An outbreak of Yersinia enterocolitica in a captive colony of African green monkeys (Chlorocebus aethiops sabaeus) in the Caribbean

USDA-ARS?s Scientific Manuscript database

Yersinia enterocolitica is a zoonotic gram-negative pathogen that causes mesenteric lymphadenitis, terminal ileitis, acute gastroenteritis, and septicemia in domestic animals and primates. In 2012, 46 captive African green monkeys (Chlorocebus aethiops sabaeus) died during an outbreak of acutely fat...

The long-term outcome of restorative operation in Crohn's disease: influence of location, prognostic factors and surgical guidelines.

PubMed Central

Trnka, Y M; Glotzer, D J; Kasdon, E J; Goldman, H; Steer, M L; Goldman, L D

1982-01-01

The course of all 113 patients with Crohn's disease whose initial procedure involved an anastomosis operated upon from 1942 to 1972 was followed through 1980. The calculated cumulative 30-year total mortality was 23.4%, 16.7% disease-related. The cumulative recurrence rate was 29% at five years, 52% at ten years, 64% at 15 years and 84% at 25 years, with no important differences between disease locations and types of operation. Sex, age, duration, granulomas, enteral or perirectal fistulas and length of the resection, the disease, and the proximal resection margin had no significant influence on the rates of development of recurrent disease or on functional outcome. By far the most common site of recurrence was the neo-terminal ileum, but in ileocolitis compared with ileitis, recurrence was 5.2 times more likely (p = 0.0001) to involve the adjacent or remote colon as well. Moreover, only 1/63 ileitis patients eventually required ileostomy, whereas 15/47 patients with ileocolitis or colitis ultimately required this procedure (p less than 0.001). The current status of the patients was excellent or good in 64% and unwell or dead related in 24%. Urolithiasis developed in 19%. PMID:7114939

MRI diffusion-weighted imaging (DWI) in pediatric small bowel Crohn disease: correlation with MRI findings of active bowel wall inflammation.

PubMed

Ream, Justin M; Dillman, Jonathan R; Adler, Jeremy; Khalatbari, Shokoufeh; McHugh, Jonathan B; Strouse, Peter J; Dhanani, Muhammad; Shpeen, Benjamin; Al-Hawary, Mahmoud M

2013-09-01

Restricted diffusion on diffusion-weighted imaging (DWI) sequences during magnetic resonance enterography (MRE) has been shown in segments of bowel affected by Crohn disease. However, the exact meaning of this finding, particularly within the pediatric Crohn disease population, is poorly understood. The purpose of this study was to determine the significance of bowel wall restricted diffusion in children with small bowel Crohn disease by correlating apparent diffusion coefficient (ADC) values with other MRI markers of disease activity. A retrospective review of pediatric patients (≤ 18 years of age) with Crohn disease terminal ileitis who underwent MRE with DWI at our institution between May 1, 2009 and May 31, 2011 was undertaken. All of the children had either biopsy-proven Crohn disease terminal ileitis or clinically diagnosed Crohn disease, including terminal ileal involvement by imaging. The mean minimum ADC value within the wall of the terminal ileum was determined for each examination. ADC values were tested for correlation/association with other MRI findings to determine whether a relationship exists between bowel wall restricted diffusion and disease activity. Forty-six MRE examinations with DWI in children with terminal ileitis were identified (23 girls and 23 boys; mean age, 14.3 years). There was significant negative correlation or association between bowel wall minimum ADC value and established MRI markers of disease activity, including degree of bowel wall thickening (R = (-)0.43; P = 0.003), striated pattern of arterial enhancement (P = 0.01), degree of arterial enhancement (P = 0.01), degree of delayed enhancement (P = 0.045), amount of mesenteric inflammatory changes (P < 0.0001) and presence of a stricture (P = 0.02). ADC values were not significantly associated with bowel wall T2-weighted signal intensity, length of disease involvement or mesenteric fibrofatty proliferation. Increasing bowel wall restricted diffusion (lower ADC values) is associated with multiple MRI findings that are traditionally associated with active inflammation in pediatric small bowel Crohn disease.

From intestinal stem cells to inflammatory bowel diseases

PubMed Central

Gersemann, Michael; Stange, Eduard Friedrich; Wehkamp, Jan

2011-01-01

The pathogenesis of both entities of inflammatory bowel disease (IBD), namely Crohn’s disease (CD) and ulcerative colitis (UC), is still complex and under investigation. The importance of the microbial flora in developing IBD is beyond debate. In the last few years, the focus has changed from adaptive towards innate immunity. Crohn’s ileitis is associated with a deficiency of the antimicrobial shield, as shown by a reduced expression and secretion of the Paneth cell defensin HD5 and HD6, which is related to a Paneth cell differentiation defect mediated by a diminished expression of the Wnt transcription factor TCF4. In UC, the protective mucus layer, acting as a physical and chemical barrier between the gut epithelium and the luminal microbes, is thinner and in part denuded as compared to controls. This could be caused by a missing induction of the goblet cell differentiation factors Hath1 and KLF4 leading to immature goblet cells. This defective Paneth and goblet cell differentiation in Crohn’s ileitis and UC may enable the luminal microbes to invade the mucosa and trigger the inflammation. The exact molecular mechanisms behind ileal CD and also UC must be further clarified, but these observations could give rise to new therapeutic strategies based on a stimulation of the protective innate immune system. PMID:21912468

Persistent Campylobacter Jejuni Infections in Patients Infected with Human Immunodeficiency Virus (HIV)

DTIC Science & Technology

1988-04-01

on the fifth hospital day h-is found in the Leum. Gram and Warthin -Starry stains showed stone-filled gallbladder was removed; the intraoperative exami...colonoscopic findings were considered to be all antibiotic treatments tested. Erythromycin therapy was con- most consistent with Crohn ileitis, prednisone...erally, he had 6 to 10 watery stools per day for 3 weeks each manIA). month. Sigmoidoscopic findings were consistent with Crohn ifornia). disease

Recurrent Crohn's disease in the duodenum and jejunum following extensive small bowel resection and jejunocolonic anastamosis: radiologic findings in twenty-five patients.

PubMed

Zalev, A H; Prokipchuk, E J; Jeejeebhoy, K N; Gardiner, G W; Pron, G

1999-01-01

To evaluate the radiologic features of recurrent Crohn's disease after extensive enteric resection and jejunocolostomy. We reviewed the small bowel studies of 25 patients with recurrent enteritis and less than 125 cm of jejunum following enteric resection and jejunocolostomy and the studies of 27 patients with jejunitis in an intact jejunum. Twenty-three patients with recurrences had neoterminal jejunitis, six under 10 cm, 10 over 10 cm and continuous, and seven with skip lesions (six jejunal, one duodenal). Two had isolated jejunitis or duodenitis. Three with continuous disease had lengthy recurrences. Enteritis showed only one or two abnormalities in 12 of 25 patients with recurrences and in two of 27 with disease in the intact jejunum. Recurrent jejunitis and jejunitis in the intact jejunum showed similar frequencies of mucosal thickening, strictures, ulceration and its complications, skip lesions, sacculation, obstructive dilatation, featureless mucosa, and polyps, and significantly different frequencies only of mesenteric masses. Recurrent jejunitis and terminal ileitis showed significantly different frequencies of mucosal thickening, strictures, ulceration and its complications, skip lesions, sacculation, obstructive dilatation, and mesenteric masses, and similar frequencies only of a featureless mucosa. The neoterminal jejunum is the most common site of recurrence and the only site in almost 25%. Jejunitis remote from the fecal stream is also frequent, but duodenitis is not. Recurrences are seldom extensive and often show only one or two radiographic findings. The frequencies of most lesions in recurrent jejunitis do not differ significantly from those in jejunitis in the intact jejunum but do differ from those in terminal ileitis.

Expression and regulation of the chemokine CXCL16 in Crohn’s disease and models of intestinal inflammation

PubMed Central

Diegelmann, Julia; Seiderer, Julia; Niess, Jan-Hendrik; Haller, Dirk; Göke, Burkhard; Reinecker, Hans-Christian; Brand, Stephan

2010-01-01

Background/Aims CXCL16 mediates adhesion and phagocytosis of both Gram-negative and Gram-positive bacteria and is a strong chemoattractant for CXCR6+ T cells. In this study, we determined the so far unknown expression and signal transduction of the novel CXCL16-CXCR6 chemokine-ligand receptor system in intestinal inflammation in vivo and in vitro. Methods CXCL16 mRNA was measured by quantitative PCR in human colonic biopsies of patients with Crohn’s disease (CD) as well as in the TNFΔARE mouse model of ileitis and in murine cytomegalovirus (MCMV)-induced colitis. CXCL16 serum levels were analyzed by ELISA. CXCL16-induced signal transduction was analyzed in IEC with phospho-specific antibodies for MAP kinases and Akt. Results We found an inverse expression pattern of CXCL16 and CXCR6 with highest CXCL16 mRNA levels in the proximal murine small intestine and highest CXCR6 mRNA expression in the distal colon. CXCL16 and CXCR6 mRNA were expressed in colorectal cancer (CRC)-derived IEC lines. CRC-expressed CXCR6 was functional as demonstrated by CXCL16-induced MAP kinase and Akt activation. Intestinal CXCL16 expression was elevated in the TNFΔARE mouse model of ileitis and in MCMV-induced colitis (p<0.05) and in the sera and colons of patients with CD (p<0.05), where its expression correlated highly with CXCR6 and IL-8 levels (r=0.85 and 0.89, respectively). Conclusion CRC-derived IEC express the functional CXCL16 receptor CXCR6. CXCL16 mRNA and protein expression is up-regulated in intestinal inflammation in vitro and in CD patients, suggesting an important role for this chemokine in intestinal inflammation. PMID:20848509

Reactive gastropathy is associated with inflammatory conditions throughout the gastrointestinal tract.

PubMed

Maguilnik, I; Neumann, W L; Sonnenberg, A; Genta, R M

2012-10-01

The epidemiology of reactive gastropathy and its relationship with other conditions of the gastrointestinal tract associated with NSAID use have not been evaluated. To test the hypothesis that if reactive gastropathy shares common aetiological factors with these conditions, the analysis of a large cohort would unveil associations. We queried a national pathology database for subjects with a diagnosis of reactive gastropathy; controls were patients with normal gastric biopsies. We also extracted diagnoses of H. pylori infection, intestinal metaplasia, duodenal lymphocytosis, duodenitis, ileitis, microscopic colitis and focal colitis. Of 504 011 patients with gastric biopsies, 69 101 had oesophageal, 166 134 duodenal, 13 010 ileal and 83 334 colonic biopsies. Reactive gastropathy was diagnosed in 15.6% of patients, H. pylori infection in 10.3% and normal gastric mucosa in 16.3%. Reactive gastropathy was evenly distributed across the US and increased from 2.0% in the first decade of life to >20% in octogenarians. Compared with controls, reactive gastropathy was significantly associated with Barrett's mucosa (OR 1.21 95% CI 1.16-129); duodenitis (OR 1.36; 95% CI 1.28-1.44); duodenal intraepithelial lymphocytosis (OR 1.25; 95% CI 1.13-1.39); active ileitis (OR 1.88; 95% CI 1.47-2.40); focal active colitis (OR 1.57; 95% CI 1.33-1.86); and collagenous colitis (OR 1.50; 95% CI 1.12-2.03). Reactive gastropathy, a common histopathological feature of the stomach, shows an age-dependent rise and is associated with changes of the digestive tract believed to be caused by NSAID use or duodenogastric reflux. However, a large fraction of reactive gastropathy remains unexplained; its frequent occurrence merits further efforts at elucidating its aetiology. © 2012 Blackwell Publishing Ltd.

Spontaneous, Immune-Mediated Gastric Inflammation in SAMP1/YitFc Mice, a Model of Crohn’s-Like Gastritis

PubMed Central

Reuter, Brian K.; Pastorelli, Luca; Brogi, Marco; Garg, Rekha R.; McBride, James A.; Rowlett, Robert M.; Arrieta, Marie C.; Wang, Xiao-Ming; Keller, Erik J.; Feldman, Sanford H.; Mize, James R.; Cominelli, Fabio; Meddings, Jonathan B.; Pizarro, Theresa T.

2011-01-01

Background & Aims Crohn’s disease (CD) can develop in any region of the gastrointestinal tract, including the stomach. The etiology and pathogenesis of Crohn’s gastritis are poorly understood, treatment approaches are limited, and there are not many suitable animal models for study. We characterized the features and mechanisms of chronic gastritis in SAMP1/YitFc (SAMP) mice, a spontaneous model of CD-like ileitis, along with possible therapeutic approaches. Methods Stomachs from specific pathogen-free and germ-free SAMP and AKR mice (controls) were evaluated histologically; the presence of Helicobacter spp. was tested in fecal pellets by PCR analysis. In vivo gastric permeability was quantified by fractional excretion of sucrose and epithelial tight junction protein expression was measured by quantitative reverse transcription PCR analysis. The effects of a proton pump inhibitor (PPI) or corticosteroids were measured and the ability of pathogenic immune cells to mediate gastritis was assessed in adoptive transfer experiments. Results SAMP mice developed Helicobacter-negative gastritis, characterized by aggregates of mononuclear cells, diffuse accumulation of neutrophils, and disruption of epithelial architecture; SAMP mice also had increased in gastric permeability compared with controls, without alterations in expression of tight junction proteins. The gastritis and associated permeability defect observed in SAMP mice were independent of bacterial colonization and reduced by administration of corticosteroids but not a PPI. CD4+ T cells isolated from draining mesenteric lymph nodes of SAMP mice were sufficient to induce gastritis in recipient SCID mice. Conclusions In SAMP mice, gastritis develops spontaneously and has many features of CD-like ileitis. These mice are a useful model to study Helicobacter-negative, immune-mediated Crohn’s gastritis. PMID:21704001

Can ultrasound be used as the primary imaging in children with suspected Crohn disease?

PubMed

Tsai, Timothy L; Marine, Megan B; Wanner, Matthew R; Cooper, Matthew L; Steiner, Steven J; Ouyang, Fangqian; Gregory Jennings, S; Karmazyn, Boaz

2017-07-01

There is growing literature on the use of ultrasound (US) for evaluation of Crohn disease in adults, but few studies have been conducted on children. Several studies demonstrated high accuracy of US in the diagnosis of Crohn disease. Using US as the primary screening imaging modality for Crohn disease can reduce health care costs, the need for sedation and ionizing radiation exposure. The aim of our study is to determine if US can be used for screening evaluation of pediatric Crohn disease. A prospective cohort study of pediatric patients undergoing MR enterography (MRE) for suspected or known history of Crohn disease was performed, with gray-scale and Doppler US of the terminal ileum done immediately before or after MRE. US images were interpreted by two radiologists (Reader 1 and Reader 2) not involved in image acquisition, in blinded and randomized fashion. US findings of Crohn disease including bowel wall thickening, wall stratification, increased vascularity on Doppler, lymphadenopathy, fat infiltration and extraintestinal complications were evaluated. MRE findings of terminal ileitis were considered the reference standard. Demographic data, body mass index (BMI), symptoms, and laboratory, endoscopic and histopathological data were obtained from electronic medical records. Forty-one patients (mean age: 13.7 years: 4.6-18.9 years) were evaluated. Mean BMI was 21.2 (range: 13-40.2); 10 patients (24.3%) were either overweight or obese. Final diagnoses were Crohn disease (n=24), ulcerative colitis (n=4) and normal/non-inflammatory bowel disease-related diagnoses (n=13). US demonstrated sensitivity of 67% and 78% and specificity of 78% and 83%, by Reader 1 and Reader 2, respectively. MRE sensitivity and specificity were 75% and 100%, respectively, compared to final clinicopathological diagnosis. Interobserver agreement between Reader 1 and Reader 2 was good (0.6< kappa <0.8). In screening for Crohn disease in children, US has limited sensitivity for detecting terminal ileitis.

Anisakiasis.

PubMed Central

Sakanari, J A; McKerrow, J H

1989-01-01

Anisakiasis is a zoonotic disease caused by the ingestion of larval nematodes in raw seafood dishes such as sushi, sashimi, ceviche, and pickled herring. Symptoms of anisakiasis include abdominal pain, nausea, vomiting, and diarrhea. Because symptoms are vague, this disease is often misdiagnosed as appendicitis, acute abdomen, stomach ulcers, or ileitis. Endoscopic examination with biopsy forceps has facilitated the diagnosis of gastric anisakiasis. Worms can be removed and identified, and a definitive diagnosis can be made. Patients generally recover with no further evidence of disease. Worms can become invasive, however, and migrate beyond the stomach, penetrating the intestine, omentum, liver, pancreas, and probably the lungs. Surgery is often necessary for treatment of invasive anisakiasis. With the increase in popularity of eating lightly cooked or raw fish dishes, the number of cases of anisakiasis may be expected to increase. Images PMID:2670191

Trichuris trichiura in a post-Colonial Brazilian mummy.

PubMed

Bianucci, Rafaella; Torres, Eduardo J Lopes; Santiago, Juliana M F Dutra; Ferreira, Luis F; Nerlich, Andreas G; Souza, Sheila Maria Mendonça de; Giuffra, Valentina; Chieffi, Pedro Paulo; Bastos, Otilio Maria; Travassos, Renata; Souza, Wanderley de; Araújo, Adauto

2015-02-01

Trichuris trichiura is a soil-transmitted helminth which is prevalent in warm, moist, tropical and subtropical regions of the world with poor sanitation. Heavy whipworm can result either in Trichuris dysenteric syndrome - especially in children - or in a chronic colitis. In heavy infections, worms can spread proximally and may cause ileitis. Here we provide first microscopic evidence for a T. trichiura adult worm embedded in the rectum of a post-Colonial Brazilian adult mummy. During Colonial and post-Colonial times, many European chroniclers described a parasitic disease named Maculo whose symptomatology coincides with heavy helminthiasis. Based on our findings and on comparison of ancient textual evidence with modern description of heavy whipworm, we feel confident in considering that the two syndromes are expressions of the same pathological condition.

Trichuris trichiura in a post-Colonial Brazilian mummy

PubMed Central

Bianucci, Rafaella; Torres, Eduardo J Lopes; Santiago, Juliana MF Dutra; Ferreira, Luis F; Nerlich, Andreas G; de Souza, Sheila Maria Mendonça; Giuffra, Valentina; Chieffi, Pedro Paulo; Bastos, Otilio Machado; Travassos, Renata; de Souza, Wanderley; Araújo, Adauto

2015-01-01

Trichuris trichiura is a soil-transmitted helminth which is prevalent in warm, moist, tropical and subtropical regions of the world with poor sanitation. Heavy whipworm can result either in Trichuris dysenteric syndrome - especially in children - or in a chronic colitis. In heavy infections, worms can spread proximally and may cause ileitis. Here we provide first microscopic evidence for a T. trichiura adult worm embedded in the rectum of a post-Colonial Brazilian adult mummy. During Colonial and post-Colonial times, many European chroniclers described a parasitic disease named Maculo whose symptomatology coincides with heavy helminthiasis. Based on our findings and on comparison of ancient textual evidence with modern description of heavy whipworm, we feel confident in considering that the two syndromes are expressions of the same pathological condition. PMID:25742276

Hla-B genotype in Japanese patients with Crohn's disease.

PubMed

Kinouchi, Yoshitaka; Matsumoto, Keisuke; Negoro, Kenichi; Takagi, Sho; Takahashi, Seiichi; Hiwatashi, Nobuo; Shimosegawa, Tooru

2003-10-01

The HLA-B gene is one of the susceptibility genes for inflammatory bowel disease. Previous association studies of HLA-B showed several associated alleles and haplotypes of HLA-B in patients with ulcerative colitis, and among the associated alleles HLA-B*52 is well known to be strongly associated with ulcerative colitis in Japanese patients. However, there are no convincing reports about HLA-B including the B*52 allele in patients with Crohn's disease. The purpose of this study was to determine if HLA-B, especially the B*52 allele, confers susceptibility to Crohn's disease or determines the disease phenotype of Crohn's disease. A total of 195 patients with Crohn's disease (49 ileitis, 106 ileocolitis, 34 colitis, 6 uncertain) and 185 healthy controls were studied in this case-controlled study. All patients and healthy controls were Japanese. Genotyping of the HLA-B gene was performed by a polymerase chain reaction, sequence-specific primer that can classify the gene into 23 allele groups. Allele frequencies were compared between patients with Crohn's disease and healthy controls with chi-squared test using a 2 x 2 contingency table. P value was corrected by the number of allele groups (n = 23) observed in the Japanese population or the number of clinical subgroups. Corrected P values of <0.05 were considered to be statistically significant. Before the correction for multiple testing, B*4001 and B*44 were associated with patients with Crohn's disease, positively and negatively, respectively. However, after the correction there were no significant differences in any HLA-B alleles between patients with Crohn's disease and healthy controls. In the subgroup analysis according to clinical phenotypes (disease location, anal lesion, age at diagnosis, need for surgery), none of the HLA-B alleles except B*52 showed any disease phenotype-genotype associations. The allele frequency of B*52 in the colitis type (16.2 percent; corrected P = 0.011) was significantly higher than that in the combined group of the ileitis (7.1 percent) and ileocolitis (5.2 percent) types. These results demonstrated that HLA-B did not confer overall susceptibility to Crohn's disease in Japan, but the B*52 allele may affect the location of the disease.

An Outbreak of Yersinia enterocolitica in a Captive Colony of African Green Monkeys (Chlorocebus aethiops sabaeus) in the Caribbean

PubMed Central

Soto, Esteban; Griffin, Matt; Verma, Ashutosh; Castillo-Alcala, Fernanda; Beierschmitt, Amy; Beeler-Marfisi, Janet; Arauz, Maziel; Illanes, Oscar

2013-01-01

Yersinia enterocolitica is a zoonotic gram-negative pathogen that causes mesenteric lymphadenitis, terminal ileitis, acute gastroenteritis, and septicemia in domestic animals and primates. In 2012, 46 captive African green monkeys (Chlorocebus aethiops sabaeus) died during an outbreak of acutely fatal enteric disease over a period of 1 mo on the island of St Kitts. The affected monkeys presented with a history of mucohemorrhagic diarrhea, marked dehydration, and depression. Fifteen bacterial isolates were recovered from the spleen, liver, and lungs of affected monkeys. All isolates were identified as Y. enterocolitica by biochemical analysis and sequence comparison of the 16S rRNA gene. Phenotypic and genotypic analysis of the recovered isolates revealed homogeneity among the recovered bacteria, and all isolates gave a random amplified polymorphic DNA pattern resembling that given by genotype D under serotypes O:7,8. This outbreak represents the first isolation and characterization of Y. enterocolitica as the causative agent of fatal enteric disease in primates in the Caribbean. PMID:24210021

Lactocepin secreted by Lactobacillus exerts anti-inflammatory effects by selectively degrading proinflammatory chemokines.

PubMed

von Schillde, Marie-Anne; Hörmannsperger, Gabriele; Weiher, Monika; Alpert, Carl-Alfred; Hahne, Hannes; Bäuerl, Christine; van Huynegem, Karolien; Steidler, Lothar; Hrncir, Tomas; Pérez-Martínez, Gaspar; Kuster, Bernhard; Haller, Dirk

2012-04-19

The intestinal microbiota has been linked to inflammatory bowel diseases (IBD), and oral treatment with specific bacteria can ameliorate IBD. One bacterial mixture, VSL#3, containing Lactobacillus, Bifidobacterium, and Streptococcus, was clinically shown to reduce inflammation in IBD patients and normalize intestinal levels of IP-10, a lymphocyte-recruiting chemokine, in a murine colitis model. We identified Lactobacillus paracasei prtP-encoded lactocepin as a protease that selectively degrades secreted, cell-associated, and tissue-distributed IP-10, resulting in significantly reduced lymphocyte recruitment after intraperitoneal injection in an ileitis model. A human Lactobacillus casei isolate was also found to encode lactocepin and degrade IP-10. L. casei feeding studies in a murine colitis model (T cell transferred Rag2(-/-) mice) revealed that a prtP-disruption mutant was significantly less potent in reducing IP-10 levels, T cell infiltration and inflammation in cecal tissue compared to the isogenic wild-type strain. Thus, lactocepin-based therapies may be effective treatments for chemokine-mediated diseases like IBD. Copyright © 2012 Elsevier Inc. All rights reserved.

Idelalisib-induced colitis and skin eruption mimicking graft-versus-host disease.

PubMed

Hammami, Muhammad Bader; Al-Taee, Ahmad; Meeks, Marshall; Fesler, Mark; Hurley, M Yadira; Cao, Dengfeng; Lai, Jin-Ping

2017-04-01

Idelalisib is a selective inhibitor of the delta isoform of phosphatidylinositol 3-kinase which was approved by the United States Federal Drug Administration in 2014 for the treatment of relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Drug-induced injury of the gastrointestinal tract is a relatively frequent but usually under-recognized disease entity. We report the case of a 56-year-old male with a history of relapsed follicular lymphoma status post allogenic bone marrow transplant who developed severe diarrhea with a skin eruption mimicking graft-versus-host disease (GVHD) 6 months after starting idelalisib. He underwent a colonoscopy demonstrating a grossly normal-appearing colon and terminal ileum. Biopsies taken during the procedure revealed mild active ileitis, colitis, and proctitis with frequent epithelial apoptosis, and focal intra-epithelial lymphocytosis. Skin biopsies revealed sub-acute spongiotic dermatitis suggestive of either contact dermatitis or an eczematous drug reaction. Symptoms were attributed to idelalisib given their resolution with withdrawal of the drug in conjunction with the skin and colonic biopsies. High clinical suspicion and awareness of the histological features of idelalisib-associated colitis is important to distinguish it from potential mimickers such as GVHD and infectious colitis.

Antigenic specificity and morphologic characteristics of Chlamydia trachomatis, strain SFPD, isolated from hamsters with proliferative ileitis.

PubMed

Fox, J G; Stills, H F; Paster, B J; Dewhirst, F E; Yan, L; Palley, L; Prostak, K

1993-10-01

Profound diarrhea associated with proliferating intestinal cells containing intraepithelial campylobacter-like organisms (ICLO) occurs in a variety of mammalian hosts, particularly swine and hamsters. Recently, intracellular bacteria were isolated from proliferative intestinal tissue of hamsters and propagated in intestine cell line 407. Oral inoculation of hamsters with cell culture lysates containing these organisms reproduced the disease in susceptible hamsters. In the present study, an intracellular bacterium from the INT 407 cell line was shown by a variety of techniques to be a member of the genus Chlamydia and has been designated Chlamydia sp. strain SFPD. McCoy cells infected with Chlamydia sp. strain SFPD demonstrated bright fluorescent-stained intracytoplasmic inclusions when examined with fluorescein-labeled species-specific C. trachomatis monoclonal antibodies. The organism also reacted to fluorescein-labeled polyclonal but not monoclonal ICLO "omega" antisera. Ultrastructural examination of the Chlamydia sp. strain SFPD from McCoy cells revealed electrondense elementary bodies and a less electron-dense reticulate-like body that was circular; both features are consistent in morphology to developmental forms of Chlamydia and do not conform to ICLO morphology. Molecular studies, 16S ribosomal sequence analysis, and sequencing of the outer membrane protein confirmed that the isolate is a C. trachomatis closely related to the mouse pneumonitis strain of C. trachomatis.

Pediatric surgery in Bangladesh.

PubMed

Bagwell, C E; Shandling, B

1986-09-01

Bangladesh, although a small country of only 55,000 square miles, is the world's eighth most populous nation, and its 90 million inhabitants occupy a land of harsh economic conditions. One half of this dense population is children, 90% of whom suffer from parasitic infestations, 10% are affected with neonatal tetanus, and one half are severely malnourished. Health care resources are scarce with one physician and hospital bed for about every 10,000 persons. A 1-month stay in Bangladesh at the Dhaka Shishu Hospital, made possible by the Canadian Association of Paediatric Surgeons, afforded an invaluable opportunity to be involved in Pediatric Surgery in such a setting. During the month, over 40 major pediatric surgical procedures were performed, including sequestrectomy, drainage of parietal wall abscess, and resection of massive neoplasms. Many unusual pathologic conditions, not commonly seen in Western countries, were encountered including canker otis, tuberculous ileitis, and ascaris-induced small bowel obstruction. In the setting of widespread malnutrition and limited diagnostic aids, appropriate surgical treatment remains crucial in many serious childhood conditions. Awareness of some of the more unusual infections and parasites seen in Third World nations is of great importance to Western surgeons due to increased travel and immigration and for a perspective on diseases rarely seen in more affluent countries.

[Septic shock Fusobacterium necrophorum from origin gynecological at complicated an acute respiratory distress syndrome: a variant of Lemierre's syndrome].

PubMed

Huynh-Moynot, Sophie; Commandeur, Diane; Danguy des Déserts, Marc; Drouillard, Isabelle; Leguen, Patrick; Ould-Ahmed, Mehdi

2011-01-01

We report a case of a female patient of 47 years old who presents in a state of septic shock with acute insufficient respiratory complicated with syndrome of acute respiratory distress, together with a list of abdominal pain and polyarthralgia too. In her case of medical history, it is retained that she has had a intra-uterine device since 6 years without medical follow up. The initial thoraco-abdomino-pelvic scan shows a left ovarian vein thrombosis, as well as the opaqueness alveolus diffused interstitiel bilaterally and an aspect of ileitis. The IUD is taken off because of sudden occuring of purulent leucorrhoea. This results in a clinical and paraclinical improvement, whereas aminopenicillin was administered to the patient since 1 week. The microbiological blood test allows to put in evidence Fusobacterium necrophorum found in a blood culture and is sensitive to the amoxicilline-acide clavulanique and metronidazole. Isolation of this bacteria, classically found in Lemierre's syndrome, allowed to explain the multilfocalization of the symtoms and the list of pain. The whole concerns about a variant of Lemierre's syndrom: a state of septic shock secondary then caused by the anaerobic Gram negative bacilli, which is a commensal bacteria of the female genital tractus, complicated of septic emboli typical.

Malignant peritoneal mesothelioma and Crohn disease.

PubMed

Butnor, Kelly J; Pavlisko, Elizabeth N; Sporn, Thomas A; Roggli, Victor L

2017-03-01

Mesothelial reaction simulating peritoneal diffuse malignant mesothelioma (MM) has been reported in the setting of Crohn ileitis. To our knowledge, peritoneal MM arising in patients with inflammatory bowel disease (IBD) has not been reported. The purpose of this study is to report the clinicopathological characteristics of patients with peritoneal MM and IBD. A database of approximately 3800 MM was reviewed for cases of MM in patients with IBD. Three patients (0.08%) with peritoneal MM and Crohn disease (CD) were identified, including two women and one man ranging in age from 56 to 65 years. All had a long-standing history of diarrhoea and an established diagnosis of CD of 3 years or greater duration. Two had epithelial MM and one had biphasic MM. Only one had documented asbestos exposure. Peritoneal MM occurs rarely in patients with IBD, but interestingly, has only been observed in the setting of CD and not in patients with ulcerative colitis. Chronic inflammation has been associated with the development of MM in rare instances and these three cases suggest that CD with transmural inflammation may also be a precursor. The precise role of CD-related transmural inflammation in the carcinogenesis of peritoneal MM remains to be determined. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Lassa fever presenting as acute abdomen: a case series.

PubMed

Dongo, Andrew E; Kesieme, Emeka B; Iyamu, Christopher E; Okokhere, Peter O; Akhuemokhan, Odigie C; Akpede, George O

2013-04-19

Lassa fever, an endemic zoonotic viral infection in West Africa, presents with varied symptoms including fever, vomiting, retrosternal pain, abdominal pain, sore-throat, mucosal bleeding, seizures and coma. When fever and abdominal pain are the main presenting symptoms, and a diagnosis of acute abdomen is entertained, Lassa fever is rarely considered in the differential diagnosis, even in endemic areas. Rather the diagnosis of Lassa fever is suspected only after surgical intervention. Therefore, such patients often undergo unnecessary surgery with resultant delay in the commencement of ribavirin therapy. This increases morbidity and mortality and the risk of nosocomial transmission to hospital staff. We report 7 patients aged between 17 months and 40 years who had operative intervention for suspected appendicitis, perforated typhoid ileitis, intussuception and ruptured ectopic pregnancy after routine investigations. All seven were post-operatively confirmed as Lassa fever cases. Four patients died postoperatively, most before commencement of ribavirin, while the other three patients eventually recovered with appropriate antibiotic treatment including intravenous ribavirin. Surgeons working in West Africa should include Lassa fever in the differential diagnosis of acute abdomen, especially appendicitis. The presence of high grade fever, proteinuria and thrombocytopenia in patients with acute abdomen should heighten the suspicion of Lassa fever. Prolonged intra-operative bleeding should not only raise suspicion of the disease but also serve to initiate precautions to prevent nosocomial transmission.

Lassa fever presenting as acute abdomen: a case series

PubMed Central

2013-01-01

Lassa fever, an endemic zoonotic viral infection in West Africa, presents with varied symptoms including fever, vomiting, retrosternal pain, abdominal pain, sore-throat, mucosal bleeding, seizures and coma. When fever and abdominal pain are the main presenting symptoms, and a diagnosis of acute abdomen is entertained, Lassa fever is rarely considered in the differential diagnosis, even in endemic areas. Rather the diagnosis of Lassa fever is suspected only after surgical intervention. Therefore, such patients often undergo unnecessary surgery with resultant delay in the commencement of ribavirin therapy. This increases morbidity and mortality and the risk of nosocomial transmission to hospital staff. We report 7 patients aged between 17 months and 40 years who had operative intervention for suspected appendicitis, perforated typhoid ileitis, intussuception and ruptured ectopic pregnancy after routine investigations. All seven were post-operatively confirmed as Lassa fever cases. Four patients died postoperatively, most before commencement of ribavirin, while the other three patients eventually recovered with appropriate antibiotic treatment including intravenous ribavirin. Surgeons working in West Africa should include Lassa fever in the differential diagnosis of acute abdomen, especially appendicitis. The presence of high grade fever, proteinuria and thrombocytopenia in patients with acute abdomen should heighten the suspicion of Lassa fever. Prolonged intra-operative bleeding should not only raise suspicion of the disease but also serve to initiate precautions to prevent nosocomial transmission. PMID:23597024

Pulmonary co-infection with nocardia species and nontuberculous mycobacteria mimicking miliary tuberculosis in a patient with Crohn's disease under combined immunosuppressive therapy.

PubMed

Weber, Marko; Rüddel, Jessica; Bruns, Tony; Pletz, Mathias W; Stallmach, Andreas

2018-06-01

Nocardiosis is a rare infection caused by ubiquitous soil-born, acid-resistant, Gram-positive bacteria that can be life-threatening in immunocompromised patients. Originally usually diagnosed in HIV-positive patients, only few cases have been reported in patients on immunosuppressive therapy for inflammatory bowel disease or rheumatologic disorders. We present a case of a 32-year-old man who was treated with infliximab, prednisolone, and azathioprine for severe terminal ileitis. Although the clinical status improved under triple immunosuppressive therapy, weight loss, weakness, and fatigue persisted. Laboratory studies revealed iron deficiency anemia, hypalbuminemia and raised inflammatory markers. Chest computed tomography scan showed multiple pulmonary nodules and a large cavity in the left upper lobe (segment 3a). Empiric tuberculostatic therapy was introduced for suspected miliary tuberculosis but stopped for lack of clinical improvement and negative tuberculosis tests (interferon-gamma release assay, microscopy, polymerase chain reaction). Finally, the diagnosis of pulmonary nocardiosis with concomitant pulmonary Mycobacterium avium infection was confirmed microbiologically, and the patient was treated with high-dose co-trimoxazole, clarithromycin, ethambutol, and rifampicin for 12 months.This case report underlines the increased risk of severe and rare infections like nocardiosis with combination immunosuppressive therapy and the necessity for thorough diagnostic screening for opportunistic infection. Although long-term antibiotic treatment for nocardiosis is mandatory, the optimal timing to restart immunosuppressive therapy remains ambiguous. © Georg Thieme Verlag KG Stuttgart · New York.

An open-label pilot study of granulocyte colony-stimulating factor for the treatment of severe endoscopic postoperative recurrence in Crohn's disease.

PubMed

Dejaco, Clemens; Lichtenberger, Conny; Miehsler, Wolfgang; Oberhuber, Georg; Herbst, Friedrich; Vogelsang, Harald; Gangl, Alfred; Reinisch, Walter

2003-01-01

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) promoted healing of Crohn's disease (CD)-like intestinal lesions in chronic granulomatous disease and glycogen storage disease Ib, both characterized by defective neutrophil functions. We performed a prospective, open-label pilot study with rhG-CSF for the treatment of CD. Five patients with clinically inactive CD, but with severe endoscopic ileitis within 1 year after intestinal resection and ileocolonic anastomosis, received 300 microg of rhG-CSF (Filgrastim; Neupogen) subcutaneously, three times weekly for a total of 12 weeks. Safety was evaluated by assessment of clinical and laboratory data and disease activity. The primary parameter of efficacy was complete mucosal healing, as defined by the Rutgeerts score. Anti-inflammatory mediators were repeatedly measured during treatment. All patients completed the protocol in clinical remission. In 1 subject transient headache resolved after halving the rhG-CSF dosage. Complete mucosal healing was observed in 2 patients: in 1 patient after 12 weeks of therapy and in 1 patient 9 months after treatment cessation. In a single patient, closure of an anovaginal and of a perianal fistula was noted. Neutrophil counts and interleukin-1 receptor antagonist and soluble tumor necrosis factor receptor p55 and p75 levels were found to be increased during drug administration. rhG-CSF seems to be safe, well tolerated, and might provide efficacy in CD. Copyright 2003 S. Karger AG, Basel

Unexpected findings after surgery for suspected appendicitis rarely change treatment in pediatric patients; Results from a cohort study.

PubMed

Gorter, Ramon R; van Amstel, Paul; van der Lee, Johanna H; van der Voorn, Patick; Bakx, Roel; Heij, Hugo A

2017-08-01

To determine if non-operative treatment is safe in children with acute appendicitis, we evaluated the incidence of unexpected findings after an appendectomy in children, and the influence they have on subsequent treatment. A historical cohort study (January 2004-December 2014) was performed including children, aged 0-17 years, who underwent an appendectomy for the suspicion of acute appendicitis. Patients were divided based upon histopathological examination. Unexpected findings were reviewed, as well as the subsequent treatment plan. In total 484 patients were included in this study. In the overall group, unexpected findings were noted in 10 (2.1%) patients of which two patients intra-operatively with a non-inflamed appendix (Ileitis terminalis N=1 and ovarian torsion N=1) and in 8 patients on histopathological examination. The latter group consisted of 4 patients with concomitant simple appendicitis (parasitic infection N=3 and Walthard cell rest N=1), two with concomitant complex appendicitis (carcinoid N=1 and parasitic infection N=1) and two patients with a non-inflamed appendix (endometriosis N=1 and parasitic infection N=1). Treatment was changed in 4 patients (<1%). Results from this study corroborate the safety of non-operative strategy for acute simple appendicitis, as the occurrence of unexpected findings was low, with extremely few necessary changes of the treatment plan because of serious findings. Prognosis study. Level 2 (retrospective cohort study). Copyright © 2017 Elsevier Inc. All rights reserved.

Sphingosine-1-phosphate receptor-1 (S1P1) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease

PubMed Central

Karuppuchamy, Thangaraj; Behrens, En-hui; González-Cabrera, Pedro; Sarkisyan, Gor; Gima, Lauren; Boyer, Joshua D.; Bamias, Giorgos; Jedlicka, Paul; Veny, Marisol; Clark, David; Peach, Robert; Scott, Fiona; Rosen, Hugh; Rivera-Nieves, Jesús

2016-01-01

The sphingosine-1-phosphate receptor-1 (S1P1) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. Here we examine the cell subsets that express S1P1 in intestine using S1P1-eGFP mice, the regulation of S1P1 expression in lymphocytes after administration of DSS, after colitis induced by transfer of CD4+CD45RBhi cells and by crossing a mouse with TNF-driven ileitis with S1P1-eGFP mice. We then assayed the expression of enzymes that regulate intestinal S1P levels, and the effect of FTY720 on lymphocyte behavior and S1P1 expression. We found that not only T and B cells express S1P1, but also dendritic (DC) and endothelial cells. Furthermore, chronic but not acute inflammatory signals increased S1P1 expression, while the enzymes that control tissue S1P levels in mice and humans with IBD were uniformly dysregulated, favoring synthesis over degradation. Finally, we observed that FTY720 reduced T cell velocity and induced S1P1 degradation and retention of naïve but not effector T cells. Our data demonstrate that chronic inflammation modulates S1P1 expression and tissue S1P levels and suggests that the anti-inflammatory properties of S1PR agonists might not be solely due to their lymphopenic effects, but also due to potential effects on DC migration and vascular barrier function. PMID:27049060

A case report of unexpected pathology within an incarcerated ventral hernia.

PubMed

Kane, Erica D; Bittner, Katharine R; Bennett, Michelle; Romanelli, John R; Seymour, Neal E; Wu, Jacqueline J

2017-01-01

Incidence of hernial appendicitis is 0.008%, most frequently within inguinal and femoral hernias. Up to 2.5% of appendectomy patients are found to have Crohn's disease. Elucidating the etiology of inflammation is essential for directing management. A 51-year-old female with achondroplastic dwarfism, multiple cesarean sections, and subsequent massive incisional hernia, presented with ruptured appendicitis within her incarcerated hernia. She underwent diagnostic laparoscopy, appendectomy, intra-abdominal abscess drainage, and complete reduction of ventral hernia contents. She developed a nonhealing colocutaneous fistula, causing major disruptions to her daily life. She elected to undergo hernia repair with component separation for anticipated lack of domain secondary to her body habitus. Her operative course consisted of open abdominal exploration, adhesiolysis, colocutaneous fistula repair, ileocolic resection and anastomosis, and hernia repair with bioresorbable mesh. She tolerated the procedure well. Unexpectedly, ileocolic pathology demonstrated chronic active ileitis, diagnostic of Crohn's disease. Only two cases of hernial Crohn's appendicitis have been reported, both within Spigelian hernias. Appendiceal inflammation inside a hernia sac may be attributed to ischemia from extraluminal compression of the hernia neck. This case demonstrates a rare presentation of multiple concurrent surgical disease processes, each of which impact the patient's treatment plan. This is the first report of incisional hernia appendicitis with nonhealing colocutaneous fistulas secondary to Crohn's. It is a lesson in developing a differential diagnosis of an inflammatory process within an incarcerated hernia and management of the complications related to laparoscopic hernial appendectomy in a patient with undiagnosed Crohn's disease. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prevalence of inflammatory bowel disease related dysplasia and cancer in 1500 colonoscopies from a referral center in northwestern Greece.

PubMed

Katsanos, Konstantinos H; Stamou, Paraskevi; Tatsioni, Athina; Tsianos, Vasileios E; Zoumbas, Stefanos; Kavvadia, Spyridoula; Giga, Anna; Vagias, Ioannis; Christodoulou, Dimitrios K; Tsianos, Epameinondas V

2011-02-01

To report on the prevalence of inflammatory bowel disease (IBD) related intestinal dysplasia and cancer in northwestern Greece. Single referral center retrospective study. The policy among all gastroenterologists of the area regarding medical treatment, patient follow up and bowel surveillance strategies including risk factors is the same. We analyzed 1494 colonoscopies from 696 consecutive IBD patients (494 UC). The follow up time [median, IQR] was 16 [8-23] years and the age at diagnosis was 28 [21-49] years. The number of patient years at risk was 16.219. Disease location for UC was: pancolitis 761 (59%), left sided colitis 455 (35%), and proctitis 69 (6%). Disease location for CD was: colitis 142 (66%), ileitis 45 (22%) and ileocolitis 21 (10%). Disease activity was in remission in 1240 (83%) of them. In total, 498 (72%) patients were on mesalazine, 169(24%) on immunosuppression and 29 (4%) on biologicals. Biopsies were taken randomly in 1429 (96%) endoscopies and were targeted in 65 (4%) of them. We recorded 69 (9.4%) cases with dysplasia and 10 (1.4%) cases with intestinal cancer (9 in UC). No difference was found for dysplasia and cancer in patients who followed up for 10-20 years or for more than 20 years. The prevalence of dysplasia and cancer is increased in UC compared to CD but the prevalence of high-grade dysplasia is comparatively low. Intestinal cancer prevalence is increasing after the first decade and then practically remains stable. Copyright © 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Sphingosine-1-phosphate receptor-1 (S1P1) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease.

PubMed

Karuppuchamy, T; Behrens, E-H; González-Cabrera, P; Sarkisyan, G; Gima, L; Boyer, J D; Bamias, G; Jedlicka, P; Veny, M; Clark, D; Peach, R; Scott, F; Rosen, H; Rivera-Nieves, J

2017-01-01

The sphingosine-1-phosphate receptor-1 (S1P 1 ) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. Here, we examine the cell subsets that express S1P 1 in intestine using S1P 1 -eGFP mice, the regulation of S1P 1 expression in lymphocytes after administration of dextran sulfate sodium (DSS), after colitis induced by transfer of CD4 + CD45RB hi cells, and by crossing a mouse with TNF-driven ileitis with S1P 1 -eGFP mice. We then assayed the expression of enzymes that regulate intestinal S1P levels, and the effect of FTY720 on lymphocyte behavior and S1P 1 expression. We found that not only T and B cells express S1P 1 , but also dendritic (DC) and endothelial cells. Furthermore, chronic but not acute inflammatory signals increased S1P 1 expression, while the enzymes that control tissue S1P levels in mice and humans with inflammatory bowel disease (IBD) were uniformly dysregulated, favoring synthesis over degradation. Finally, we observed that FTY720 reduced T-cell velocity and induced S1P 1 degradation and retention of Naïve but not effector T cells. Our data demonstrate that chronic inflammation modulates S1P 1 expression and tissue S1P levels and suggests that the anti-inflammatory properties of S1PR agonists might not be solely due to their lymphopenic effects, but also due to potential effects on DC migration and vascular barrier function.

Role of damage control enterostomy in management of children with peritonitis from acute intestinal disease.

PubMed

Ameh, Emmanuel A; Ayeni, Michael A; Kache, Stephen A; Mshelbwala, Philip M

2013-01-01

Intestinal anastomosis in severely ill children with peritonitis from intestinal perforation, intestinal gangrene or anastomotic dehiscence (acute intestinal disease) is associated with high morbidity and mortality. Enterostomy as a damage control measure may be an option to minimize the high morbidity and mortality. This report evaluates the role of damage control enterostomy in the treatment of these patients. A retrospective review of 52 children with acute intestinal disease who had enterostomy as a damage control measure in 12 years. There were 34 (65.4%) boys and 18 (34.6%) girls aged 3 days-13 years (median 9 months), comprising 27 (51.9%) neonates and infants and 25 (48.1%) older children. The primary indication for enterostomy in neonates and infants was intestinal gangrene 25 (92.6%) and perforated typhoid ileitis 22 (88%) in older children. Enterostomy was performed as the initial surgery in 33 (63.5%) patients and as a salvage procedure following anastomotic dehiscence in 19 (36.5%) patients. Enterostomy-related complications occurred in 19 (36.5%) patients, including 11 (21.2%) patients with skin excoriations and eight (15.4%) with hypokalaemia. There were four (7.7%) deaths (aged 19 days, 3 months, 3½ years and 10 years, respectively) directly related to the enterostomy, from hypokalaemia at 4, 12, 20 and 28 days postoperatively, respectively. Twenty other patients died shortly after surgery from their primary disease. Twenty of 28 surviving patients have had their enterostomy closed without complications, while eight are awaiting enterostomy closure. Damage-control enterostomy is useful in management of severely ill children with intestinal perforation or gangrene. Careful and meticulous attention to fluid and electrolyte balance, and stoma care, especially in the first several days following surgery, are important in preventing morbidity and mortality.

A requirement for the Vgamma1+ subset of peripheral gammadelta T cells in the control of the systemic growth of Toxoplasma gondii and infection-induced pathology.

PubMed

Egan, Charlotte E; Dalton, Jane E; Andrew, Elizabeth M; Smith, Judith E; Gubbels, Marc-Jan; Striepen, Boris; Carding, Simon R

2005-12-15

gammadelta T cells are a diverse population of T cells that are widely distributed and are a common feature of pathogen-induced immune responses. It is not clear, however, whether different populations of gammadelta T cells have specific functions, and what factors determine the functional properties of individual populations. A murine model of peroral Toxoplasma gondii infection was used to determine the contribution Vgamma1+ intestinal intraepithelial lymphocytes (IELs) vs systemic Vgamma1+ T cells make to the acute and chronic stages of the host immune response, and whether the macrophage cytocidal activity of Vgamma1+ T cells described in bacterial infections is seen in other, unrelated infectious disease models. In response to oral infection with virulent type 1 or avirulent type II strains of T. gondii, TCR-delta-/- mice rapidly developed severe ileitis. In contrast, in mice deficient in Vgamma1+ T cells and IELs and wild-type mice, inflammation was delayed in onset and less severe. The protective effect of (Vgamma1-) IELs to Toxoplasma infection was unrelated to their cytolytic and cytokine (Th1)-producing capabilities. Systemic Vgamma1+ T cells were shown to play an essential role in limiting parasite growth and inflammation in peripheral tissues and, in particular, in the CNS, that was associated with their ability to efficiently kill parasite-elicited and infected macrophages. These findings suggest that macrophage cytocidal activity of Vgamma1+ T cells may be a universal feature of pathogen-induced immune responses and that microenvironmental factors influence the involvement and function of gammadelta T cells in the host response to infection.

Expert opinion: experience with 6-mercaptopurine in the treatment of inflammatory bowel disease.

PubMed

Korelitz, Burton I

2013-05-28

Arbitrarily, modern day treatment of inflammatory bowel disease begins with the introduction of immunosuppressives for ulcerative colitis. Clinical improvement with sulfasalazine had been meaningful but modest. Treatment with adrenocorticotropic hormone and corticosteroids led to clinical responses never before realized but it took much too long to recognize that they were not capable of maintaining remission, that adverse reactions were subtle but potentially devastating and that some other agent would be necessary to capitalize on their transient advantage. This of course was true in the treatment of Crohn's disease as well. Not much was ever made of the role of sulfasalazine for Crohn's disease, but with the severing of the diazobond and the elimination of the sulphur component, the 5-aminosalacylic acid (5-ASA) products clearly led to clinical improvement, especially in cases of Crohn's colitis and those with ileitis where the 5-ASA product was released in the terminal ileum and more proximal in the small bowel as well as in ulcerative colitis. The induction of remission was first demonstrated by 6-mercaptopurine (6-MP) with case reports and uncontrolled trials in patients with ulcerative colitis, but its placebo controlled trial for Crohn's disease firmly established its role in inducing remission. No subsequent trial has confirmed its similar role for ulcerative colitis, but nevertheless clinicians know well that 6-MP works at least as well and probably more effectively for ulcerative colitis than for Crohn's disease. What changes have taken place utilizing 6-MP in the management of inflammatory bowel disease since its introduction in the 1960's and 1970's and its trial for Crohn's disease published in the New England Journal of Medicine in 1980?

Expert opinion: Experience with 6-mercaptopurine in the treatment of inflammatory bowel disease

PubMed Central

Korelitz, Burton I

2013-01-01

Arbitrarily, modern day treatment of inflammatory bowel disease begins with the introduction of immunosuppressives for ulcerative colitis. Clinical improvement with sulfasalazine had been meaningful but modest. Treatment with adrenocorticotropic hormone and corticosteroids led to clinical responses never before realized but it took much too long to recognize that they were not capable of maintaining remission, that adverse reactions were subtle but potentially devastating and that some other agent would be necessary to capitalize on their transient advantage. This of course was true in the treatment of Crohn’s disease as well. Not much was ever made of the role of sulfasalazine for Crohn’s disease, but with the severing of the diazobond and the elimination of the sulphur component, the 5-aminosalacylic acid (5-ASA) products clearly led to clinical improvement, especially in cases of Crohn’s colitis and those with ileitis where the 5-ASA product was released in the terminal ileum and more proximal in the small bowel as well as in ulcerative colitis. The induction of remission was first demonstrated by 6-mercaptopurine (6-MP) with case reports and uncontrolled trials in patients with ulcerative colitis, but its placebo controlled trial for Crohn’s disease firmly established its role in inducing remission. No subsequent trial has confirmed its similar role for ulcerative colitis, but nevertheless clinicians know well that 6-MP works at least as well and probably more effectively for ulcerative colitis than for Crohn’s disease. What changes have taken place utilizing 6-MP in the management of inflammatory bowel disease since its introduction in the 1960’s and 1970’s and its trial for Crohn’s disease published in the New England Journal of Medicine in 1980? PMID:23716977

Role of Gut Inflammation in Altering the Monocyte Compartment and Its Osteoclastogenic Potential in HLA-B27-Transgenic Rats.

PubMed

Ansalone, Cecilia; Utriainen, Lotta; Milling, Simon; Goodyear, Carl S

2017-09-01

To investigate the relationship between intestinal inflammation and the central and peripheral innate immune system in the pathogenesis of HLA-B27-associated spondyloarthritis using an HLA-B27-transgenic (B27-Tg) rat model. The myeloid compartment of the blood and bone marrow (BM) of B27-Tg rats, as well as HLA-B7-Tg and non-Tg rats as controls, was evaluated by flow cytometry. Plasma from rats was assessed by enzyme-linked immunosorbent assay for levels of CCL2 and interleukin-1α (IL-1α). Rats were treated with antibiotics for 4 weeks, and the myeloid compartment of the blood and BM was evaluated by flow cytometry. The osteoclastogenic potential of BM-derived cells from antibiotic-treated rats, in the presence or absence of tumor necrosis factor (TNF), was evaluated in vitro. B27-Tg rats had substantially higher numbers of circulating Lin-CD172a+CD43 low monocytes as compared to control animals, and this was significantly correlated with higher levels of plasma CCL2. Antibiotic treatment of B27-Tg rats markedly reduced the severity of ileitis, plasma levels of CCL2 and IL-1α, and number of BM and blood Lin-CD172a+CD43 low monocytes, a cell subset shown in the present study to have the greatest in vitro osteoclastogenic potential. Antibiotic treatment also prevented the TNF-dependent enhancement of osteoclastogenesis in B27-Tg rats. Microbiota-dependent intestinal inflammation in B27-Tg rats directly drives the systemic inflammatory and bone-erosive potential of the monocyte compartment. © 2017, American College of Rheumatology.

Polysaccharides derived from Ganoderma lucidum fungus mycelia ameliorate indomethacin-induced small intestinal injury via induction of GM-CSF from macrophages.

PubMed

Nagai, Kenta; Ueno, Yoshitaka; Tanaka, Shinji; Hayashi, Ryohei; Shinagawa, Kei; Chayama, Kazuaki

2017-10-01

Non-steroidal anti-inflammatory drugs often cause ulcers in the human small intestine, but few effective agents exist to treat such injury. Ganoderma lucidum Karst, also known as "Reishi" or "Lingzhi", is a mushroom. We previously reported that a water-soluble extract from G. lucidum fungus mycelia (MAK) has anti-inflammatory effects in murine colitis induced by trinitrobenzene sulfonic acid, and induction of granulocyte macrophage colony-stimulating factor (GM-CSF) by MAK may provide anti-inflammatory effects. However, its effects on indomethacin-induced small intestinal injuries are unknown. The present study investigated the preventative effects of MAK via immunological function and the polysaccharides from MAK on indomethacin-induced ileitis in mice. Peritoneal macrophages (PMs) were stimulated in vitro with MAK and adoptively transferred to C57BL/6 mice intraperitoneally, which were then given indomethacin. Intestinal inflammation was evaluated after 24h. We performed in vivo antibody blockade to investigate the preventive role of GM-CSF, which derived from PMs stimulated with MAK. We then used PMs stimulated with MAK pre-treated by pectinase in an adoptive transfer assay to determine the preventive role of polysaccharides. Indomethacin-induced small intestinal injury was inhibited by adoptive transfer of PMs stimulated in vitro with MAK. In this transfer model, pre-treatment with anti-GM-CSF antibody but not with control antibody reversed the improvement of small intestinal inflammation by indomethacin. Pectinase pretreatment impaired the anti-inflammatory effect of MAK. PMs stimulated by MAK appear to contribute to the anti-inflammatory response through GM-CSF in small intestinal injury induced by indomethacin. The polysaccharides may be the components that elicit the anti-inflammatory effect. Copyright © 2017 Elsevier Inc. All rights reserved.

Smooth Muscle Hyperplasia/Hypertrophy is the Most Prominent Histological Change in Crohn's Fibrostenosing Bowel Strictures: A Semiquantitative Analysis by Using a Novel Histological Grading Scheme.

PubMed

Chen, Wenqian; Lu, Cathy; Hirota, Christina; Iacucci, Marietta; Ghosh, Subrata; Gui, Xianyong

2017-01-01

The simplistically and ambiguously termed 'fibrostenosis' of bowel is a hallmark of severe Crohn's disease [CD] and a major contributor to medical treatment failure. Non-invasive imaging assessment and novel medical therapy targeting this condition are under investigation, which particularly requires a better understanding of the underlying histological basis. We analysed 48 patients with stricturing Crohn's ileitis or/and colitis that required surgical resection. The most representative sections of the fibrostenotic, non-stenotic and uninvolved regions were reviewed for histological analysis. For each layer of bowel wall (mucosa including muscularis mucosae [MU], submucosa [SM], muscularis propria [MP], subserosal adventitia [SS]), histological abnormalities were evaluated individually, including active and chronic inflammation, fibrosis, smooth muscle hyperplasia or hypertrophy, neuronal hypertrophy and adipocyte proliferation. A novel semiquantitative histological grading scheme was created. The most significant histopathological features characterizing the stricturing intestines were smooth muscle hyperplasia of SM, hypertrophy of MP and chronic inflammation. The muscular alteration was predominant in all layers. The overall muscular hyperplasia/hypertrophy was positively correlated with chronic inflammation and negatively correlated with fibrosis, whereas SM muscular hyperplasia was also associated with MU active inflammation. Similar changes, to a lesser extent, occurred in the adjacent non-stenotic inflamed bowel as well. In CD-associated 'fibrostenosis', it is the smooth muscle hyperplasia/hypertrophy that contributes most to the stricturing phenotype, whereas fibrosis is less significant. The 'inflammation-smooth muscle hyperplasia axis' may be the most important in the pathogenesis of Crohn's strictures. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Hypothalamic digoxin, hemispheric chemical dominance, and inflammatory bowel disease.

PubMed

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-09-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. It was considered pertinent to assess the pathway in inflammatory bowel disease (ulcerative colitis and regional ileitis). Since endogenous digoxin can regulate neurotransmitter transport, the pathway and the related cascade were also assessed in individuals with differing hemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. All the patients with inflammatory bowel disease were right-handed/left hemispheric dominant by the dichotic listening test. The following parameters were measured in patients with inflammatory bowel disease and in individuals with differing hemispheric dominance: (1) plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; (2) tryptophan/tyrosine catabolic patterns; (3) free-radical metabolism; (4) glycoconjugate metabolism; and (5) membrane composition and RBC membrane Na+-K+ ATPase activity. Statistical analysis was done by ANOVA. In patients with inflammatory bowel disease there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these groups of patients. Inflammatory bowel disease is associated with an upregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This can contribute to immune activation, defective glycoprotein bowel antigen presentation, and autoimmunity and a schizophreniform psychosis important in its pathogenesis. The biochemical patterns obtained in inflammatory bowel disease is similar to those obtained in left-handed/right hemispheric dominant individuals by the dichotic listening test. But all the patients with peptic ulcer disease were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Inflammatory bowel disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

Interleukin 31 mediates MAP kinase and STAT1/3 activation in intestinal epithelial cells and its expression is upregulated in inflammatory bowel disease

PubMed Central

Dambacher, Julia; Beigel, Florian; Seiderer, Julia; Haller, Dirk; Göke, Burkhard; Auernhammer, Christoph J; Brand, Stephan

2007-01-01

Background/aim Interleukin 31 (IL31), primarily expressed in activated lymphocytes, signals through a heterodimeric receptor complex consisting of the IL31 receptor alpha (IL31Rα) and the oncostatin M receptor (OSMR). The aim of this study was to analyse IL31 receptor expression, signal transduction, and specific biological functions of this cytokine system in intestinal inflammation. Methods Expression studies were performed by RT‐PCR, quantitative PCR, western blotting, and immunohistochemistry. Signal transduction was analysed by western blotting. Cell proliferation was measured by MTS assays, cell migration by restitution assays. Results Colorectal cancer derived intestinal epithelial cell (IEC) lines express both IL31 receptor subunits, while their expression in unstimulated primary murine IEC was low. LPS and the proinflammatory cytokines TNF‐α, IL1β, IFN‐γ, and sodium butyrate stimulation increased IL31, IL31Rα, and OSMR mRNA expression, while IL31 itself enhanced IL8 expression in IEC. IL31 mediates ERK‐1/2, Akt, STAT1, and STAT3 activation in IEC resulting in enhanced IEC migration. However, at low cell density, IL31 had significant antiproliferative capacities (p<0.005). IL31 mRNA expression was not increased in the TNFΔARE mouse model of ileitis but in inflamed colonic lesions compared to non‐inflamed tissue in patients with Crohn's disease (CD; average 2.4‐fold increase) and in patients with ulcerative colitis (UC; average 2.6‐fold increase) and correlated with the IL‐8 expression in these lesions (r = 0.564 for CD; r = 0.650 for UC; total number of biopsies analysed: n = 88). Conclusion IEC express the functional IL31 receptor complex. IL31 modulates cell proliferation and migration suggesting a role in the regulation of intestinal barrier function particularly in intestinal inflammation. PMID:17449633

Impact of budesonide on liver function tests and gut inflammation in patients with primary sclerosing cholangitis and ileal pouch anal anastomosis.

PubMed

Navaneethan, Udayakumar; Venkatesh, Preethi G K; Bennett, Ana E; Patel, Viral; Hammel, Jeffrey; Kiran, Ravi P; McCullough, Arthur J; Shen, Bo

2012-06-01

Budesonide has been studied in patients with primary sclerosing cholangitis (PSC). This study was designed to evaluate the efficacy of oral budesonide on liver function tests in patients with PSC and pouchitis associated with ileal pouch-anal anastomosis (IPAA). The study group consisted of 18 pouch patients with underlying ulcerative colitis (UC) and PSC who were treated with 9 mg daily of budesonide for their underlying pre-pouch ileitis and pouchitis for 1-3 months followed by 3-6 mg maintenance for another 9 months. Demographic and clinical variables were analyzed. The mean age was 39.4±12.4 years (range, 21-59 years). There was no significant change in aspartate aminotransferase (AST) [median (interquartile range) (IQR) 32 (25, 43.8) vs. 35.5 (25.5, 53), p=0.35], alanine aminotransferase (ALT) [37.5 (25.5, 49.5) vs. 40 (30, 84.3), p=0.29], alkaline phosphatase [142.5 (98.5, 264.5) vs. 126 (94.3, 189.5), p=0.35], serum bilirubin [0.7 (0.4, 1.3) vs., 0.6 (0.4, 1.6), p=0.13] or albumin levels [4.3 (3.9, 4.4) vs. 4.2 (3.8, 4.4), p=0.22] at the end of the treatment period (1 year). The revised Mayo Risk Score did not change significantly and three patients required evaluation for liver transplantation during treatment. There was a significant improvement in the endoscopy subscores in the afferent limb and pouch after a year of budesonide treatment (p=0.001). Oral budesonide appears to have no impact on liver function tests in pouch patients with PSC. However it significantly improved afferent limb and pouch inflammation in IPAA patients. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Probiotic Lactobacillus-induced improvement in murine chronic inflammatory bowel disease is associated with the down-regulation of pro-inflammatory cytokines in lamina propria mononuclear cells

PubMed Central

Matsumoto, S; Hara, T; Hori, T; Mitsuyama, K; Nagaoka, M; Tomiyasu, N; Suzuki, A; Sata, M

2005-01-01

IL-6/STAT-3 signals play key roles in inflammatory bowel disease (IBD). It is known that Lactobacillus casei strain Shirota (LcS) improves inflammatory disorders. This study aimed to elucidate the effect of LcS on murine chronic IBD and to clarify the mechanism. We focused the inhibitory effect of LcS on the production of IL-6 in lipopolysaccharide (LPS)-stimulated large intestinal lamina propria mononuclear cells (LI-LPMC) isolated from mice with chronic colitis and in RAW264·7 cells in vitro. We also determined in vivo the effect of LcS on murine chronic IBD models induced with dextran sodium sulphate and SAMP1/Yit mice. Finally, we examined the cellular determinants of LcS for the down-regulation of IL-6 secretion by LI-LPMC, RAW264·7 cells and peripheral blood mononuclear cells (PBMC) derived from patients with ulcerative colitis (UC). LcS, but not other strains of Lactobacillus, inhibited the production of IL-6 in LPS-stimulated LI-LPMC and RAW264·7 cells, down-regulating the nuclear translocation of NF-κB. The LcS-diet-improved murine chronic colitis is associated with the reduction of IL-6 synthesis by LI-LPMC. LcS also improved chronic ileitis in SAMP1/Yit mice. The release of IL-6 in vitro in LPS-stimulated LI-LPMC, RAW 264·7 cells and UC-PBMC was inhibited by a polysaccharide-peptidoglycan complex (PSPG) derived from LcS. This probiotic-induced improvement in murine chronic inflammatory bowel disease is associated with the down-regulation of pro-inflammatory cytokines such as IL-6 and IFN-γ production in LPMC. Therefore, LcS may be a useful probiotic for the treatment of human inflammatory bowel disease. PMID:15932502

Anal skin tags in inflammatory bowel disease: new observations and a clinical review.

PubMed

Bonheur, Jennifer L; Braunstein, Jared; Korelitz, Burton I; Panagopoulos, Georgia

2008-09-01

The association between intestinal Crohn's disease (CD) and specific perianal abnormalities called anal skin tags (AST) has been recognized but not well defined. Skin tags have been classified into 2 types: 1) raised, broad, or narrow, single or multiple, soft or firm, and painless, often referred to as "elephant ears"; or 2) edematous, hard, often cyanotic, tender or not, and typically arising from a healed anal fissure, ulcer, or hemorrhoid. The aims of this study were to i) better characterize those skin tags identified by the term "elephant ears" and differentiate them from other types of AST; ii) compare their prevalence in patients with CD and ulcerative colitis (UC); iii) observe the relationship of the skin tags to the location of the primary bowel disease; and iv) to discuss the value of these typical AST in making an early diagnosis of CD. Photographs of all AST were taken when present at lower endoscopy in 170 consecutive patients with inflammatory bowel disease (IBD) seen in the private office of the senior investigator and Lenox Hill Hospital. Data was gathered with respect to major differences between the 2 types of AST. The location of the primary bowel disease for these patients was obtained from an extensive IBD computer database and review of details from charts. Specific features of AST were described and served to favor type 1 versus type 2. AST were found more frequently in patients with CD (75.4%) as compared to patients with UC (24.6%), confirming previous observations that they are more diagnostic of CD (P = 0.005). Subset analysis revealed a trend with a greater incidence of AST in patients with colitis (46.9%) as compared to patients with ileitis (36.7%) and ileocolitis (16.3%) (P = 0.067). We provide photographs with the most characteristic features of AST and attempt to separate elephant ears (type 1) from less typical AST (type 2) in CD. Our study confirms previous reports that AST are more commonly found in association with CD as compared with UC and more so in the presence of disease limited to the colon as compared to disease elsewhere in the bowel. Our observations support the diagnostic significance of AST heralding the diagnosis of CD when they are discovered on physical exam, especially in young people with diarrhea, abdominal pain, and/or growth retardation.

Genetic Factors Interact With Tobacco Smoke to Modify Risk for Inflammatory Bowel Disease in Humans and Mice.

PubMed

Yadav, Pankaj; Ellinghaus, David; Rémy, Gaëlle; Freitag-Wolf, Sandra; Cesaro, Anabelle; Degenhardt, Frauke; Boucher, Gabrielle; Delacre, Myriam; Peyrin-Biroulet, Laurent; Pichavant, Muriel; Rioux, John D; Gosset, Philippe; Franke, Andre; Schumm, L Philip; Krawczak, Michael; Chamaillard, Mathias; Dempfle, Astrid; Andersen, Vibeke

2017-08-01

The role of tobacco smoke in the etiology of inflammatory bowel disease (IBD) is unclear. We investigated interactions between genes and smoking (gene-smoking interactions) that affect risk for Crohn's disease (CD) and ulcerative colitis (UC) in a case-only study of patients and in mouse models of IBD. We used 55 Immunochip-wide datasets that included 19,735 IBD cases (10,856 CD cases and 8879 UC cases) of known smoking status. We performed 3 meta-analyses each for CD, UC, and IBD (CD and UC combined), comparing data for never vs ever smokers, never vs current smokers, and never vs former smokers. We studied the effects of exposure to cigarette smoke in Il10 -/- and Nod2 -/- mice, as well as in Balb/c mice without disruption of these genes (wild-type mice). Mice were exposed to the smoke of 5 cigarettes per day, 5 days a week, for 8 weeks, in a ventilated smoking chamber, or ambient air (controls). Intestines were collected and analyzed histologically and by reverse transcription polymerase chain reaction. We identified 64 single nucleotide polymorphisms (SNPs) for which the association between the SNP and IBD were modified by smoking behavior (meta-analysis Wald test P < 5.0 × 10 -5 ; heterogeneity Cochrane Q test P > .05). Twenty of these variants were located within the HLA region at 6p21. Analysis of classical HLA alleles (imputed from SNP genotypes) revealed an interaction with smoking. We replicated the interaction of a variant in NOD2 with current smoking in relation to the risk for CD (frameshift variant fs1007insC; rs5743293). We identified 2 variants in the same genomic region (rs2270368 and rs17221417) that interact with smoking in relation to CD risk. Approximately 45% of the SNPs that interact with smoking were in close vicinity (≤1 Mb) to SNPs previously associated with IBD; many were located near or within genes that regulate mucosal barrier function and immune tolerance. Smoking modified the disease risk of some variants in opposite directions for CD vs UC. Exposure of Interleukin 10 (il10)-deficient mice to cigarette smoke accelerated development of colitis and increased expression of interferon gamma in the small intestine compared to wild-type mice exposed to smoke. NOD2-deficient mice exposed to cigarette smoke developed ileitis, characterized by increased expression of interferon gamma, compared to wild-type mice exposed to smoke. In an analysis of 55 Immunochip-wide datasets, we identified 64 SNPs whose association with risk for IBD is modified by tobacco smoking. Gene-smoking interactions were confirmed in mice with disruption of Il10 and Nod2-variants of these genes have been associated with risk for IBD. Our findings from mice and humans revealed that the effects of smoking on risk for IBD depend on genetic variants. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

A comprehensive review and update on Crohn's disease.

PubMed

Gajendran, Mahesh; Loganathan, Priyadarshini; Catinella, Anthony P; Hashash, Jana G

2018-02-01

The term inflammatory bowel disease (IBD) refers principally to two major categories of chronic relapsing inflammatory intestinal disorders: Crohn's disease (CD) and ulcerative colitis (UC). In the United States, it is currently estimated that about 1.5 million people suffer from IBD, causing considerable suffering, mortality and economic loss every year. Yet the cause of IBD is unknown, and until we understand more, prevention or cure will not be possible. There is a lot of variation in the incidence and prevalence of CD based on geographic region, environment, immigrant population, and ethnic groups. The annual incidence of CD in North America is reported to be 3.1-20.2 per 100,000 with a prevalence of 201 per 100,000 population. Based on the epidemiological, genetic and immunological data, CD is considered to be a heterogeneous disorder with multifactorial etiology in which genetics and environment interact to manifest the disease. Several genes have been studied so for with respect to CD, but thus far the strong and replicated associations have been identified with NOD2, IL23R and ATG16L1 genes. The risk factors implicated with CD include smoking, low fiber- high carbohydrate diet, altered microbiome and medications such as non-steroidal anti-inflammatory drugs. CD is typically characterized by transmural inflammation of the intestine and could affect any part of the gastrointestinal tract from mouth to perianal area. In terms of distribution of the disease 25% of the patients have colitis only, 25% is ileitis only and 50% have ileocolitis. The Montreal classification is based on the age at diagnosis (<16, 17-40, > 40), disease location (Ileal, colonic, Ileocolonic) and the disease behavior (nonstricturing/nonpenetrating, stricturing, penetrating). The key features for diagnosing CD comprises a combination of radiographic, endoscopic and pathological findings demonstrating focal, asymmetric, transmural or granulomatous features. Abdominal Computed tomography (CT) enterography is the most preferred first-line radiologic study used in the assessment of small bowel CD. The diagnostic accuracy of magnetic resonance enterography/enteroclysis is similar to that of CT scans and also prevents exposure to ionizing radiation. Endoscopic scores are considered to be the gold standard tool to measure the activity of CD and they are used more commonly in the clinical trials to measure the efficacy of various drugs on inducing and maintaining mucosal healing. The most common scoring systems used to measure clinical disease activity include Crohn's Disease Activity Index (CDAI), HBI- Harvey-Bradshaw index (HBI), short inflammatory bowel disease questionnaire (SIBDQ) and Lehmann score. Management of Crohn's disease has been seen as an evolving challenge owing to its widely heterogeneous manifestations, overlapping characteristics with other inflammatory disorders, often elusive extraintestinal manifestations and uncertain etiology. Therapeutic interventions are tailored to address symptomatic response and subsequent tolerance of the intervention. Chronology of treatment should favor treatment dose acute disease or "induction therapy", followed by maintenance of adequate response or remission, i.e. "maintenance therapy". The medications which are highly effective in inducing remission include steroids and Tumor Necrosis Factor (TNF) inhibitors. Medications used to maintain remission include 5-aminosalicyclic acid products, immunomodulators (Azathioprine, 6-mercaptopurine, methotrexate) and TNF inhibitors (infliximab, adalimumab, certolizumab and golimumab). Surgical interventions like bowel resection, stricturoplasty or drainage of abscess is required in up to two thirds of CD patients during their lifetime. The most common indications for surgical resection are medically refractory disease, perforation, persisting or recurrent obstruction, abscess not amenable to percutaneous drainage, intractable hemorrhage, dysplasia or cancer. Endoscopic recurrence in postoperative CD patients, as defined by Rutgeers score i2-i4 occur in 30-90% of the patients at the neoterminal ileum within 12 months of surgery and almost universally by 5 years. Treating CD requires a comprehensive care team including the patient, primary care provider, and gastroenterologist. In summary CD is a chronic inflammatory condition with a remitting and relapsing course primarily affecting relatively younger population with significant socioeconomic effects. Copyright © 2018 Mosby, Inc. All rights reserved.

[Ultrasonography in acute pelvic pain].

PubMed

Kupesić, Sanja; Aksamija, Alenka; Vucić, Niksa; Tripalo, Ana; Kurjak, Asim

2002-01-01

Acute pelvic pain may be the manifestation of various gynecologic and non-gynecologic disorders from less alarming rupture of the follicular cyst to life threatening conditions such as rupture of ectopic pregnancy or perforation of inflamed appendix. In order to construct an algorithm for differential diagnosis we divide acute pelvic pain into gynecologic and non-gynecologic etiology, which is than subdivided into gastrointestinal and urinary causes. Appendicitis is the most common surgical emergency and should always be considered in differential diagnosis if appendix has not been removed. Apart of clinical examination and laboratory tests, an ultrasound examination is sensitive up to 90% and specific up to 95% if graded compression technique is used. Still it is user-depended and requires considerable experience in order to perform it reliably. Meckel's diverticulitis, acute terminal ileitis, mesenteric lymphadenitis and functional bowel disease are conditions that should be differentiated from other causes of low abdominal pain by clinical presentation, laboratory and imaging tests. Dilatation of renal pelvis and ureter are typical signs of obstructive uropathy and may be efficiently detected by ultrasound. Additional thinning of renal parenchyma suggests long-term obstructive uropathy. Ruptured ectopic pregnancy, salpingitis and hemorrhagic ovarian cysts are three most commonly diagnosed gynecologic conditions presenting as an acute abdomen. Degenerating leiomyomas and adnexal torsion occur less frequently. For better systematization, gynecologic causes of acute pelvic pain could be divided into conditions with negative pregnancy test and conditions with positive pregnancy test. Pelvic inflammatory disease may be ultrasonically presented with numerous signs such as thickening of the tubal wall, incomplete septa within the dilated tube, demonstration of hyperechoic mural nodules, free fluid in the "cul-de-sac" etc. Color Doppler ultrasound contributes to more accurate diagnosis of this entity since it enables differentiation between acute and chronic stages based on analysis of the vascular resistance. Hemorrhagic ovarian cysts may be presented by variety of ultrasound findings since intracystic echoes depend upon the quality and quantity of the blood clots. Color Doppler investigation demonstrates moderate to low vascular resistance typical of luteal flow. Leiomyomas undergoing degenerative changes are another cause of acute pelvic pain commonly present in patients of reproductive age. Color flow detects regularly separated vessels at the periphery of the leiomyoma, which exhibit moderate vascular resistance. Although the classic symptom of endometriosis is chronic pelvic pain, in some patients acute pelvic pain does occur. Most of these patients demonstrate an endometrioma or "chocolate" cyst containing diffuse carpet-like echoes. Sometimes, solid components may indicate even ovarian malignancy, but if color Doppler ultrasound is applied it is less likely to obtain false positive results. One should be aware that pericystic and/or hillar type of ovarian endometrioma vascularization facilitate correct recognition of this entity. Pelvic congestion syndrome is another condition that can cause an attack of acute pelvic pain. It is usually consequence of dilatation of venous plexuses, arteries or both systems. By switching color Doppler gynecologist can differentiate pelvic congestion syndrome from multilocular cysts, pelvic inflammatory disease or adenomyosis. Ovarian vein thrombosis is a potentially fatal disorder occurring most often in the early postpartal period. Hypercoagulability, infection and stasis are main etiologic factors, and transvaginal color Doppler ultrasound is an excellent diagnostic tool to diagnose it. Acute pelvic pain may occur even in normal intrauterine pregnancy. This may be explained by hormonal changes, rapid growth of the uterus and increased blood flow. Ultrasound is mandatory for distinguishing normal intrauterine pregnancy from threatened or spontaneous abortion, ectopic pregnancy and other complications that may occur in patients with positive pregnancy test. Incomplete abortion is visualized as thickened and irregular endometrial echo with certain amount of intracavitary fluid. If applied, color Doppler ultrasound reveals low vascular resistance signals in richly perfused intracavitary area. Transvaginal sonography has high sensitivity and specificity in visualization of uterine and adnexal signs of ectopic pregnancy. Color Doppler examination may aid in detection of the peritrophoblastic flow. Furthermore, it facilitates detection of ectopic living embryo, tubal ring or unspecific adnexal tumor. Corpus luteum cysts and leiomyomas are another cause of pelvic pain during pregnancy, which can be correctly diagnosed by ultrasound. Detection of uterine dehiscence and rupture in patients with history of prior surgical intervention on uterine wall relies exclusively on correct ultrasound diagnosis. In patients with placental abruption sonographer detects hypoechoic complex representing either retroplacental hematoma, subchorionic hematoma or subamniotic hemorrhage. In closing, ultrasound has already become important and easily available tool which can efficiently recognize patients with possibly threatening conditions of different origins.