Spectrum Of Inflammatory Bowel Disease Research Articles

The highly stabilized biologically derived peptide VIESPPEI alleviates DSS-induced colitis in mice by preventing colonic atrophy and modulating gut microbiota

Ulcerative colitis (UC) is a recurrent gastrointestinal infection within the spectrum of inflammatory bowel disease, posing risks associated with long-term medication. Consequently, this study aimed to investigate the effects of novel duck liver protein-derived bioactive peptides, characterized by a higher safety profile, on dextran sulfate sodium (DSS)-induced colitis in mice. The results indicated that the retention rate of VIESPPEI remained above 80% following simulated gastrointestinal digestion in vitro, demonstrating strong stability and practical application potential. The peptide VIESPPEI was found to alleviate weight loss in colitis-afflicted mice, inhibit the elevation of the disease activity index (DAI), and significantly improve symptoms such as atrophy and shortening of the colon. Histological examination further confirmed that VIESPPEI intake promoted the recovery of acute colitis in mice. Additionally, it significantly reduced myeloperoxidase activity and increased superoxide dismutase and catalase activities in the colon tissues of UC mice. Notably, a substantial increase in beneficial gut microbiota and the populations of three beneficial bacteria species (Anaplasma spp., Tannabacterium spp., and Bifidobacterium spp.) that produce short-chain fatty acids, along with a decrease in pathogenic groups such as Streptococcus and Turicibacter, may account for the improvement in colitis observed in UC mice treated with VIESPPEI. This study provides new evidence that VIESPPEI alleviates UC and provides a theoretical basis for the development of functional peptide beverages.

Harnessing the Power of Precision Medicine and Novel Biomarkers to Treat Crohn’s Disease

Crohn's disease (CD) is a chronic inflammatory condition that affects the gastrointestinal tract. It is part of a spectrum of inflammatory Bowel Diseases (IBD). The disease is complex, characterized by significant inter and intra-individual heterogeneity, which contributes to a diverse and multifaceted portrayal of the disease. Consequently, applying specific and accurate treatment is challenging, and therapeutic success rates remain disappointing and insufficient. In recent years, significant advances in the therapeutic potential of CD have been made. Hope has been provided by these developments in the form of an expanding treatment toolkit. However, even with these beneficial adjustments, patients are frequently treated using an ineffective "one size fits all" treatment protocol, ultimately leading to a plateau in drug effectiveness and a decline in overall treatment success rates. Furthermore, with the advancement in the genome-wide association study, in combination with significant bioinformatic developments, the world of medicine has moved in the direction of personalized, tailored-treatment medicine, and this trend has not escaped the world of IBDs. Prediction models, novel biomarkers, and complex algorithms are emerging and inspiring optimism that CD patients will be treated with "precision medicine" in the near future, meaning that their treatments will be selected based on the patient's various unique features. In this review, we will outline the current diagnostic and therapeutic limitations that lead to a glass ceiling effect and thus send us in pursuit of discovering novel biomarkers. We will illustrate the challenges and difficulties in discovering relevant and innovative biomarkers and implementing them into everyday clinical practice. We will also heighten the progress made in practicing personalized medicine for CD patients and shed light on future directions and horizons.

The metabolic nature of inflammatory bowel diseases.

Crohn's disease and ulcerative colitis, phenotypically comprising a spectrum of inflammatory bowel diseases (IBDs), spread globally during the westernization of lifestyle and dietary habits over the past few decades. Here, we review experimental and clinical evidence for the metabolic nature of gut inflammation in IBD and delineate distinct parallels to the inflammatory state in metabolic diseases. Experimental evidence indicates that excessive intake of specific macronutrients in a Western diet fuels an inflammatory response in the gut by exploiting sensors of innate immunity and perturbation of gut microbial metabolism. Genetic IBD risk partly affects metabolism and stress signalling of innate immunity, and immunometabolism controls susceptibility to gut inflammation. Epidemiological and clinical studies indicate that specific nutrients in the Western diet pose a risk for the development of IBD and a poor disease course. Translational studies in IBD indicate perturbation of energy metabolism in immune cells and perturbation of gut microbial metabolism, which can be shaped by diet. In turn, dietary restriction by exclusive enteral nutrition induces remission in patients with IBD. Collectively, these studies support a metabolic underpinning of gut inflammation in IBD as described for metabolic inflammation in obesity and related disorders.

Controversies in Crohn's Disease Before and After Pouch Surgery.

IPAA is rarely performed in patients with a known diagnosis of Crohn's disease, although it may be done in highly selected patients with an absence of perianal disease or small bowel inflammation. Patients with a preoperative diagnosis of Crohn's disease are, however, at increased risk of developing Crohn's disease of the pouch. Crohn's disease of the pouch can also occur in people with a preoperative diagnosis of ulcerative colitis; however, it is unknown whether this phenotype is similar to classic Crohn's disease involving an intact bowel, or whether it is a distinct entity. This study aimed to describe Crohn's disease of the pouch, including luminal inflammation, and fibrostenotic and perforating phenotypes, as well as management of these conditions. Crohn's disease of the pouch can present in similar ways as classic Crohn's disease, classified as either inflammatory, fibrostenotic, or penetrating. Criteria involving the diagnosis of Crohn's disease of the pouch are stringent to prevent unnecessary treatments, because a diagnosis of Crohn's disease after IPAA for presumed ulcerative colitis can cause mental anguish. Treatment of Crohn's disease of the pouch depends on the presenting phenotype, although therapies are similar to classic Crohn's disease. Endoscopic, or even surgical treatment, may be required for fibrostenotic and fistulizing diseases. Crohn's disease of the pouch is a newly described disease of patients who undergo an ileoanal pouch anastomosis; and therefore, most of the evidence comes from retrospective trials in patients with an initial diagnosis of ulcerative colitis. While Crohn's disease of the pouch is controversial and perhaps a distinct disease within the spectrum of inflammatory bowel diseases, it nonetheless requires long-term medical therapy and close follow-up.

MICROSCOPIC COLITIS IS ASSOCIATED WITH DECREASED BONE DENSITY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract INTRODUCTION Although, microscopic colitis (MC) can be considered as spectrum of inflammatory bowel disease (IBD), MC is very different in many aspects; in terms of risk factors, symptoms, course of disease, treatment, and complication. Low bone mineral density (BMD) is previously known as complication of IBD. There are few data about MC and risk of bone density loss. We conduct this systematic review and meta-analysis to determine the association between MC and low BMD. METHODS A comprehensive literature review was conducted using the MEDLINE, and EMBASE databases through October 2021 to identify studies that demonstrated association between clinical outcomes of interest, MC and low BMD. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS After two rounds of review, four studies met our eligibility criteria and were included in analysis. The result showed statistically significant association between MC and low bone density (pooled OR = 2.15, 95% CI: 1.06 - 4.38, p = 0.03) The forest plots and funnel plots are shown below. CONCLUSIONS Our meta-analysis found significant association between MC and low bone density. Therefore, this data may suggest that BMD screening could be applied for MC patients, and such patients may have benefit from calcium and vitamin D supplementation. Further studies should be done to determine the significance of this issue.

MICROSCOPIC COLITIS IS ASSOCIATED WITH DECREASED BONE DENSITY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Although, microscopic colitis (MC) can be considered as spectrum of inflammatory bowel disease (IBD), MC is very different in many aspects; in terms of risk factors, symptoms, course of disease, treatment, and complication. Low bone mineral density (BMD) is previously known as complication of IBD. There are few data about MC and risk of bone density loss. We conduct this systematic review and meta-analysis to determine the association between MC and low BMD.

DOP78 The differential diagnosis and clinicopathological spectrum of Inflammatory Bowel Disease: An interesting and informative ECCO topical review

Abstract Background A wide variety of intestinal and non-intestinal diseases can resemble chronic idiopathic inflammatory bowel disease (IBD) clinically and/or pathologically. The aim of the current Topical Review was to explore the differential diagnosis of IBD and to discuss clinical, histomorphological features and ancillary techniques that help distinguish between IBD and its mimics. Methods An open ECCO call led to the selection of 12 participants who formed three working groups (WG) to study the mimics of IBD. WG 1 comprised gastroenterologists, who explored mainly the clinical features. WG 2 consisted of histopathologists, who focused on macroscopic and microscopic pathological aspects. WG 3 was a mixed group of pathologists and clinicians who studied the value of additional investigative techniques such as imaging, serology and molecular markers. A systematic literature search allowed exploration of these topics and the identification of the most helpful and relevant distinguishing features. The process led to the development of Current Practice Position (CPP) statements and supporting text. Consensus meetings with voting by all participants facilitated modification and finalisation of CPP statements. Results The project highlighted several points. Firstly, there is a wide and sometimes overwhelming variety of potential mimics of new and established IBD, both in adults and in children. Secondly, some mimics are more important clinically and others pathologically, meaning that the emphasis on the mimics of IBD is different for clinicians and pathologists. Thirdly, close attention to all clinical features, pathological findings and other evidence optimises accuracy. Finally, newer techniques sometimes have a role, e.g., in distinguishing monogenic IBD-like disorders from IBD in young children, and the value of many novel techniques is as yet uncertain. A practical message is that constant awareness by clinicians and pathologists of the possibility of mimics is particularly important. Conclusion Discussions between pathologists and clinicians were particularly useful during this process and were a reminder of the importance of clinicopathological correlation. There is a wide variety of mimics of IBD, including infections, diverticular disease, drug effect, radiation damage, immune disorders, vascular disorders and diversion proctocolitis. An important, relatively new, and sometimes very close mimic of IBD is immune checkpoint inhibitor colitis. In turn, reliable distinction between IBD and other entities requires a multidisciplinary approach with a full clinical history (including duration of disease), and with appropriate investigations that may include endoscopy, pathology, imaging, microbiological tests, serology, and newer molecular tests.

To Study of Spectrum of Inflammatory Bowel Disease in Western Rajasthan

To Study of Spectrum of Inflammatory Bowel Disease in Western Rajasthan

Considerations and Changes in the Evaluation, Management, and Outcomes in the Management of Diverticular Disease: The Diagnosis, Pathology, and Treatment of Diverticular Colitis.

Diverticular colitis, also known as segmental colitis associated with diverticulosis, is a colonic inflammatory disorder on the spectrum of inflammatory bowel disease (IBD). The disease consists of macroscopic and microscopic inflammation affecting inter-diverticular mucosa, sparing peri-diverticular mucosa, with inflammation confined to the descending and sigmoid colon. The disease likely arises from the altered immune response of an individual, genetically susceptible to the IBD spectrum of diseases. Patients with segmental colitis associated with diverticulosis (SCAD) are typically older, and likely represent a subgroup of IBD-susceptible patients who lacked an environmental trigger until that point in their life. Most patients remain in remission with initial treatments of mesalamine or topical steroids, and maintenance mesalamine afterwards. Only the most severe form of the disease necessitates immunomodulatory therapy and the consideration of surgery.

Investigation of val109/asp polymorphism of omentin gene in ulcerative colitis patients

Autoimmune diseases are a large complex group of diseases, where both genes and environment contribute to disease development. Ulcerative colitis (UC) is an autoimmune disease of unknown etiology belongs to the spectrum of inflammatory bowel diseases (IBD). UC is a heterogeneous disease of which several genes have been involved in the pathogenesis. Omentin, is a newly discovered cytokine, has 8 exons and 7 introns it is located on chromosome 1 q22-23. Omentin acts as an anti-inflammatory cytokine and the association between omentin and several inflammatory diseases such as (type2 diabetes, asthma, rheumatoid arthritis, psoriasis) has been investigated. In this study we aimed to investigate putative relationship between SNP (Single Nucleotide Polymorphism) in omentin gene and ulcerative colitis disease by using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Val109/Asp (rs2274907) polymorphism is a missense mutation (nonsynonymous substitution) located in exon 4 of the omentin gene. For this aim, 39 patients diagnosed with UC and 31 cases (control) with no diagnosis of UC for were used. Both groups were at a similar range of age and gender enrolled in our study. According to chi-square test run on the data, there was no significant correlation between the genotypes studied and the status of the disease (p=0.652). However, when odd ratios (OR) were calculated, it was determined that TT genotype was observed in patients as 4.35 times higher as observed in the control group. Many other studies are needed to demonstrate the real putative relationship between Single Nucleotide Polymorphism in omentin gene and ulcerative colitis.

Psoriasis and inflammatory bowel disease: links and risks.

Psoriasis and the spectrum of inflammatory bowel diseases (IBD) are chronic, inflammatory, organotropic conditions. The epidemiologic coexistence of these diseases is corroborated by findings at the level of disease, biogeography, and intrafamilial and intrapatient coincidence. The identification of shared susceptibility loci and DNA polymorphisms has confirmed this correlation at a genetic level. The pathogenesis of both diseases implicates the innate and adaptive segments of the immune system. Increased permeability of the epidermal barrier in skin and intestine underlies the augmented interaction of allergens and pathogens with inflammatory receptors of immune cells. The immune response between psoriasis and IBD is similar and comprises phagocytic, dendritic, and natural killer cell, along with a milieu of cytokines and antimicrobial peptides that stimulate T-cells. The interplay between dendritic cells and Th17 cells appears to be the core dysregulated immune pathway in all these conditions. The distinct similarities in the pathogenesis are also reflected in the wide overlapping of their therapeutic approaches. Small-molecule pharmacologic immunomodulators have been applied, and more recently, biologic treatments that target proinflammatory interleukins have been introduced or are currently being evaluated. However, the fact that some treatments are quite selective for either skin or gut conditions also highlights their crucial pathophysiologic differences. In the present review, a comprehensive comparison of risk factors, pathogenesis links, and therapeutic strategies for psoriasis and IBD is presented. Specific emphasis is placed on the role of the immune cell species and inflammatory mediators participating in the pathogenesis of these diseases.

Collagenous Colitis and Inflammatory Bowel Disease: Is It a Complication or Spectrum of the Same Disease?

Purpose: Collagenous colitis is an inflammatory mucosal disorder that results in chronic watery diarrhea without bleeding. It is characterized by a thick subepithelial collagen band and increased lymphocytes in the lamina propria of an otherwise endoscopically normal-appearing colon. It is generally benign disease, with a course that is characterized by alternating spontaneous relapses and remissions. There have been cases reported in literature in which microscopic colitis preceded Crohn's disease and ulcerative colitis. It is unclear to date if these cases are only coincidental or represent progression of disease. We report one patient who was diagnosed with collagenous colitis 2 years ago. His prior treatment included budesonide and cholestyramine intermittently. The patient presented with severe abdominal pain, weight loss, anorexia, and bloody diarrhea. Colonoscopy showed mucosal changes suggestive of ulcerative colitis; diagnosis was confirmed with biopsy interpretation. Stool studies were negative. The patient was started on intravenous solu-medrol. His symptoms improved for a few days but then again progressed to severe bloody diarrhea with abdominal pain. A flexible sigmoidoscopy was performed revealing persistent inflammatory mucosal changes. Biopsies also showed cytomegalovirus in the background of ulcerative colitis. Intravenous gancyclovir therapy was added to the medical regimen. Patient's symptoms resolved within a week and the patient was discharged home on valgancyclovir and prednisone. We report an additional case report, added to the previous six, which augments the theory that collagenous colitis could be a part of the spectrum of inflammatory bowel disease (Table 1).Table 1: Reported cases of collagenous colitis evolving into ulcerative colitis

Microscopic colitis: Is it a spectrum of inflammatory bowel disease?

Lymphocytic and collagenous colitis are forms of microscopic colitis which typically presents in elderly patients as chronic watery diarrhea. The association between microscopic colitis and inflammatory bowel disease is weak and unclear. Lymphocytic colitis progressing to ulcerative colitis has been previously reported; however there is limited data on ulcerative colitis evolving into microscopic (lymphocytic or collagenous) colitis. We report a series of six patients with documented ulcerative colitis who subsequently were diagnosed with collagenous colitis or lymphocytic colitis suggesting microscopic colitis could be a part of the spectrum of inflammatory bowel disease. The median duration of ulcerative colitis prior to being diagnosed with microscopic colitis was 15 years. We noted complete histological and/or symptomatic remission in three out of six cases while the other three patients reverted back into ulcerative colitis suggesting lymphocytic or collagenous colitis could present as a continuum of ulcerative colitis. The exact molecular mechanism of this histological transformation or the prognostic implications is still unclear. Till then it might be prudent to follow up these patients to assess for the relapse of inflammatory bowel disease as well as for dysplasia surveillance.

Lymphocytic Colitis: A Spectrum of Inflammatory Bowel Disease: A Case Series

Introduction: Lymphocytic colitis (LC) is characterized by chronic diarrhea and specific microscopic changes in a macroscopically normal colonic mucosa. Lymphocytic colitis progressing to ulcerative colitis (UC) has been previously reported, however there is limited data on UC evolving into LC. Here we present a series of five cases with UC subsequently developing into lymphocytic colitis suggesting LC could be a part of the spectrum of inflammatory bowel disease (IBD). Case Report: A total of five cases of UC evolving into LC were identified using a retrospective database study of 876 UC patients diagnosed during years 2001-2011 at the Cleveland Clinic. The median age at the time of UC diagnosis was 34 years. All five patients had a chronic history of UC for a median duration of 15 years prior to being diagnosed with LC by histopathology. Three out of five patients were on treatment for UC with either mesalamine or salfasalazine and the other two patients were treated with either prednisone, mesalamine or 6-mercaptopurine at the time of diagnosis of LC. All patients were under complete remission with medications. On subsequent follow up three out of five people relapsed with intermittent watery diarrhea prompting a colonoscopy which suggested no evidence of active UC but had histological pattern of LC on their random mucosal biopsies. The other two patients were asymptomatic from UC and had evidence of LC during routine surveillance colonoscopic biopsies. Discussion: Lymphocytic colitis, a subtype of microscopic colitis, with chronic inflammatory infiltrates in the colonic mucosa without specific abnormalities noted on endoscopy. We found five patients with longstanding UC who subsequently developed LC. We noted complete histological and/or symptomatic remission in three out of the five cases while two of these patients reverted back into ulcerative colitis suggesting that LC could present as a continuum of UC. There have been case reports of collagenous colitis evolving into ulcerative colitis and vice versa. Literature reveals NF- kB activation occurs early in both collagenous colitis and ulcerative colitis but downstream cellular programs appear different in both. However, in LC the exact molecular mechanism of this histological transformation or the prognostic implications is lacking and requires further evaluation on prospective studies. Until then, it might be prudent to follow up these patients with LC to assess for relapse of UC. We therefore suggest lymphocytic colitis could be part of the spectrum of inflammatory bowel disease.Table: [1160] Cases of ulcerative colitis subsequently developing lymphocytic colitis

Improvement of Cardiomyopathy after Infliximab Treatment for Crohnʼs Disease (CD)

Rare instantes for cardiovascular complications of Inflammatory Bowel Disease have been reported, including valvular insufficiency, conduction disorders, pericarditis, myocarditis, pericardial tamponade, dilated cardiomyopathies (DCM) and endomyocardial fibrosis. Caution has been advised when using infliximab (INF) in patients with heart disease, especially DCM, because of an increased risk of sudden death. We report a 17 y/o male with CD diagnosed at 9 yrs age, when he presented bloody diarrhea, weight loss and abdominal pain. He had many hospitalizations for exacerbations and perianal fistulizing disease treated with courses of steroids and 5-ASA. In 2004, progressive shortness of breath leading to mechanical ventilation prompted a diagnosis of DCM, with ejection fraction (EF) of 22%. Treatment with carvelidol and ACE inhibitors stabilized his heart disease. In 2005, he developed a retroperitoneal abscess requiring drainage and antibiotics. An colocutaneous fistula required a segmental colectomy with end colostomy and mucous fistula. In early 2006, he presented with an acute abdomen. Exploratory revealed a jejunal volvulus with necrosis and severe colonic disease, requiring segmental small bowel resection, subtotal colectomy and end ileostomy. Because of the aggressive disease, infliximab therapy was considered. EF was 36%. With close cardiac monitoring, IFX at 5 mg/Kg for a dose of 170 mg/infusion was started. Induction therapy was completed uneventfully, and 2 months later he had gained 10 lbs, steroids were discontinued, perianal fistula had closed, and EF 46%. IFX dose was adjusted by weight. By 6 months, he had 25 lbs and EF was 56%. He has continued doing well on maintenance IFX and azathioprine. Complications of the cardiovascular system by Crohn's disease are uncommon. Most of the reported complications related to CD are myocarditis and pericarditis but dilated cardiomyopathy has been described. Vasculitis is part of the pathological spectrum of inflammatory bowel disease and the most probable mechanism for cardiovascular injury. We successfully treated a patient with CD and DCM with improvement of systolic function and clinical status. We wonder whether his DCM is an undiagnosed manifestation of CD or an unrelated complicating illness.

Microscopic colitis: pathologic considerations, changing dogma.

Microscopic colitis as an entity was first recognized in 1976, and has become one of the most frequent diseases to exclude on colonic mucosal biopsies. In some pathology practices, up to 30% of colonic biopsies received are from patients in whom microscopic colitis is the clinical question. In this review, the evolution of the terminology and early studies describing the pathology of microscopic colitis are discussed. The pathology of lymphocytic and collagenous colitis is reviewed in detail, including common diagnostic pitfalls, and what is currently known about the pathogenesis of these diseases. The differential diagnosis of microscopic colitis includes other idiopathic inflammatory bowel diseases (Crohn's and ulcerative colitis), infections, and drug reactions. The distinction between these entities and microscopic colitis is discussed in detail. Finally, recent studies have revealed new histopathologic changes in microscopic colitis that challenge the currently held concepts of how microscopic colitis fits into the spectrum of inflammatory bowel diseases.

Indeterminate colitis — broadening the perspective

A framework is proposed for a comprehensive use of the term indeterminate colitis encompassing the whole spectrum of inflammatory bowel disease with division into two surgical resection patterns and two mucosal biopsy patterns. Indeterminate colitis in resections may be of acute and non-acute type. The former is more common, being the final common pathway of fulminant colitis of several aetiologies and not just the end result of Crohn's disease and ulcerative colitis. As few patients develop small intestinal disease during follow up, restorative proctocolectomy has a favourable outcome. In biopsy practice, indeterminate colitis may also be subdivided into two groups; biopsies with normal colonoscopy represented by nonlymphocytic, non-collagenous microscopic colitis, and biopsies with abnormal colonoscopy. The latter mainly represent the overlapping pathology of active but medically controllable Crohn's disease and ulcerative colitis. In all patterns, indeterminate colitis should be viewed as a ‘pending tray’ diagnosis representing diagnostic inadequacy and not as a specific nosological entity.

Anti-neutrophil cytoplasmic antibodies (ANCA) in sera from patients with inflammatory bowel disease (IBD)

Anti-neutrophil cytoplasmic antibodies producing a perinuclear fluorescence pattern on ethanol-fixed granulocytes (p-ANCA) were found in 33 of 67 patients (49%) with ulcerative colitis (UC) but also in 14 of 35 patients (40%) with Crohn's disease (CD). In the latter condition p-ANCA were equally present in subgroups with colonic, ileocolonic, or ileal involvement only. Titers of p-ANCA were higher in patients with UC compared to CD patients, in particular when comparing patients with active disease. In contrast to findings in CD, patients with active UC had higher titers of p-ANCA than patients with inactive UC. Although p-ANCA were incidentally directed to lactoferrin, both in UC and CD, and to proteinase-3 and myeloperoxidase in UC only, the antigenic nature of p-ANCA could not be identified in most of the cases. We conclude that, within the spectrum of inflammatory bowel disease, the presence of p-ANCA is not specific for UC. When titers of p-ANCA are taken into account, the presence of high-titered p-ANCA, however, suggests active UC.

T cell antigen receptor V gene usage. Increases in V beta 8+ T cells in Crohn's disease.

Crohn's disease represents part of a spectrum of inflammatory bowel diseases characterized by immune regulatory defects and genetic predisposition. T cell antigen receptor V gene usage by T lymphocytes was investigated using four MAbs specific for various V gene products. One MAb (Ti3a), reactive with V beta 8 gene products, detected increased numbers of T cells in a subset of Crohn's disease patients as compared with normal controls and ulcerative colitis patients. In family studies there was no apparent inherited predisposition to the use of V beta 8 genes, and there was no association between a restriction fragment length polymorphism of the V beta 8.1 gene and Crohn's disease. The V beta 8+ T cells were concentrated in the mesenteric lymph nodes draining the inflammatory lesions and belonged to both the CD4+ and CD8+ T cell subsets. In contrast, lamina propria and intraepithelial T cells were not enriched in V beta 8+ T cells, suggesting that these cells were participating in the afferent limb of a gut-associated immune response. The expanded V beta 8+ T cells in Crohn's disease appear to result from an immune response to an as yet unknown antigen.

Overlap in the spectrum of non-specific inflammatory bowel disease--'colitis indeterminate'.

It is stated that 10-20% of cases of non-specific inflammatory bowel disease cannot be classified. Thirty such cases, designated colitis indeterminate at the time of colectomy, were identified from the pathology files of St. Mark's Hospital. The Histopathological features of the surgical specimens and any available biopsy specimens were studied. In nearly all the cases urgent surgery had been required and the features of incipient or established fulminating disease were present. The pathology of these cases of Crohn's disease and ulcerative colitis overlapped, and differentiating features were scant or unreliable. Accepted criteria of Crohn's disease--namely, fissuring ulceration, transmural inflammation, and a maintained goblet-cell population--were found in cases subsequently proved to be ulcerative colitis. Disease activity greatly affected the evaluation of morphological features. Many of the difficulties were resolved when biopsy material obtained during a quiescent phase was examined. The specimens gave a dynamic perspective of the disease process, often more valuable than the static, non-specific picture of acute disease seen in the surgical specimens. Case of colitis indeterminate form a small distinctive group in the spectrum of inflammatory bowel disease which is characterised by a common pattern of pathology that presents a diagnostic dilemma.