Absence Of Colitis Research Articles

Calprotectin in Bile

Our aim was to evaluate the diagnostic potential of calprotectin in serum and bile of patients with primary sclerosing cholangitis (PSC). PSC is a chronic cholestatic liver disease of unknown etiology. It is characterized by progressive inflammation and fibrosis of the bile ducts leading to biliary cirrhosis and eventually liver failure. Reliable markers for disease activity and severity are still lacking. Subunits of calprotectin, a fecal marker of inflammation in inflammatory bowel disease, have been recently identified in bile. Calprotectin was measured in patients with PSC (n=56), cholangiocarcinoma (CC) complicating PSC (CC/PSC) (n=13), CC (n=30), and bile duct stones in bile (n=38) and serum (n=73) by enzyme-linked immunosorbent assay in a cross-sectional study. PSC patients were categorized by the Mayo risk score (MRS) to characterize the disease severity. Calprotectin is present in bile, and the median concentration was significantly higher in PSC patients (P<0.05). Stratification of PSC patients by MRS showed significantly elevated calprotectin levels in bile in the MRS-high group (P<0.05). Calprotectin and MRS correlated significantly (P<0.05). The presence or absence of inflammatory bowel disease in PSC patients did not alter calprotectin levels in bile. Serum AP and calprotectin in bile correlated significantly (P=0.013). No significant correlation was found for other liver-related parameters. In contrast, serum calprotectin levels were significantly higher in patients with CC, but there was no association with PSC or disease activity/severity. Calprotectin in bile is a promising disease marker in patients with PSC with a potential prognostic value.

Primary anorectal Hodgkin lymphoma: report of a case and review of the literature

Primary colorectal lymphomas are very rare. They are mostly B-cell non-Hodgkin lymphomas. Only 2 cases of anorectal Hodgkin lymphoma have been described so far, both affecting HIV-infected males and showing Epstein-Barr virus infection. We report an unusual case of primary Hodgkin lymphoma of the anorectal region in an HIV-negative, Epstein-Barr virus-infected patient and in the absence of inflammatory bowel disease. The importance of distinguishing Hodgkin lymphoma from Epstein-Barr virus-induced lymphoproliferative disorders and from Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly is stressed in particular in non-immunocompromised patients and in the absence of history of inflammatory bowel disease.

Sex-dependent control of murine emotional-affective behaviour in health and colitis by peptide YY and neuropeptide Y.

Peptide YY (PYY) and neuropeptide Y (NPY) are involved in regulating gut and brain function. Because gastrointestinal inflammation is known to enhance anxiety, we explored whether experimental colitis interacts with genetic deletion (knockout) of PYY and NPY to alter emotional-affective behaviour. Male and female wild-type, NPY (NPY(-/-) ), PYY (PYY(-/-) ) and NPY(-/-) ; PYY(-/-) double knockout mice were studied in the absence and presence of mild colitis induced by ingestion of dextran sulphate sodium (2%) in drinking water. Anxiety-like behaviour was tested on the elevated plus maze and open field, and depression-like behaviour assessed by the forced swim test. In the absence of colitis, anxiety-like behaviour was increased by deletion of NPY but not PYY in a test- and sex-dependent manner, while depression-like behaviour was enhanced in NPY(-/-) and PYY(-/-) mice of either sex. The severity of DSS-induced colitis, assessed by colonic myeloperoxidase content, was attenuated in NPY(-/-) but not PYY(-/-) mice. Colitis modified anxiety- and depression-related behaviour in a sex-, genotype- and test-related manner, and knockout experiments indicated that NPY and PYY were involved in some of these behavioural effects of colitis. These data demonstrate sex-dependent roles of NPY and PYY in regulation of anxiety- and depression-like behaviour in the absence and presence of colitis. Like NPY, the gut hormone PYY has the potential to attenuate depression-like behaviour but does not share the ability of NPY to reduce anxiety-like behaviour.

Routine use of inflammatory markers in paediatric inflammatory bowel disease

IntroductionRoutine blood investigations are regularly performed in secondary and tertiary care to aid in predicting the presence or absence of intestinal inflammation. There is a need for laboratory costs and...

Heligmosomoides polygyrus Infection Can Inhibit Colitis through Direct Interaction with Innate Immunity

Less developed countries have a low incidence of immunological diseases like inflammatory bowel disease (IBD), perhaps prevented by the high prevalence of helminth infections in their populations. In the Rag IL-10(-/-) T cell transfer model of colitis, Heligmosomoides polygyrus, an intestinal helminth, prevents and reverses intestinal inflammation. This model of colitis was used to explore the importance of innate immunity in H. polygyrus protection from IBD. Rag mice briefly exposed to H. polygyrus before reconstitution with IL-10(-/-) colitogenic T cells are protected from colitis. Exposure to H. polygyrus before introduction of IL-10(-/-) and OT2 T cells reduced the capacity of the intestinal mucosa to make IFN-gamma and IL-17 after either anti-CD3 mAb or OVA stimulation. This depressed cytokine response was evident even in the absence of colitis, suggesting that the downmodulation in proinflammatory cytokine secretion was not just secondary to improvement in intestinal inflammation. Following H. polygyrus infection, dendritic cells (DCs) from the lamina propria of Rag mice displayed decreased expression of CD80 and CD86, and heightened expression of plasmacytoid dendritic cell Ag-1 and CD40. They were also less responsive to lamina proprias, producing less IL-12p40 and IL-10. Also diminished was their capacity to present OVA to OT2 T cells. These experiments infer that H. polygyrus does not require direct interactions with T or B cells to render animals resistant to colitis. DCs have an important role in driving both murine and human IBD. Data suggest that phenotypic alternations in mucosal DC function are part of the regulatory process.

Vitamin D deficiency in mice impairs colonic antibacterial activity and predisposes to colitis.

Vitamin D insufficiency is a global health issue. Although classically associated with rickets, low vitamin D levels have also been linked to aberrant immune function and associated health problems such as inflammatory bowel disease (IBD). To test the hypothesis that impaired vitamin D status predisposes to IBD, 8-wk-old C57BL/6 mice were raised from weaning on vitamin D-deficient or vitamin D-sufficient diets and then treated with dextran sodium sulphate (DSS) to induce colitis. Vitamin D-deficient mice showed decreased serum levels of precursor 25-hydroxyvitamin D(3) (2.5 +/- 0.1 vs. 24.4 +/- 1.8 ng/ml) and active 1,25-dihydroxyvitamin D(3) (28.8 +/- 3.1 vs. 45.6 +/- 4.2 pg/ml), greater DSS-induced weight loss (9 vs. 5%), increased colitis (4.71 +/- 0.85 vs. 1.57 +/- 0.18), and splenomegaly relative to mice on vitamin D-sufficient chow. DNA array analysis of colon tissue (n = 4 mice) identified 27 genes consistently (P < 0.05) up-regulated or down-regulated more than 2-fold in vitamin D-deficient vs. vitamin D-sufficient mice, in the absence of DSS-induced colitis. This included angiogenin-4, an antimicrobial protein involved in host containment of enteric bacteria. Immunohistochemistry confirmed that colonic angiogenin-4 protein was significantly decreased in vitamin D-deficient mice even in the absence of colitis. Moreover, the same animals showed elevated levels (50-fold) of bacteria in colonic tissue. These data show for the first time that simple vitamin D deficiency predisposes mice to colitis via dysregulated colonic antimicrobial activity and impaired homeostasis of enteric bacteria. This may be a pivotal mechanism linking vitamin D status with IBD in humans.

An unusual Spigelian hernia involving the appendix: a case report

IntroductionSpigelian herniae are uncommon and frequently pose a diagnostic challenge.Case presentationWe report the case of a 71-year-old man in whom an ischaemic appendix was found within the sac of a Spigelian hernia during emergency repair.ConclusionsThere are very few reported cases in which an appendix has been found within a Spigelian hernia, in the absence of inflammatory bowel disease. An awareness of the range of viscera which may be encountered in Spigelian herniae is important for safe repair.

Gastrointestinal Norovirus Infection Associated With Exacerbation of Inflammatory Bowel Disease

In this study we aimed to determine, in pediatric patients, whether norovirus infection could be associated with exacerbations of inflammatory bowel disease (IBD) and ascertain whether the clinical expression of norovirus gastroenteritis was similar in patients with IBD compared with non-IBD controls. We performed a case-control retrospective chart review, over a 10-month interval, of patients with IBD with an exacerbation of their disease. The presence of norovirus in stool and/or rectal swab samples, as determined by an enzyme-linked immunoassay, was assessed. In addition, sex, age, type of IBD, presence or absence of diarrhea, hematochezia, and the need for hospitalization were determined. A similar number of control patients who did not have IBD were used as controls. Nine patients with IBD (8 ulcerative colitis/1 Crohn disease) had exacerbations with diarrhea. Eight had norovirus antigen in at least 1 sample. All 9 patients with IBD presented with bloody diarrhea and 6 of the 8 norovirus-positive patients with IBD required hospitalization. All of the control patients experienced diarrhea; however, no hematochezia was noted and no hospitalization was required. Several patients with IBD and controls remained positive for norovirus months after the initial positive stool and/or rectal swab sample. The virus appeared to be more common during winter months. We conclude that norovirus may be associated with exacerbations of IBD. When norovirus accompanies IBD it is more likely to be associated with hematochezia than when the infection occurs in the absence of IBD.

This Month in Gastroenterology

This Month in Gastroenterology

Regulatory CD4+CD25+ T Cells Prevent Thymic Dysfunction in Experimental Chronic Colitis

Chronic colitis in T-cell deficient Tg epsilon26 mice develops due to a dysfunction of the thymus which generates colitogenic T cells after bone marrow (BM) transplantation. Regulatory CD4+ CD25+ T cells have been shown to prevent colitis in this model by normalizing the peripheral T-cell pool. We tested the hypothesis that T-cell normalization takes place in the thymus. Tg epsilon26 mice were transplanted with BM (BM-->Tg epsilon26 mice) and consequently received either CD4+ CD25+ or CD4+ CD25- cells from syngenic wild type mice. Furthermore, untransplanted Tg epsilon26 mice received CD4+ CD25+ or CD4+ CD25- cells or complete mesenteric lymph node cells. Transfer of regulatory. CD4+ CD25+ cells normalized the total number of thymocytes and the percentage and number of double positive CD4+ CD8+ cells in transplanted mice while percentage of single positive CD4+ and CD8+ thymocytes in BM-->Tg epsilon26 mice was reduced upon CD4+ CD25+ transfer. Timing of CD4+ CD25+ cell injection was important as transfer later than 7 days after BM transplantation failed to prevent abnormal thymic T-cell distribution in BM-->Tg epsilon26 mice. Isolated CD4+ CD25+ cell transfer without preceding BM transplantation failed to reconstitute thymic architecture. Differences of thymic cell composition could not be exclusively explained by presence or absence of colitis, respectively, because 19 days after BM transplantation when both groups showed no histological signs of colitis, animals transferred with CD4+ CD25+ T cells had a significantly higher percentage and number of CD4+ CD25+ thymocytes and CD4+ Foxp3+ cells than BM-->Tg epsilon26 mice. In conclusion, early CD4+ CD25+ cotransfer prevents thymic dysfunction which underlies immune-mediated bowel inflammation in BM-->Tg epsilon26 mice.

DOES HAVING A FAMILY HISTORY OF INFLAMMATORY BOWEL DISEASE AFFECT QUALITY OF LIFE IN NEWLY DIAGNOSED CHILDREN?

Background: Data on health related quality of life (HRQOL) in children with inflammatory bowel disease (IBD) are limited. We sought to evaluate changes in HRQOL in a cohort of newly diagnosed children with IBD and to determine whether a family history (FH) of IBD influences outcome. Methods: Data from a prospective, multi-center observational registry recording clinical and laboratory outcomes in newly diagnosed children between the ages of 9 and 16 yrs were examined to identify study subjects. Subjects who had completed IMPACT-35, a previously validated HRQOL instrument at diagnosis and one year, were eligible for study. Notation was made of the presence or absence of IBD in a parent or sibling of the study subject. Results: 206 subjects met inclusion criteria (mean age 12.7 yr, 46% female, 73% Crohn disease, 23% ulcerative colitis, 4% indeterminate colitis). 29 subjects (14%) had a parent/sibling with IBD. The distribution of UC/CD/IC, disease severity at diagnosis, need for surgery, hospitalization, or types of medications during the first year was similar in both groups. Mean IMPACT scores at diagnosis were 123 (+) FH and 124 (−) FH (out of maximum of 170) and improved in both groups to 137 and 142, respectively. Improvements were noted in both groups for bowel symptoms, systemic symptoms, emotional functioning, social functioning, and body image. A trend was noted for children with a (+) FH being less bothered by taking medication than children with a (−) FH. Conclusions: HRQOL improves in children with IBD in the year following diagnosis and is not affected by having a parent/sibling with IBD. Taking medications is a significant issue for all children with newly diagnosed IBD, but a (+) FH appears to lessen the problem. As adherence to medication regimens is important, our data suggest the need for additional interventions in this area.

Colitogenic and non‐colitogenic commensal bacteria differentially trigger DC maturation and Th cell polarization: An important role for IL‐6

We investigated whether commensal bacteria modulate activation and maturation of bone marrow-derived DC and their ability to prime CD4(+) T cells. We used Escherichia coli mpk, which induces colitis in gnotobiotic IL-2-deficient (IL-2(-/-)) mice, and Bacteroides vulgatus mpk, which prevents E. coli-induced colitis. Stimulation of DC with E. coli induced TNF-alpha, IL-12 and IL-6 secretion and expression of activation markers. Moreover, stimulation of DC with E. coli increased T cell activation and led to Th1 polarization. Stimulation with B. vulgatus led only to secretion of IL-6, and DC were driven into a semi-mature state with low expression of activation markers and did not promote Th1 responses. B. vulgatus-induced semi-mature DC were non-responsive to stimulation by E. coli in terms of maturation, T cell priming and TNF-alpha but not IL-6 production. The non-responsiveness of B. vulgatus-stimulated DC was abrogated by addition of anti-IL-6 mAb or mimicked with rIL-6. These data suggest that B. vulgatus-induced IL-6 drives DC into a semi-mature state in which they are non-responsive to proinflammatory activation by E. coli. This in vitro mechanism might contribute to the prevention of E. coli-triggered colitis development by B. vulgatus in vivo; high IL-6 mRNA expression was consistently found in B. vulgatus-colonized or B. vulgatus/E. coli co-colonized IL-2(-/-) mice and was associated with absence of colitis.

Additional human β2‐microglobulin curbs HLA–B27 misfolding and promotes arthritis and spondylitis without colitis in male HLA–B27–transgenic rats

Ankylosing spondylitis and related spondylarthritides are associated with HLA-B27, and also with intestinal inflammation, by unknown mechanisms. The folded HLA-B27 molecule is a trimer of heavy chain, beta2-microglobulin (beta2m), and short peptide. However, B27 heavy chain has an unusual propensity to misfold and trigger the unfolded protein response (UPR). This study was initiated to test the hypothesis that B27 misfolding plays a role in the pathogenesis of spondylarthritis. Rats with high transgene copy numbers of HLA-B27 heavy chain together with human beta2m (Hubeta2m) spontaneously develop colitis, peripheral arthritis, and occasional spondylitis, and those with lower transgene copy numbers remain healthy. We crossed disease-prone and healthy HLA-B27/Hubeta2m-transgenic rat lines with a healthy line, 283-2, carrying only the Hubeta2m transgene. HLA-B27 assembly was assessed by pulse-chase analysis of B27 molecules, and UPR triggering was assessed by measuring BiP/Grp78 messenger RNA (mRNA) in splenic concanavalin A blasts. Surface expression of B27 and Hubeta2m was determined by flow cytometry. Disease manifestations were identified by clinical observation, histology, and measurement of cytokine mRNA. The extra Hubeta2m from the 283-2 line significantly reduced B27 misfolding and UPR triggering. Unexpectedly, however, F1 male offspring of the healthy 21-3 line crossed with the 283-2 line showed a high prevalence, severity, and duration of arthritis and spondylitis, in the absence of colitis. The arthropathy showed many features characteristic of human spondylarthritis. These results suggest that B27 misfolding is associated with intestinal inflammation, but that neither B27 misfolding nor intestinal inflammation is critical to the development of B27-associated arthropathy.

Sclerosing cholangitis

Primary sclerosing cholangitis in children can mimic autoimmune hepatitis in the absence of inflammatory bowel disease. Most adult patients have been identified with human leukocyte antigens that either predispose or protect against disease. Novel class I alleles and cytokine polymorphisms may also contribute to disease susceptibility. Primary alpha-hemolytic streptococci infection does not appear to directly cause primary sclerosing cholangitis. Promising diagnostic modalities such as single photon emission tomography require further study in comparison with cholangiographic techniques. Positron-emission tomography and DNA cytometry appear promising for confirming occult cholangiocarcinoma when present. The chemoprevention effects of ursodeoxycholic acid on colorectal dysplasia await further investigation. Initial results from high-dose ursodeoxycholic acid in halting disease progression, however, suggest a beneficial effect. In contrast, the impact of endoscopic therapy on natural history remains unresolved. Although liver transplantation continues to be effective for end-stage liver disease, disease recurrence in the allograft is a controversial topic.

Autoimmune liver disease

Autoimmune hepatitis in children may be associated with sclerosing cholangitis in the absence of inflammatory bowel disease. Wilson disease can have clinical and laboratory features that resemble autoimmune hepatitis, and it may respond initially to corticosteroids. Soluble HLA-DR antigens reflect clinical activity, and they may be useful markers of treatment response. Polymorphisms of the cytotoxic T lymphocyte antigen-4 gene may synergize with other autoimmune promoters or HLA risk factors to increase susceptibility and alter disease expression. DRB1*1301 distinguishes Argentine children from Argentine adults and identifies a unique subgroup. Antibodies to soluble liver antigen/liver-pancreas do not characterize a separate clinical entity. Their target antigen has been isolated, and it shares homologies with a selenocysteine-specific protecting factor (tRNP((Ser)Sec)). CYP2D6 is expressed on the hepatocyte surface, and it can be targeted by antibodies in autoimmune hepatitis and chronic hepatitis C. Perinuclear antineutrophil cytoplasmic antibodies lack sensitivity and specificity for autoimmune hepatitis, and they have diverse antigen specificities. Activation-induced cell death may be impaired in autoimmune hepatitis, and, in contrast to budesonide, mycophenolate mofetil has been effective in a small study of problematic patients.

Clinical features and treatment of peristomal pyoderma gangrenosum.

Peristomal pyoderma gangrenosum (PPG), an unusual variant of pyoderma gangrenosum, has been reported almost exclusively in patients with inflammatory bowel disease (IBD) and is frequently misdiagnosed. To better characterize the clinical manifestations, diagnosis, and management of PPG. Retrospective analysis of 7 patients with PPG observed in a university-affiliated community setting between 1988 and December 1999. Clinical and histopathologic features, associated disorders, and microbiologic findings. Two patients had Crohn disease, 2 had ulcerative colitis, and 3 had abdominal cancer. Five patients had at least 1 relapse of PPG after initial healing. Although 3 of 4 patients with IBD had active bowel disease, a parallel course with PPG occurred in only 1 patient. Both patients whose stoma was relocated developed an ulcer at the new site. Effective therapies included topical superpotent corticosteroids; intralesional injection of triamcinolone acetonide at the ulcer margin; topical cromolyn sodium; oral dapsone, prednisone, cyclosporine, mycophenolate mofetil; and intravenous infliximab. Our experiences demonstrate that although PPG has been most often reported in patients with IBD, it may occur in the absence of IBD. Biopsy of the skin lesion is not diagnostic but excludes other causes. Relocation of the stoma may be associated with a new ulceration and should be avoided. Trauma to the skin of a predisposed patient may elicit the pustules or ulcerations associated with pathergy. JAMA. 2000;284:1546-1548.

Autoimmune cholangitis within the spectrum of autoimmune liver disease.

Autoimmune cholangitis is an idiopathic disorder with mixed hepatocellular and cholestatic findings. Our goal was to characterize the disease prospectively by application of uniform diagnostic criteria. Twenty patients were identified and compared with 242 patients with conventional forms of autoimmune liver disease. Patients with autoimmune cholangitis were distinguished from type 1 autoimmune hepatitis (AIH) by lower serum levels of aspartate transaminase (AST), gamma-globulin, and immunoglobulin G; higher serum levels of alkaline phosphatase; and lower frequencies of autoantibodies. They were distinguished from primary biliary cirrhosis (PBC) by higher serum levels of AST and bilirubin, lower serum concentrations of immunoglobulin M, and greater occurrence of autoantibodies. Their female predominance, lower serum alkaline phosphatase levels, higher frequency of autoantibodies, and absence of inflammatory bowel disease differentiated them from primary sclerosing cholangitis (PSC). Laboratory findings ranged widely and did not characterize individual patients. HLA risk factors were similar to those of type 1 AIH and PBC, and different from those of PSC. Treatment responses to corticosteroids or ursodeoxycholic acid were poor. Composite histological patterns resembled mainly PBC or PSC. We conclude that autoimmune cholangitis diagnosed by prospective analysis cannot be assimilated into a single, conventional, diagnostic category. It may represent variant forms of diverse conditions, a transition stage, or a separate entity with varying manifestations.

P53 and β Catenin Expression in Chronic Ulcerative Colitis–Associated Polypoid Dysplasia and Sporadic Adenomas

In patients with chronic ulcerative colitis (CUC), polypoid dysplastic lesions (PDLs) are morphologically similar to sporadic adenomas (SAs), but may be biologically distinct from them and are managed differently. p53 mutations have been shown to occur at an earlier phase in the progression of CUC-associated neoplasia when compared with sporadic colon carcinogenesis. In contrast, APC gene mutations are common and occur at an earlier stage in the development of SA. beta catenin is a cell membrane protein that accumulates in the nucleus of colon cancer cells in response to APC gene mutations. This study was performed to test the hypothesis that CUC-associated PDLs have a different molecular profile than do CUC-associated SAs and therefore may be distinguished on this basis. Mucosal biopsy specimens of 38 benign polypoid epithelial neoplasms (17 CUC-associated PDLs and 21 CUC-associated SAs) from 33 patients with CUC and 13 SAs from patients without CUC (controls) were immunohistochemically stained for p53 and beta catenin and graded as follows: 0 = no staining, 1+ = <50% of cells positive, and 2+ = > or =50% of cells positive. The results were correlated with the clinical and histologic features and compared between the two CUC-associated polyp subgroups. Overall, six (16%) polyps were p53-positive, of which five were CUC-associated PDLs (one 1+ and four 2+) and one was a CUC-associated SA (1+) (p = 0.05). Strong (2+) p53 positivity was detected, however, in only CUC-associated PDLs (4 of 5; 80%). Nine of 32 polyps evaluated for beta catenin were positive and included 1 (8%) of 12 CUC-associated PDLs and 8 (40%) of 20 CUC-associated SAs (p = 0.06). Two of the nine beta catenin polyps were strongly positive, and both were CUC-associated SAs. Non-CUC-associated (control) SAs were positive for p53 and beta catenin in 2 (15%) of 13 and 6 (46%) of 13 cases, but none in a strong (2+) fashion. No differences were observed in p53 or beta catenin staining, between CUC-associated and non-CUC-associated SAs. Neither p53 nor beta catenin expression correlated with any clinical or pathologic features, including size and degree of dysplasia of the polyps. CUC-associated PDLs and CUC-associated SAs may have a different molecular genotype. In patients with CUC, the combination of strong p53 expression and absent or weak beta catenin expression is evidence in favor of a CUC-associated PDL in diagnostically difficult lesions. Furthermore, CUC-associated and non-CUC-associated SAs have a similar P53 and beta catenin immunophenotype and thus provide evidence that they are pathogenetically related neoplasms regardless of the presence or absence of colitis.

Enteric microflora in IBD: Pathogens or commensals?

: Both pathogenic and normal enteric microflora can induce and perpetuate chronic intestinal inflammation with systemic manifestations in genetically susceptible hosts. At the present time, there is no convincing indication that the majority of cases of ulcerative colitis or Crohn's disease is caused by persistent infection by Mycobacterium paratuberculosis, measles, Listeria monocytogenes, or Helicobacter species, but this possibility remains a valid hypothesis. Transient infection with any of a number of pathogens including upper respiratory tract infections and common enteric pathogens could provide one of the environmental triggers that initiate or reactivate IBD, which is then perpetuated in susceptible hosts by resident (not pathogenic) commensal luminal bacteria. Recent results in animal models demonstrate the absence of colitis, gastritis, and arthritis in a sterile (germ-free) environment, showing the importance of resident bacteria as persistent antigenic stimuli in the genetically susceptible hosts. Furthermore, there is an indication that not all normal luminal bacteria have equal capacities to induce mucosal injury, since some species can induce inflammation (Bacteroides), some are neutral (E. coli) and others may be protective (Lactobacilli). These observations have important therapeutic implications, such that altering luminal bacterial components and thereby decreasing the persistent antigenic drive offer alternative or adjuvant approaches to ongoing efforts to block mucosal immune responses to these stimuli.

Primary sclerosing cholangitis is associated with nonsmoking: A case- control study

BACKGROUND & AIMS: Cigarette smoking is thought to protect against the development of ulcerative colitis. The relationship between a related disease, primary sclerosing cholangitis, and smoking is unknown. The aim of this study was to determine if the relationship between smoking and sclerosing cholangitis is similar to that found between smoking and ulcerative colitis. METHODS: A stratified sample of 184 patients with primary sclerosing cholangitis and age- and sex-matched institutional control subjects were identified. Smoking information was obtained from a medical questionnaire completed at the time of visit. RESULTS: Eighty- one percent of the patients had associated inflammatory bowel disease. Only 4.9% of them were current smokers compared with 26.1% of the controls; 69.6% of the patients had never smoked vs. 46.7% of the controls. The estimated odds of having primary sclerosing cholangitis in current smokers compared with never-smokers was 0.13. The odds of having disease among former and current users of any tobacco relative to never-users was 0.41 regardless of the presence or absence of inflammatory bowel disease. CONCLUSIONS: The odds of having primary sclerosing cholangitis was significantly decreased among current smokers. Concomitant ulcerative colitis does not fully explain the association between nonsmoking and primary sclerosing cholangitis. Smoking may exert its protective effect in a systemic, rather than colonic, manner. (Gastroenterology 1996 May;110(5):1496-502)