Inflammation Does Not Decrease Intraluminal pH in Chronic Inflammatory Bowel Disease

Intestinal inflammation may influenceintraluminal pH. Profiles of the gastrointestinal pHwere evaluated in 15 patients with active Crohn'sdisease of the ileocecal area. In addition, fivepatients with moderate (1) or severe (4) ulcerative colitiswere studied. Fifteen healthy subjects served ascontrols. Intraluminal pH of the different parts of thegastrointestinal tract was measured by a free-floating pH-sensitive telemetering capsule. A metalsphere was attached to the capsule for exactlocalization by a metal detector. Physiological patternsof pH were maintained throughout the gastrointestinaltract including the inflamed segments. Median pH inthe terminal ileum of the patients with Crohn's diseasewas 7.5 vs 7.7 and in the rectum in ulcerative colitis7.8 vs 7.2 in the controls. In conclusion, intraluminal pH is not decreased by inflammatory changes inCrohn's disease and ulcerative colitis, allowingeudragit-coated pH-controlled-release formulations ofmesalazine to dissolve in diseased areas also.     

Ulcerative colitis complicated by gastroduodenal lesions

A case of ulcerative colitis complicated with gastric and duodenal lesions is reported. The patient was a 17-year-old male who was admitted with bloody diarrhea and abdominal pain. Based on the endoscopic and histological findings of the colon, a diagnosis of ulcerative colitis was made. Upper gastrointestinal endoscopy showed multiple erosions and granular changes in the antral greater curvature of the stomach and descending portion of the duodenum. Histological examination of the stomach and duodenum revealed marked inflammatory cell infiltration and crypt abscesses. Clinically, the gastric and duodenal lesions did not respond to antiulcer drugs, but were alleviated by steroid. It was concluded that the pathogenesis of the gastric and duodenal lesions in this patient was similar to that of the colonic lesions of ulcerative colitis.     

Altered expression of innate immunity genes in different intestinal sites of children with ulcerative colitis

Background

Innate immunity has been very rarely investigated in ulcerative colitis and never in paediatrics. The present study was aimed at describing expression of innate immunity genes (NOD2, RIP2, α-defensins HD5 and HD6) in inflamed colon and in ileum of children with ulcerative colitis. Expression of TNFα and IL-1β was also analyzed.

Methods

15 children with ulcerative colitis (9 pancolitis, 6 left-sided colitis) and 10 control children were enrolled. mRNA and protein expressions were detected by real time PCR and western blot assays.

Results

NOD2, RIP2, IL-1β, TNFα expression levels were significantly increased in colonic mucosa of patients compared to controls (p < 0.01). These genes were also upregulated (p < 0.01) in the ileum of both pancolitis and left-sided colitis children. HD5 and HD6 were significantly upregulated (p < 0.01) in the inflamed colon of patients as well as in the ileum of those with pancolitis.

Conclusions

An increased mucosal expression of innate immunity genes was found in the inflamed colon of children with ulcerative colitis, outlining the role of the innate immune response in disease pathogenesis. Involvement of the ileum in ulcerative colitis suggests that an immune activation can also be established in intestinal sites classically uninvolved by the inflammation, carrying implications for the treatment and course of the disease.     

Gastroduodenal Crohn's disease - report of 4 cases and review of the literature

BACKGROUND: Crohn's disease can affect all the gastrointestinal tract, but gastroduodenal involvement is rarely seen (0.5 to 13%). OBJECTIVES: Report clinical, radiological and endoscopic findings and treatment of four patients with gastroduodenal Crohn's disease and review the literature. PATIENTS AND METHODS: Four patients (one male of 24 years old three females of 37, 66 and 74 years old) with epigastric pain, weight loss and low grade fever were referred to the University Hospitals of Federal University of Rio de Janeiro and Fluminese Federal University. Two had also mild intermittent diarrhea and arthritis/arthralgia and the third developed pyloric obstruction and received surgical treatment. Anemia was observed in only one (the young female). Barium x-ray studies showed aphthous ulcers in stomach and duodenum with distal ileum lesions and deformity in both. Upper gastrointestinal endoscopy revealed aphthous ulcers in stomach and geographic duodenal ulcers. Polypoid lesions and serpiginous ulcers within gastric antrum were observed in the young female. Colonoscopy was performed in two patients and disclosed an ulcerated ileitis in one and ulcerated pancolitis in other. Histopathology findings of biopsy specimens were inconclusive (granulomas were not found) and other causes of granulomatous disease were ruled out. Corticosteroids and proton pump inhibitors were started and two patients had their disease controlled. The other patient developed pyloric obstruction and had to be operated. CONCLUSIONS: Gastroduodenal Crohn's disease has distinct clinical, therapeutic and prognostic features. Advances in endoscopic methods and recognition of new histopathologic criteria for diagnosis have revealed an incidence higher than previously reported.     

Influence of Feces from Patients with Ulcerative Colitis on Butyrate Oxidation in Rat Colonocytes

An impaired oxidation of butyrate has beensuggested as a causative factor of ulcerative colitisand, moreover, agents present in colonic luminalcontents impair butyrate oxidation in both rat and human colonocytes. To evaluate the overall effect offeces on the production of CO₂ and ketonebodies from butyrate oxidation in rat colonocytes, fecalhomogenates from 10 healthy subjects and 10 patients with quiescent and 10 patients with activeulcerative colitis were sterile filtrated and added torat colonocytes incubated with 2, 4, and 10 mmol/literof stock butyrate, respectively. Addition of fecal filtrate from healthy subjects and patientswith quiescent and active ulcerative colitis tocolonocytes incubated with 2, 4, and 10 mmol/liter ofstock butyrate, respectively, tended to decrease theproduction of CO₂ from butyrate oxidation,whereas ketogenesis was unaffected. The decrease inCO₂ production was not explained by thesimultaneous addition of fecal short-chain fatty acids(SCFAs). However, a difference in the ability todecrease CO₂ production was not found betweenfiltrates from healthy subjects and patients withquiescent and active ulcerative colitis. In conclusion, feces from healthy subjects and patients withquiescent and active ulcerative colitis containinhibitor(s) of the production of CO₂ frombutyrate oxidation in colonocytes. However, a specific inhibitory effect of feces from patients withulcerative colitis on the production of CO₂could not be identified.     

Ulcerative Colitis Associated with Primary Biliary Cirrhosis

Primary biliary cirrhosis and ulcerative colitisare two diseases with many features of autoimmunity.Thirteen cases of coexistence of the two diseases havebeen reported in the literature so far. Patients are usually younger and more often males thanthe ordinary primary biliary cirrhosis patient, whilethe colitis is mild and easily controllable. In ahomogeneous population of 550,000 inhabitants of the island of Crete, 412 cases of ulcerativecolitis and 82 individuals with primary biliarycirrhosis or autoimmune cholangitis have beenidentified. In two cases, coexistence of the twodiseases was found. Immunological screening for AMA positivity in150 ulcerative colitis sera disclosed no further cases.Prevalence of primary biliary cirrhosis in ulcerativecolitis patients seems at least 30 times higher than in the general population in our area. Apossible immunological link between the two diseases isdiscussed.     

Nodular duodenitis involving CD8+ cell infiltration in patients with ulcerative colitis

BACKGROUND/AIMS: Limited efforts have been made to determine changes in the upper gastrointestinal tract in ulcerative colitis. The aim of this study was to analyze gastroduodenal lesions in patients with ulcerative colitis. METHODOLOGY: The endoscopical appearance of lesions in the duodenum and stomach was first examined. Biopsy specimens taken from 25 patients with ulcerative colitis, as well as 21 with Crohn's disease and 16 with nonspecific gastroduodenitis who had no Helicobacter pylori infection, were then evaluated by histology and immunohistochemistry for CD8, CD68 and HLA-DR. In ulcerative colitis patients, the HLA-phenotype was also analyzed by the standard NIH complement-dependent microlymphocyte toxicity assay. RESULTS: Endoscopically evident alteration of nodularity in the descending part of duodenum was prominent in ulcerative colitis and Crohn's disease, but not gastroduodenitis. Histological inflammatory change of the duodenal bulb in ulcerative colitis and Crohn's disease was mild as compared to gastroduodenitis cases. Endoscopic and histological change (redness and deformity of villi) in the duodenum were more prominent in ulcerative colitis patients with pancolitis than those with left-sided/proctitis. CD8+ cells infiltrating both the duodenum and stomach were increased in ulcerative colitis and Crohn's disease as compared to gastroduodenitis whereas focal perifoveolar accumulation of CD68+ cells and enhanced epithelial expression of HLA-DR were characteristic of Crohn's disease. Histopathological alteration in the duodenum was particularly prevalent in ulcerative colitis patients with HLA-DR4 and Cw1. CONCLUSIONS: Nodular, histologically mild duodenitis involving CD8+ cell infiltration, the severity of which positively correlates with the extent of colitis, is characteristic of ulcerative colitis.     

Ulcerative duodenitis accompanying ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon of unknown etiology. There are varied manifestations in the natural course of UC. However, duodenum is not generally considered a target organ of UC. Here, we report two patients with steroid-responsive ulcerative duodenitis with colitis that was consistent with UC, but not with Crohn's disease. We also reviewed six cases of ulcerative duodenitis with UC. Duodenal lesion with UC may be a more common phenomenon, although infrequently clinically manifested under steroid therapy. Upper gastrointestinal tract inflammation in UC warrants further studies to ascertain whether the duodenum is a target organ in UC, especially in steroid-free conditions.     

Diffuse gastroduodenitis associated with ulcerative colitis: Treatment by infliximab

Diffuse gastroduodenitis resembling ulcerative colitis in respect to macro‐ and microscopic findings occurs in ulcerative colitis, although it is rare. Reports of gastroduodenitis associated with ulcerative colitis treated with infliximab are rare. A 58‐year‐old man had tarry stool in March 2011. He had a history of ulcerative colitis that was diagnosed in 1984. He underwent subtotal colectomy in 1991. Endoscopy and radiography revealed diffuse friable mucosa throughout the duodenum and an ulcer in the middle of the descending portion, resulting in a narrow portion.In the stomach, numerous small aphthae were observed in the antrum. Biopsy specimens of the duodenum and antrum showed marked inflammatory cell infiltration in both areas and cryptitis in the duodenum. Standard induction therapy of infliximab was started in April. The ulcer in the descending portion became a scar without diffuse mucosal friability in September 2011.     

Simultaneous Ulcerative Colitis and Crohn's Disease

This report describes a patient with simultaneous Crohn's disease of the terminal ileum and ulcerative colitis of the left colon and rectum. Well documented cases of "mixed" ileocolitis are quite rare.     

Optimizing therapy in patients with pancolitis

Pancolitis affects approximately 20% to 40% of the total ulcerative colitis population and remains a therapeutic challenge for clinicians. Practitioners must focus on pancolitis when evaluating a patient for ulcerative colitis, because pancolitis is associated with more severe and fulminant disease and a higher rate of colorectal cancer and colectomy. It is imperative for clinicians to be knowledgeable in the clinical course, medications, and appropriate manner to induce and maintain clinical remission to prevent serious sequelae of the disease. The purpose of this article is to provide a review of the treatment of pancolitis for general gastroenterologists, because medical management decisions have life-long effects for this subgroup of patients.     

Ulcerative colitis and malignancy

Ulcerative colitis is associated with an increased risk for colorectal cancer. The increase is approximately six to ten times the expected in the general population. Disease duration and extension are the major risk factors. Concomitant primary sclerosing cholangitis is an additional independent risk factor. The relative risk is approximately 14.8 for patients with pancolitis while it is 1.7 for patients with disease restricted to the rectum. The risk increases rapidly after 20 years of disease evolution. Active treatment might decrease the risk. The increased cancer risk is a major problem for longterm management of patients with ulcerative colitis. It is the rationale for various surveillance programs and the search for dysplasia. Two major types of dysplasia must be distinguished in ulcerative colitis: sporadic adenomas and ulcerative colitis-associated dysplasia. Sporadic adenomas can be treated by simple polypectomy. The diagnosis of dypsplasia relies mainly on microscopic analysis of biopsy samples. Additional techniques, including flow cytometry and the search for DNA abnormalities and immunohistochemistry or molecular techniques looking for genetic defects can help to improve the diagnostic yield.     

Effects of Colectomy on Gallbladder Motility in Patients with Ulcerative Colitis

In order to gain insight into the possiblemechanisms involved in gallstone formation incolectomized ulcerative colitis patients, we studiedgallbladder motility by means of ultrasonography inthree groups of subjects: controls (N = 40) and ulcerativecolitis patients without (N = 30) and with (N = 20)colectomy. Impaired gallbladder emptying after a liquidfatty meal stimulus was observed in ulcerative colitis patients with colectomy compared with thoseobtained in ulcerative colitis patients withoutcolectomy and controls (P = 0.001). The maximumpercentage of gallbladder emptying also, wassignificantly lower (59.8%) than those seen in ulcerative colitispatients without colectomy (74.5%) and controls (77.8%)(P = 0.001). Diminished gallbladder emptying withensuing stasis might be a contributory factor to the increased prevalence of gallstones incolectomized patients.     

Changes in Bacterial Enzymes and PCR Profiles of Fecal Bacteria from a Patient with Ulcerative Colitis Before and After Antimicrobial Treatments

A 26-year-old female patient, suffering fromrecurrent attacks of ulcerative colitis accompanied byextraintestinal symptoms (erythema nodosum and pyodermagangrenosum), was evaluated for the effect of antibacterial agents on the intestinal bacteriaand their enzymatic activities. The enzymes were assayedboth at the onset of disease symptoms and aftertreatment with each of five drug regimens (fluconazole and cefadroxil, cefuroxime axetil andcestriaxone sodium, ciprofloxacin and cestriaxonesodium, ciprofloxacin alone, and ciprofloxacin,metronidazole, and cephalexin). The activities ofazoreductase, nitroreductase, oxidoreductase, glucuronidase, and sulfatasewere generally lower following all of the treatments,especially when ciprofloxacin was included. The DNA fromeach sample was amplified by PCR, using random primers. Profiles of amplified DNA on agarosegels showed different patterns, indicating differencesin the microflora before and after the antimicrobialtreatments. The clinical response to antibacterial therapy was consistent with the decreasedbacterial enzymatic activities and changes in themicrobial population. Ciprofloxacin, which wasassociated with the most dramatic falls in enzymaticactivity, also had the best clinical results. We concludethat intestinal bacteria and their enzymes playimportant roles in ulcerative colitis and thatpopulation changes can be monitored using PCRprofiles.     

Coagulation Systems and Neutrophils in the Activation of Plasma Contact and Active Phase of Ulcerative Colitis

We have shown that the contact (kallikrein-kinin) system is involved in the pathogenesis ofexperimental enterocolitis. We now investigateactivation of the contact and coagulation pathways,platelets, and neutrophils in active and inactiveulcerative colitis patients as compared to normalcontrols. In active ulcerative colitis patients, asignificant decrease of plasma prekallikrein, highmolecular weight kininogen, and C1 inhibitor levels was observedas compared with controls, as well as prekallikreinactivation on western blots. Significant elevation ofprothrombin fragment (F1 + 2), which indicates thrombin generation, and elastase-1-antitrypsincomplexes, reflecting neutrophil activation, were foundin patients with active disease. Plasmabeta-thromboglobulin, a marker of platelet activation,was elevated in both active and inactive disease and appearsto be a feature of ulcerative colitis. Activation ofcontact and coagulation pathways, as well asneutrophils, may mediate inflammation in the activephase of ulcerative colitis.     

Colonic Luminal Hydrogen Sulfide Is Not Elevated in Ulcerative Colitis

It has been proposed that the reduction inn-butyrate oxidation by colonic epithelial cellsobserved in ulcerative colitis may be related toexposure to reduced forms of sulfur derived fromdissimilatory sulfate reduction by luminal microflora. Thisstudy aims to compare stool sulfide concentrations incontrol and colitic subjects. Control subjects hadsignificant colorectal disease excluded by virtue of their selection. Patients with ulcerativecolitis were stratified by disease extent and activity,and by salicylate drug use. Stool sulfide was measuredusing a direct spectrophotometric method on NaOH (free sulfide) and zinc acetate (total sulfide)stool slurries. Fifteen control and 19 colitic subjectswere studied. There was no significant difference instool sulfide between control and colitic patients (free sulfide, control =0.52 (0.17), colitic0.45 (0.10), t = 0.36, P = 0.71, total sulfide, control1.33 (0.21), colitic 0.96 (0.15), t = 1.44, P = 0.16).Disease extent or activity did not significantlyinfluence stool sulfide. These results do not support aprimary etiologic role for luminal sulfide in ulcerativecolitis.     

Ulcerative colitis in Kuwait: a review of 90 cases

BACKGROUND: Chronic ulcerative colitis is a disease of unknown etiology. Its incidence is on the rise in various developing countries as has been reported in studies from South-East Asia and the Middle East. There seems to be significant differences in the pattern and the clinical course of this disease in our patient population. The aim of our study is to assess the incidence and the clinical course of the disease in Kuwait. METHODS: This is a retrospective study of cases identified over a period of 14 years (1985-1999). Three hundred forty-six patients were identified to have chronic ulcerative colitis. Ninety patients were interviewed for this study. RESULTS: Chronic ulcerative colitis is being identified with increasing frequency. Our local incidence was 2.8 per 100,000 persons per year. The disease was seen in both sexes with equal frequency. It peaks at the third decade of life, with no second peak observed in the sixth decade. The disease was of mild to moderate severity in 93% of the cases. The distribution of the disease in the colon showed pancolitis in 45%, left-sided colitis in 14%, proctosigmoiditis in 21% and proctitis in 20%. Arthritis and arthralgia were the most frequent extraintestinal manifestation seen in 31%. Perianal disease, although rare in ulcerative colitis, was seen in 8%. Of interest is the fact that over 14 years of follow-up, none of our patients developed high-grade dysplasia or colorectal cancer. Four patients required total colectomy mainly due to failure of medical therapy. CONCLUSIONS: Chronic ulcerative colitis is occurring with increasing frequency similar to that seen in Western countries. The disease observed in our patient population was of mild to moderate severity, with fewer complications than reported in Western countries. It peaks in the third decade with no second peak. None of our patients developed high-grade dysplasia or colorectal carcinoma.     

Role of Appendectomy and Tonsillectomy in Pathogenesis of Ulcerative Colitis

We wished to determine the effect ofappendectomy and tonsillectomy on the subsequent riskfor development of ulcerative colitis (UC). We conducteda case-control study at the University of OklahomaHospital and VA Medical Center gastroenterology clinics,as well as at the offices of private physicians.Subjects being followed for UC formed the study group.Patients being followed at Internal Medicine Associates of the University of Oklahoma clinics formedthe controls. We recorded the patient's name, age, sex,race, history of smoking, and history of appendectomy ortonsillectomy. The study group consisted of 193 patients, and there were 394 controls. Theprevalence of appendectomy was lower (17.8% vs 5.2%)among patients with UC (P < 0.01). The prevalence oftonsillectomy was similar in the two groups (20.6% vs 18.1%; P = NS). We conclude thatappendectomy is associated with a decreased risk forsubsequent development of ulcerative colitis.     

Interleukin-8 and Neutrophil Markers in Colonic Mucosa from Patients with Ulcerative Colitis

In this study, mediators of inflammation were characterized in colonic and terminal ileum mucosa from subjects with ulcerative colitis. We considered the role of two different chemotactic factors (interleukin-8 and leukotriene B4) and of myeloperoxidase in the pathology of inflammatory bowel disease. Serial biopsy specimens were taken at different sites, washed in 0.02 M phosphate/saline buffer, homogenized, and then sonically disrupted. In both the proximal and distal regions of the colonic mucosa of ulcerative colitis patients, there was a more than 10-fold increase in interleukin-8 levels over that in control subjects (> 300 pg/mg protein vs. 30 pg/mg protein in controls, p < or = 0.01). However, terminal ileum levels of interleukin-8 were the same in ulcerative colitis and control groups (150 pg/mg protein). There was also a 3- to 5-fold increase in leukotriene B4 levels and a several-fold increase in myeloperoxidase levels throughout the colonic mucosa in patients with ulcerative colitis. This study demonstrates that 1) interleukin-8 may have an immunoregulatory role in the pathogenesis of inflammatory bowel disease, and 2) interleukin-8, myeloperoxidase, and leukotriene B4 may be useful markers for the biochemical identification of inflammatory bowel disease.     

Controlled Trial of 4-ASA in Ulcerative Colitis

A six-week placebo-controlled trial of theefficacy and safety of 6 g per day of 4-aminosalicylicacid (4-ASA) was conducted in 30 subjects with mild tomoderately severe ulcerative colitis. Subjects were stratified into groups having distal (<60cm) or more extensive (>60 cm) disease. Diarrhea,bleeding, sigmoidoscopic and biopsy appearance, andphysician global assessment were scored to judgeefficacy. Safety was evaluated by monitoring untowardsymptoms and laboratory values. Median percentimprovement was significantly greater (P < 0.05) inthe 4-ASA 60-cm group (42.7%) than in the placebo 60-cmgroup (21.2%), but 4-ASA was not better than placebofor the 60-cm group or the total study group. Severedyspepsia (one subject), abnormal AST (transient infive, persistent in one) and elevated lipase without pancreatitis (six subjects) were noted. Thus 6g 4-ASA for six weeks was more effective than placebo inmild to moderate ulcerative colitis extending more than60 cm above the anus, but not in distal disease, and the drug was generally welltolerated.