical records department who were evaluated for organic bowel problems. Data were fed into forms especially designed fulfilling the Manning and Rome 11 criteria for the diagnosis of IBS. Patients under went through history and physical along with comprehensive laboratory evaluation including CBC, ESR, LFTs, BUN, Creatinine, Electrolytes, Stool detailed report, Abdominal Ultrasound, Pelvic Ultrasound in females where indicated, Flexible sigmoidoscopy and or full colonoscopy, upper GI endoscopy, CT scan of the abdomen where indicated. ERCP was also performed in evaluation of cases in special circumstances.

Results  Seventy‐six patients (9.87%) fulfilled the diagnostic criteria for Irritable bowel syndrome. Abdominal pain was present in 75% of the cases, lower abdomen was the most frequent site in 68% of cases, and epigastric discomfort or pain was seen in 30%. Character of the pain was spasmodic in 50% of cases and the radiation was mostly to either side into the flanks. Pain and bloating were aggravated post–prandially. There was no special relationship to the type of food. Passage of flatus relieved bloating and pain in 30% of cases. Gas distribution was towards head in 8% and chest in 4% of cases. Stools were loose in 68% and hard, lumpy or straw shaped in the rest. Frequency of stooling was as low as 2/week to 10/day. Abdominal examination revealed epigastric tenderness in 14.7% and lower abdominal tenderness was found in 27.63%. Hemoglobin was normal in all except in 2 cases, which was due to excessive menstrual losses. ESR, LFTs, Bun, Creatinine, Electrolytes were normal in all cases. Stool detailed report was essentially normal in all, except cysts of Blastocystis Hominis were seen in 14% of cases. Flexible Sigmoidoscopy/and or Colonoscopy were normal in all cases except the presence of Hemorrhoids in 9%. Rectal biopsy was also normal in all cases. EGD revealed antral gastritis in 50% patients, which was positive for Helicobacter pylori in 62%. Anxiety and depression were significant in 28.9% of cases.

Conclusions  This study confirms that IBS is a common occurrence in a tertiary care Gastroenterology Center where mostly exclusion criteria is used for the diagnosis of IBS. This is to emphasize that the symptomatology of IBS is fairly consistent and characteristic and should be given weightage for the diagnosis of IBS. Exclusion criteria should be reserved for more difficult cases especially with the alarm symptoms.