Elemental diet as primary treatment of acute Crohn's disease: a controlled trial.

Acute exacerbations of Crohn''s disease are usually treated with prednisolone or potentially more toxic immunosuppressive drugs or by surgery. In pilot studies replacing the normal diet by a protein free elemental diet also induced remission. A controlled trial was therefore conducted in which 21 patients acutely ill with exacerbations of Crohn''s disease were randomised to receive either prednisolone 0.75 mg/kg/day or an elemental diet (Vivonex) for four weeks. Assessment at four and 12 weeks showed that the patients treated with the elemental diet had improved as much as and by some criteria more than the steroid treated group. Elemental diet is a safe and effective treatment for acute Crohn''s disease.     

Detection of inflammatory bowel disease in adults and children: evaluation of a new isotopic technique.

The distribution of radioactivity after the oral administration of sucralfate labelled with technetium-99m was studied in 33 patients with Crohn''s disease (13 adults, 20 children), 10 with ulcerative colitis (four adults), and 29 controls (23 with upper intestinal disease, four irritable bowel, one hypolactasia, and one malrotation of the gut). Positive scans were obtained in all patients with ulcerative colitis and 29 of 31 with active Crohn''s disease. The scans of two patients with inactive Crohn''s disease were negative. There were two false negative scans in patients with Crohn''s colitis and one false positive scan. Overall, sensitivity was 95% and specificity 97%. Comparison with radiology in 39 patients showed similar distribution of disease in 24 and more extensive disease in 12. The scan was inexpensive, simple to perform, well tolerated, allowed small and large bowel to be visualised simultaneously, and used a lower dose of radiation than barium studies. It may prove useful as a screening test for inflammatory bowel disease and in the serial assessment of disease activity.     

Diet and Crohn's disease: characteristics of the pre-illness diet.

Thirty newly diagnosed patients with Crohn''s disease were interviewed about their habitual, pre-illness diet and compared with 30 healthy controls, matched for age, sex, social class, and marital status. The patients ate substantially more refined sugar, slightly less dietary fibre, and considerably less raw fruit and vegetables than the controls. A diet high in refined sugar and low in raw fruit and vegetables precedes and may favour the development of Crohn''s disease.     

Elemental diets in treatment of acute Crohn's disease.

Twenty-seven patients with 32 acute exacerbations of Crohn''s disease were treated for four weeks with an elemental diet. At the end of treatment 29 of the exacerbations had remitted both clinically and biochemically. After six months six patients had relapsed. These findings suggest that the elemental diet is effective in treating acute Crohn''s disease, but the reasons are not clear. The diet may be effective because it provides nutritional support, is hypoallergenic, acts as a medical bypass from the affected area, or alters bowel flora. The patient''s general wellbeing is improved by the supply of adequate energy and essential foodstuffs in a form easily available without further digestion and given in a safe, simple, non-toxic way.     

Controlled multicentre therapeutic trial of an unrefined carbohydrate,fibre rich diet in Crohn's disease.

Between 1 September 1980 and 31 August 1983, 352 patients with inactive or mildly active Crohn''s disease but not taking drug treatment apart from sulphasalazine were entered from 40 hospitals into a prospective trial to assess the effects of two different diets on disease activity over two years. One hundred and sixty two patients were randomly allocated to take a diet unrestricted in sugar and low in fibre and 190 to a diet with little or no sugar and high in unrefined carbohydrate. No clear difference in clinical course was detected among patients who accepted the two different types of dietary advice.     

Crohn's disease of the appendix

Granulomatous inflammation typifying Crohn''s disease was centred within or confined to appendices in six patients, two of whom developed lesions attributable to Crohn''s disease elsewhere in the gut. The remaining four patients have remained symptom-free for periods varying from two to six years. Histological evidence of Crohn''s disease was also present in five of 46 appendices available for re-examination in a survey of 63 cases of Crohn''s enterocolitis. It is adduced that appendiceal involvement in Crohn''s disease is not uncommon.     

小肠CT及双气囊小肠镜诊断克罗恩病患者的差异性分析

目的:探究小肠CT及双气囊小肠镜诊断克罗恩病患者的差异性。方法:选择2017年4月至2019年3月于我院接受治疗的60例克罗恩病患者,分别实施小肠CT及双气囊小肠镜检测,对比两种检测方式对克罗恩病患者诊断准确率及病变范围、病变位置、活动度和并发症的检测差异。结果:CT检出克罗恩病的准确率96.67%,双气囊小肠镜检出克罗恩病的准确率为93.33%,其差异无统计学意义(P>0.05)。小肠CT主要表现为肠腔狭窄50例(83.33%),肠壁增厚52例(86.67%),肠外淋巴结46例(76.67%),肠系膜水肿及血管改变21例(35.00%),肠外炎症10例(16.67%),瘘管3例(5.00%),瘘道1例(1.67%);双气囊小肠镜表现为环形溃疡、不规则溃疡、环状溃疡等共计46例(76.67%),阿弗他溃疡22例(36.67%),黏膜充血、水肿等26例(43.33%),结节样增生6例(10.00%),小肠肠腔节段性狭窄16例(26.67%),假性息肉9例(15.00%);经病理学检测表现为淋巴细胞、中性粒细胞、嗜酸性粒细胞等炎性浸润,淋巴组织及肉芽组织出现增生小肠CT发现肠外炎症、瘘道、瘘管等合计14例,而双气囊小肠镜未发现并发症。结论:相比于双气囊小肠镜,小肠CT能够更为准确的判断克罗恩病患者是否处于炎症状态,也能够更有效的发现肠外并发症的存在,但小肠CT及双气囊小肠镜联合应用监测效果更佳。     

Immunoresponsiveness in Ulcerative Colitis and Crohn's Disease—Effect of Colectomy and Suppression of Disease Activity

We evaluated the effect of medically induced symptomatic disease improvement on in vitro tests of cell-mediated immune responses in 33 patients with Crohn''s disease. When results obtained in 17 patients with ulcerative colitis were compared with those of 10 patients with ulcerative colitis who had undergone a colectomy, no significant correlation was detected between individual clinical and laboratory variables or the Crohn''s disease activity index and in vitro tests of cell-mediated immunity. A different pattern emerged from the longitudinal tests of cell-mediated immunity: when these test results were initially abnormal in patients with Crohn''s disease, clinical improvement as assessed by the Crohn''s disease activity index was associated with normalizing cell-mediated immunity. In contrast, when the test results were initially normal, clinical improvement was not associated with any change in the immune response. Following colectomy in patients with ulcerative colitis, some abnormalities of suppressed immune responses remained, although patients were cured of their disease. Factors other than clinical disease activity may be responsible for the suppressed immunoresponsiveness in some patients with inflammatory bowel disease, and variable changes in cell-mediated immunity occur after both surgical and medical treatment.     

Effect of Crohn's disease mesenteric mesenchymal stem cells and their extracellular vesicles on T‐cell immunosuppressive capacity

Crohn''s disease (CD) is a chronic inflammatory disease of the gastrointestinal intestinal tract and has characteristic hypertrophic adipose changes observed in the mesentery. To better understand the role of the mesentery in the pathophysiology of Crohn''s disease (CD), we evaluated the immunomodulatory potential of mesenchymal stem cells (MSCs) and their secreted extracellular vesicles (EVs) derived from Crohn''s patients. MSCs and EVs were isolated from the mesentery and subcutaneous tissues of CD patients and healthy individuals subcutaneous tissues, and were analysed for differentiation, cytokine expression, self‐renewal and proliferation. The varying capacity of these tissue‐derived MSCs and EVs to attenuate T‐cell activation was measured in in vitro and an in vivo murine model. RNA sequencing of inflamed Crohn''s disease mesentery tissue revealed an enrichment of T‐cell activation compared to non‐inflamed subcutaneous tissue. MSCs and MSC‐derived EVs isolated from Crohn''s mesentery lose their ability to attenuate DSS‐induced colitis compared to subcutaneous tissue‐derived cell or EV therapy. We found that treatment with subcutaneous isolated MSCs and their EV product compared to Crohn''s mesentery MSCs or EVs, the inhibition of T‐cell proliferation and IFN‐γ, IL‐17a production increased, suggesting a non‐inflamed microenvironment allows for T‐cell inhibition by MSCs/EVs. Our results demonstrate that Crohn''s patient‐derived diseased mesentery tissue MSCs lose their immunosuppressive capacity in the treatment of colitis by distinct regulation of pathogenic T‐cell responses and/or T‐cell infiltration into the colon.     

Adhesive Escherichia coli in inflammatory bowel disease and infective diarrhoea.

The clinical features of ulcerative colitis and Crohn''s disease are similar to those of infections of the bowel, although their cause is uncertain. Many bacteria that cause intestinal diseases adhere to the gut mucosa, and adhesion of pathogenic Escherichia coli is resistant to D-mannose. The adhesive properties of isolates of E coli were assessed by assay of adhesion to buccal epithelial cells with mannose added. The isolates were obtained from patients with inflammatory bowel diseases (50 with a relapse of ulcerative colitis, nine with ulcerative colitis in remission, 13 with Crohn''s disease, and 11 with infectious diarrhoea not due to E coli) and 22 controls. The median index of adhesion to buccal epithelial cells (the proportion of cells with more than 50 adherent bacteria) for E coli from patients with ulcerative colitis in relapse was significantly higher (43%) than that for controls (5%) and patients with infectious diarrhoea (14%). The index was not significantly different among isolates from patients with ulcerative colitis in relapse, Crohn''s disease (53%), and ulcerative colitis in remission (30%). If an index of adhesion of greater than 25% is taken as indicating an adhesive strain 86% of isolates of E coli from patients with inflammatory bowel disease were adhesive compared with 27% from patients with infective diarrhoea and none from controls. The adhesive properties of the isolates from patients with inflammatory bowel disease were similar to those of pathogenic intestinal E coli, raising the possibility that they may have a role in the pathogenesis of the condition; the smaller proportion of adhesive isolates in patients with infective diarrhoea due to other bacteria suggests that the organism may be of primary importance rather than arising secondarily.     

Prioritisation and Network Analysis of Crohn's Disease Susceptibility Genes

Recent Genome-Wide Association Studies (GWAS) have revealed numerous Crohn''s disease susceptibility genes and a key challenge now is in understanding how risk polymorphisms in associated genes might contribute to development of this disease. For a gene to contribute to disease phenotype, its risk variant will likely adversely communicate with a variety of other gene products to result in dysregulation of common signaling pathways. A vital challenge is to elucidate pathways of potentially greatest influence on pathological behaviour, in a manner recognizing how multiple relevant genes may yield integrative effect. In this work we apply mathematical analysis of networks involving the list of recently described Crohn''s susceptibility genes, to prioritise pathways in relation to their potential development of this disease. Prioritisation was performed by applying a text mining and a diffusion based method (GRAIL, GPEC). Prospective biological significance of the resulting prioritised list of proteins is highlighted by changes in their gene expression levels in Crohn''s patients intestinal tissue in comparison with healthy donors.     

In-vitro Inhibition of Leucocyte Migration in Crohn's Disease by a Sarcoid Spleen Suspension

A Kveim suspension has been shown to inhibit the migration of leucocytes in vitro from 12 out of 18 patients with Crohn''s disease but to have no comparable effect on leucocytes from patients with ulcerative colitis or from a group of patients with other diseases. These findings provide further evidence of cross-reactivity or of a possible aetiological link between Crohn''s disease and sarcoidosis and suggest a further immunological distinction between Crohn''s disease and ulcerative colitis.     

Association of IRGM Gene Mutations with Inflammatory Bowel Disease in the Indian Population

Background

Mutations in the IRGM gene have been associated with Crohn''s disease in several populations but have not been explored in Indian patients with this disease. This study examined the association of IRGM mutations with ulcerative colitis and Crohn''s disease in Indian patients with inflammatory bowel disease.

Methods

The IRGM gene was amplified in four segments and Sanger-sequenced in 101 participants (42 Crohn''s disease, 39 ulcerative colitis, and 20 healthy controls). Ten single nucleotide polymorphisms (SNP) were genotyped in 1200 participants (352 Crohn''s disease, 400 ulcerative colitis, and 448 healthy controls) using Sequenom MassARRAY iPLEX. Disease associations were evaluated for each of the ten SNPs.

Results

Thirty one mutations were identified in the IRGM gene, of which two had not hitherto been reported (150226250- ss947429272 & 150227858- ss947429273). Ten SNPs (6 from the above and 4 from the literature) were evaluated. Significant associations with Crohn''s disease were noted with the T allele of rs1000113 (OR 1.46, 95% CI 1.12–1.90), T allele of rs9637876 (OR 1.25, 95% CI 1.005–1.561) and C allele of rs 13361189 (OR 1.33, 95% CI 1.07–1.669). Two SNPs – rs11747270 and rs180802994 – did not exhibit Hardy-Weinberg equilibrium but were associated with both Crohn''s disease and ulcerative colitis in this population. The remaining SNPs did not show significant associations with either Crohn''s disease or ulcerative colitis.

Conclusions

Association of IRGM gene SNPs with Crohn''s disease is reported for the first time in Indian patients. We also report, for the first time, an association of rs 9637876 in the IRGM gene with Crohn''s disease.     

Probiotics modulate intestinal expression of nuclear receptor and provide counter-regulatory signals to inflammation-driven adipose tissue activation

Background

Adipocytes from mesenteric white adipose tissue amplify the inflammatory response and participate in inflammation-driven immune dysfunction in Crohn''s disease by releasing proinflammatory mediators. Peroxisome proliferator-activated receptors (PPAR)-α and -γ, pregnane x receptor (PXR), farnesoid x receptor (FXR) and liver x-receptor (LXR) are ligand-activated nuclear receptor that provide counter-regulatory signals to dysregulated immunity and modulates adipose tissue.

Aims

To investigate the expression and function of nuclear receptors in intestinal and adipose tissues in a rodent model of colitis and mesenteric fat from Crohn''s patients and to investigate their modulation by probiotics.

Methods

Colitis was induced by TNBS administration. Mice were administered vehicle or VSL#3, daily for 10 days. Abdominal fat explants obtained at surgery from five Crohn''s disease patients and five patients with colon cancer were cultured with VSL#3 medium.

Results

Probiotic administration attenuated development of signs and symptoms of colitis, reduced colonic expression of TNFα, IL-6 and IFNγ and reserved colonic downregulation of PPARγ, PXR and FXR caused by TNBS. Mesenteric fat depots isolated from TNBS-treated animals had increased expression of inflammatory mediators along with PPARγ, FXR, leptin and adiponectin. These changes were prevented by VSL#3. Creeping fat and mesenteric adipose tissue from Crohn''s patients showed a differential expression of PPARγ and FXR with both tissue expressing high levels of leptin. Exposure of these tissues to VSL#3 medium abrogates leptin release.

Conclusions

Mesenteric adipose tissue from rodent colitis and Crohn''s disease is metabolically active and shows inflammation-driven regulation of PPARγ, FXR and leptin. Probiotics correct the inflammation-driven metabolic dysfunction.     

Juvenile onset inflammatory bowel disease: height and body mass index in adult life.

OBJECTIVE--To establish the frequency of permanent growth failure in juvenile onset inflammatory bowel disease. DESIGN--Measurement of height and weight in a geographically based cohort at a mean of 14 (range 5.2-29.5) years after diagnosis. Comparison with data from surveys of British adults in 1980 and 1987. SETTING--NHS hospitals throughout Scotland. SUBJECTS--105 Children admitted to hospital during 1968-83 who fulfilled diagnostic criteria for Crohn''s disease or ulcerative colitis and lived in specified regions. 87 were aged over 18 and living in Britain at follow up. MAIN OUTCOME MEASURES--Height, weight, body mass index, and sexual maturity. RESULTS--All patients were sexually mature. 67 of the 70 patients examined were of normal height, and three women with Crohn''s disease were abnormally short. Weight and body mass index were normal in all patients with ulcerative colitis. Patients with Crohn''s disease had significantly lower weight than those with ulcerative colitis (men 66.8 (9.5) kg v 78.4 (13.8) kg, P = 0.04; women 51.5 (8.2) kg v 63.0 (12.1) kg, P < 0.02) irrespective of disease activity. Body mass index was also significantly lower than the normal distribution (P < 0.01). Growth retardation was not mentioned as a problem for any of the 17 patients interviewed only by telephone. CONCLUSIONS--Despite growth retardation in the teenage years most young people with inflammatory bowel disease will eventually achieve normal height. Reasons for lower weight in patients with Crohn''s disease remain to be established.     

IDO1 and IDO2 Non-Synonymous Gene Variants: Correlation with Crohn's Disease Risk and Clinical Phenotype

BackgroundCrohn''s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Genetic polymorphisms can confer CD risk and influence disease phenotype. Indoleamine 2,3 dioxygenase-1 (IDO1) is one of the most over-expressed genes in CD and mediates potent anti-inflammatory effects via tryptophan metabolism along the kynurenine pathway. We aimed to determine whether non-synonymous polymorphisms in IDO1 or IDO2 (a gene paralog) are important either as CD risk alleles or as modifiers of CD phenotype.MethodsUtilizing a prospectively collected database, clinically phenotyped CD patients (n = 734) and non-IBD controls (n = 354) were genotyped for established IDO1 and IDO2 non-synonymous single nucleotide polymorphisms (SNPs) and novel genetic variants elucidated in the literature. Allelic frequencies between CD and non-IBD controls were compared. Genotype-phenotype analysis was conducted. IDO1 enzyme activity was assessed by calculating the serum kynurenine to tryptophan ratio (K/T).ResultsIDO1 SNPs were rare (1.7% non-IBD vs 1.1% CD; p = NS) and not linked to Crohn''s disease diagnosis in this population. IDO1 SNPs did however associate with a severe clinical course, presence of perianal disease, extraintestinal manifestations and a reduced serum K/T ratio during active disease suggesting lower IDO1 function. IDO2 minor allele variants were common and one of them, rs45003083, associated with reduced risk of Crohn''s disease (p = 0.025). No IDO2 SNPs associated with a particular Crohn''s disease clinical phenotype.ConclusionsThis work highlights the functional importance of IDO enzymes in human Crohn''s disease and establishes relative rates of IDO genetic variants in a US population.     

Intestinal permeability in children with Crohn's disease and coeliac disease.

Mannitol and lactulose were used as probe molecules to measure intestinal permeability in children with active small-bowel Crohn''s disease and with untreated coeliac disease. Mannitol and lactulose were administered by mouth in a moderately hypertonic solution (580 mmol (mosmol)/l), and results were expressed as the ratio of the molecules excreted in urine over five hours. Patients with Crohn''s disease had a sixfold increase in permeability (due to increased lactulose permeability) and those with coeliac disease a fivefold increase (due to decreased mannitol permeability). From these results the test offers potential as a noninvasive investigation in children with small-bowel disease.     

Crohn's Disease and Pregnancy

This paper reports the outcome of 60 pregnancies in 40 women, all of whom had concomitant Crohn''s disease. Detailed analysis of pregnancy rates in Crohn''s disease supports in outline the hypothesis that some patients with bowel symptoms may be rendered temporarily subfertile by the activity of their bowel complaints. In contrast there is little or no evidence of any adverse effect during pregnancy on mother or child. Most pregnancies went normally to term and, if anything, Crohn''s disease tended to improve during the period of confinement.After delivery, however, over 40% of patients suffered a relapse of Crohn''s disease. Such a situation might well constitute a logical indication for the administration of corticosteroid therapy.     

Finger clubbing in inflammatory bowel disease: its prevalence and pathogenesis.

Finger clubbing, measured objectively by using the hyponychial angle, was present in 75 out of 200 (38%) patients with Crohn''s disease, 15 out of 103 (15%) with ulcerative colitis, and two out of 24 (8%) with proctitis. In Crohn''s disease and ulcerative colitis the hyponychial angle was significantly correlated with both disease activity and the extent of fibrosis in the resected specimens from 47 surgically treated patients. The prevalence of finger clubbing in patients with macroscopic disease within the area of the gut innervated by the vagus nerve was significantly higher than that in patients in whom the disease was confined to the distal colon and rectum. Finger clubbing in patients with Crohn''s disease tended to regress after resection of macroscopic disease. It is concluded that finger clubbing is significantly commoner in Crohn''s disease than ulcerative colitis. The focal stimuli for finger clubbing include mucosal inflammatory change and fibrosis mediated by the vagus and possibly other autonomic pathways acting as the afferent arc of a finger-clubbing reflex.     

Investigation of inheritance of chronic inflammatory bowel diseases by complex segregation analysis.

OBJECTIVE--To investigate the mode of inheritance of ulcerative colitis and Crohn''s disease by complex segregation analysis. DESIGN--Cross sectional population based survey of familial occurrence of chronic inflammatory bowel disease. SETTING--Population of the Copenhagen county in 1987. SUBJECTS--662 patients in whom inflammatory bowel disease had been diagnosed before 1979, of whom 637 (96%) provided adequate information. Of 504 patients with ulcerative colitis, 54 had 77 relatives with ulcerative colitis and of 133 patients with Crohn''s disease, five had seven relatives with Crohn''s disease. MAIN OUTCOME MEASURES--Patterns of segregation of either disease as assessed by complex segregation analysis performed with the computer program POINTER. RESULTS--The analysis suggested that a major dominant gene with a penetrance of 0.20-0.26 is present in 9-13% of adult patients with ulcerative colitis. The analysis did not allow for other components in the familial aggregation. For Crohn''s disease the best fitting model included a major recessive gene with complete penetrance, for which 7% of the patients are homozygous. However, this model was not significantly different from a multifactorial model. CONCLUSIONS--The segregation pattern indicates that a major dominant gene has a role in ulcerative colitis, and suggests that a major recessive gene has a role in Crohn''s disease.