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Demonstration of circulating immune complexes by the indirect leucocyte phagocytosis test in chronic inflammatory bowel disease. Relation to results of a standard complement consumption assay.

Circulating immune complexes were studied in untreated Crohn's disease (CD) and ulcerative colitis (UC) by leucocyte phagocytosis. Neutrophils from normal donors took up large immunoglobulin-containing inclusions from 14 of 15 CD sera, 3 of 15 UC sera (p less than 0.002) and from none of 15 reference sera from healthy volunteers (p less than 0.002). In contrast, inclusions could not be demonstrated on direct microscopic investigation. Our study confirms the presence of circulating immune complexes in Crohn's disease. Predominance of IgG-containing complexes in this condition is consistent with a mucosal origin. Discrepant results obtained by direct examination and by incubation of sera from patients with normal test neutrophils suggest a defective immune complex phagocytosis in CD. In consistency with this possibility, control experiments revealed a markedly decreased complex uptake by neutrophils of CD patients in vitro.

Antigen-Antibody Complex↗

[Therapeutic effect of methyl 5-aminosalicylate on experimental ulcerative colitis in rabbits].

Using the improved Kirsner model of ulcerative colitis in rabbits, we found that the therapeutic effect of methyl 5-amino salicylate hydrochloride (M-5-AS) was similar to that of sulfasalazine (salicylazosulfapyridine, SZ). The length of pathological damage and the range of diffuse ulcers were decreased in comparison with the control group (P less than 0.01, 0.05). Microscopically, tissue repairing at the regions of ulcers and proliferation in serolemma were noted, and the edema in muscular mesenchyme was less evident in the treated rabbits. M-5-AS completely inhibited the spontaneous contraction of rat stomach fundus strips and colon. The IC50 of the resting tone of the 2 tissues were 1.30 +/- 0.39 and 0.72 +/- 0.25 mmol/L, respectively. In addition, M-5-AS antagonized the contraction induced by human fresh semen. The results suggest that the therapeutic mechanism is related to the antagonism of prostaglandins in the inflammatory regions.

Aminosalicylic Acids↗

Sulphydryl blocker-induced rat colitis is ameliorated by intravenous injection of antibody to colonic surfactant-like particle.

A rat model of experimental colitis and jejunitis induced by iodoacetamide (IA), a sulphydryl blocker is accompanied by increased leukotriene, prostaglandin E2 (PGE2) generation, and nitric oxide synthase (NOS) activity. Rat small intestinal and colonic surfactant-like particles (SLP) that accumulate on the apical surface of mucosal cells have been identified and specific antibodies to them have been produced. The aim of this study was to evaluate a possible role of SLP in IA-induced colitis and jejunitis. Inflammation was induced in Sprague-Dawley rats either by intracolonic administration of 3% IA (0.1 ml) or by intrajejunal administration of 2% IA (0.1 ml). Antisera raised against either colonic SLP, pulmonary SP-A (a major protein associated with colonic SLP), or small intestinal SLP were injected into the tail vein of rats 48 h before, simultaneous with, or 24 h after IA administration. Rats were killed 2 or 10 days after IA was given, their colon or small intestine was isolated and rinsed, and a segment of colon (10 cm) or small bowel (30 cm) was weighed and processed for microscopy, NOS and myeloperoxidase (MPO) activities, and PGE2 generation. Intracolonic or jejunal IA resulted after 48 h in extensive macroscopic and microscopic damage, accompanied by increased segmental weight, MPO and NOS activity, and PGE2 generation. Colonic SLP antibody administration, either 48 h before or at the time of damage induction, significantly decreased macroscopic as well as microscopic damage, segmental weight, MPO activity, and PGE2 generation, but had no effect on NOS activity. Neither control sera nor antisera against SP-A had any protective effect, nor did injection of anti-colonic SLP antisera given 24 h after IA. Small bowel SLP antibody offered no protection against IA jejunitis. IA-induced colitis but not jejunitis is ameliorated by intravenous injection of SLP antibody by a mechanism yet to be determined. These data provide further evidence of a physiologic role for gastrointestinal SLP.

Animals↗

[Urgent ulcerative colitis: our experience].

The authors refer their experience in Urgent Ulcerative Colitis. They define the various clinical maniferstations and then specify the necessary elements for a corrent nosological arrangement. About diagnosis, their confirm the inconvenience of clinical examination like as colonscopy or an opaque clysma, giving their choice to other parameters, like as clinical, hematic (PCR), microscopic and cultural of the faeces, radiological (direct abdomen radiography; abdomino-pelvic echography; abdomino-pelvic TC, better if spiral), endoscopic (rectoscopy with minimal insufflation). They explain their guideline about medical therapy, the strategy adopted in relation to its duration, the protocol of evaluation during the administration period and the predictive sighs of its possible failure. After having precised the surgical indications, they stop a little about the timing of a surgical interventation, underlining its primary importance. In the range of a surgical strategy. They give their choice to the total colectomy with associated ioleostomy for its less incidence of complications and mortality versus proctocolectomy, reserving this last one to that cases with irreprensible rectal hemorragy, with preservation of the anal canal for a possible delayed ileo-anal anastomosis. They also think, at last, that after an Urgent Total Colectomy, the immediate ileo-rectum anastomosis could have an high risk of dehiscence of the anastomosis itself and so it must be reserved only to that selected cases which offer local and general guarantees of solidity of the anastomosis and it must be preferably done joinly whit a loop ileostomy at the bottom of the anastomosis itself.

Colectomy↗

Colitis reduces short-circuit current response to inflammatory mediators in rat colonic mucosa.

Inflammatory mediators may contribute to the diarrhea associated with colitis. Although the secretory action of such mediators is reported in normal tissue, there is little information regarding their effects on inflamed tissue. We examined the short-circuit current response (Isc) to these mediators, in mitomycin-C (MC)-induced colitis, a model with histological similarities to colitis in man. Rats were injected once with MC (3.25 mg/kg, intraperitoneally) or vehicle. The colons were removed three and seven days later and mounted, devoid of muscularis, in Ussing chambers for measurement of Isc, potential difference (PD), and resistance (Rt). MC-treated rats had diarrhea after three days, and microscopic studies revealed colonic inflammation. There were no significant differences in Rt, PD, and Isc between control and MC-treated tissues at three and seven days. Maximal increases in Isc to bradykinin, prostaglandin E1, carbachol, substance P, and serotonin were depressed at three and/or seven days after MC. The Isc response to theophylline was not affected. Theophylline activates secretion through an intracellular mechanism; the other agonists act by interaction with epithelial cell membranes. Therefore, the mechanism for the decreased Isc may result from uncoupling of receptors to second-messenger systems or desensitization of receptor-linked secretory mechanisms.

Alprostadil↗

Mesalamine capsules for treatment of active ulcerative colitis: results of a controlled trial. Pentasa Study Group.

The efficacy of a capsule formulation of mesalamine was assessed in 374 patients with mild to moderately active ulcerative colitis. Patients, stratified to pancolitis or left-sided disease, received either placebo or mesalamine at 1, 2, or 4 g daily for 8 wk. Efficacy was assessed using clinical improvement--physician global assessment, sigmoidoscopic index, biopsy score, trips to the toilet, and clinical symptoms (abdominal pain, urgency, stool consistency, and rectal bleeding)--and induction of remission (more stringent criteria for physician global assessment, sigmoidoscopic index, and biopsy score). For physician global assessment of treatment benefit, 79% and 84% of patients on the 2-g and 4-g doses of mesalamine, respectively, received treatment benefit, compared with 54% on placebo (p < or = 0.0002). For the physician global assessment of treatment success, both the 2-g and 4-g doses of mesalamine were superior to placebo (57% and 59% of patients, p = 0.0021 and 0.0012, respectively), compared with 36% on placebo. Both the 2-g and 4-g doses produced statistically significant macroscopic (endoscopic) improvement compared with placebo (p < 0.004). The 4-g dose also produced a statistically significant microscopic (histologic) improvement compared to placebo (p < 0.002). Significant improvement compared to placebo was also observed at 2 g and 4 g for the four clinical symptoms and trips to the toilet (p < or = 0.003). Oral mesalamine capsules were significantly superior to placebo for inducing remission, with 29% of patients at 2 g and 29% at 4 g achieving remission by physician global assessment, compared with 12% on placebo. Forty-four percent and 48% of patients receiving 2 g and 4 g of mesalamine, respectively, achieved remission by sigmoidoscopic index (p < 0.05), compared with 31% on placebo. Thirty-nine percent of patients at 4 g daily achieved microscopic remission, compared with 23% on placebo (p < 0.03). Treatment response was not affected by extent of disease or prior steroid or sulfasalazine therapy. These data suggest that controlled-release mesalamine capsules are a safe and effective monotherapy in doses of 2-4 g daily for treating mild to moderately active ulcerative colitis, as well as for inducing remission, regardless of prior oral steroid or sulfasalazine therapy or extent of disease.

Adult↗

Colobronchial fistula: a rare complication of Crohn's colitis.

A 29-yr-old white woman presented with chronic pneumonia in the left lower lobe and with left pleural effusion. She was known to have inflammatory bowel disease, but she was asymptomatic under maintenance treatment with 5-ASA. She received numerous antibiotic regimens according to susceptibility testing of microorganisms cultured from sputum and bronchial lavage and on an empiric basis was also given antituberculosis treatment, but there was no clinical improvement or change in the chest radiographic findings. Sputum was repeatedly examined and yielded, among other organisms, Clostridium inocuum, Enterobacter, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus aureus. On one microscopic examination of sputum, the presence of feculent material was suspected. A subsequent gastrografin enema revealed a cologastric and colobronchial fistula between the splenic flexture of the colon and the greater curve of the stomach and the bronchial system. Segmental resection of the colon and resection of the lower lobe of the left lung were performed. Histologic findings of the resected colon were consistent with Crohn's disease. After a long period of postoperative recovery, the patient returned to good general health and well-being. To our knowledge, a colobronchial fistula caused by Crohn's colitis has not been previously reported.

Adult↗

Pericrypt eosinophilic enterocolitis and chronic diarrhea.

An unusual pattern of eosinophilic infiltration around intestinal crypts was detected in mucosal biopsy specimens of 10 patients with chronic diarrhea, half of whom had evidence of systemic connective tissue disease. The median duration of symptoms was 11 months, and no other explanation for diarrhea could be determined in any case. The cellular infiltrate on biopsy specimens was present deep in the mucosa of small and large intestinal specimens, separating crypt bases from the muscularis mucosae and penetrating the latter. Consistent with the microscopic findings, surface mucosal appearance by endoscopy was uniformly normal. These histological features of colonic biopsy specimens were statistically differentiated from those of asymptomatic subjects (n = 8), subjects with diarrhea-predominant irritable bowel syndrome (n = 6), and subjects with collagenous colitis (n = 7) or lymphocytic colitis (n = 5). Diarrhea improved in five of seven subjects treated with oral prednisone or prednisone in conjunction with azathioprine (median follow-up period, 2.2 years). Histological changes on subsequent biopsy specimens correlated closely with symptomatic status. These findings strongly suggest that chronic diarrhea is related to this pericrypt eosinophilic enterocolitis, a pathological lesion often associated with features of systemic connective tissue disease. The disorder appears responsive to corticosteroid therapy in some cases.

Adrenal Cortex Hormones↗

Chemokine expression in IBD. Mucosal chemokine expression is unselectively increased in both ulcerative colitis and Crohn's disease.

Mucosal changes in inflammatory bowel disease (IBD) are characterized by ulcerative lesions accompanied by prominent cellular infiltrates in the bowel wall. Chemokines are chemotactic cytokines that are able to promote leukocyte migration to areas of inflammation and are also able to initiate cell activation events. They have recently been implicated in the pathophysiology of many disease states. The aim of this study was to detail the degree and distribution of specific chemokines, interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, -2, and -3, and macrophage inflammatory protein (MIP)-1alpha and -1beta, in IBD mucosa. Thirty-nine patients were included, ten controls, 20 ulcerative colitis (UC), and nine Crohn's disease (CD), with a range of disease activity. Colonic mucosal biopsies were collected from UC, CD, and control patients and embedded in glycol methacrylate. Two-micrometre-thick sections were cut and stained using immunohistochemistry for chemokine protein expression. Sections were analysed using a light microscope. Expression of all types of chemokine protein was detected in colonic mucosa from both control and IBD patients. Patterns of staining between IBD patients and controls differed significantly, but CD and UC patients demonstrated similar patterns of staining. Individual chemokine expression was found to be significantly up-regulated in IBD when patients were compared with the non-diseased group in all areas of the mucosal sections. Up-regulated chemokine expression correlated with increasing activity of the disease. It is concluded that human colonic chemokine expression is non-selectively up-regulated in IBD. The results supported the hypothesis that the degree of local inflammation and tissue damage in UC and CD is dependent on local expression of specific chemokines within IBD tissues.

Chemokine CCL2↗

Epithelial patchy necrosis in Crohn's disease.

Electron and light microscopic studies of the intestinal epithelium in Crohn's disease demonstrated localized areas of damage to the superficial epithelium, occurring without accompanying acute inflammation. In a blind study of rectal biopsy specimens from seven patients with Crohn's disease, four with ulcerative colitis, and four normal controls, this finding of patchy necrosis without acute inflammation was observed exclusively in four of the seven cases of Crohn's disease.

Biopsy↗

Xanthogranulomatous inflammation of the sigmoid colon: a case report.

A rare case of xanthogranulomatous inflammation of the sigmoid colon presenting as intestinal obstruction is reported. This is the first report of this lesion involving the large bowel which demonstrated the characteristic macroscopic and microscopic features. Though rare, xanthogranulomatous inflammation should be considered in patients presenting with large bowel obstruction.

Adipose Tissue↗

Clostridium butyricum, a probiotic derivative, suppresses dextran sulfate sodium-induced experimental colitis in rats.

Recent studies have suggested that probiotics or short chain fatty acids (SCFAs) exert a therapeutic effect on inflammatory bowel disease (IBD) patients. In a previous study, we demonstrated that Clostridium butyricum produces high levels of SCFAs in culture. In addition, a yogurt-based additive effectively masked, completely eliminating the unpleasant odor derived from the SCFAs. We recently reported that the oral administration of both high and low dose diets (50% w/w for 17 days and 5% w/w for 16 months, respectively) of the Clostridium butyricum derivative did not cause pathological abnormalities in rats. In the present study, we evaluated the effects of this product against dextran sulfate sodium (DSS)-induced experimental colitis in rats. Five-week-old male Wistar Hannover GALAS rats were given a mixture of a standard diet containing 3% (w/w) of DSS for 8 days. In the derivative-fed group, Clostridium butyricum derivative (20% w/w) with 0.1% (w/w) additive was also added to their diet. The control-fed group was given tap water (20% w/w) with 0.1% (w/w) additive. After 8 days, a laparotomy was performed, and macroscopic and microscopic inflammation scoring was determined. The Clostridium butyricum derivative effectively prevented bloody diarrhea. In addition, mucosal damage to the derivative-fed group was significantly reduced macroscopically compared to that of the control-fed group. The potential clinical efficacy of the Clostridium butyricum derivative in IBD patients is also discussed.

Administration, Oral↗

Multifocal colitis associated with an epidemic of chronic diarrhea.

An outbreak of a chronic diarrheal syndrome was detected between May and August 1987 in rural Henderson County, Illinois. Seventy-two individuals were affected. Epidemiological studies performed by the Center for Disease Control implicated the water of a local restaurant as the source of the outbreak. Five patients underwent a comprehensive evaluation. Their mean age was 51 years, and they had a mean of 12 watery stools daily (range, 6-40). Detailed microbiological evaluations failed to identify a pathological organism. Stool studies showed a mean stool weight of 392 g/24 h with a normal fat content. Results of all biochemical studies of serum were normal. Chemical analysis of stool water suggested a secretory diarrhea. Colonoscopy revealed patchy erythema, and light microscopic examination of colonic biopsy specimens revealed multifocal areas of acute inflammation in the superficial mucosa in 4 of 5 patients. Electron microscopy of the affected areas revealed no viral particles. After 2 years, all of our patients continued to experience chronic diarrhea. One patient agreed to a follow-up colonoscopy; histological abnormalities of the colonic mucosa persisted after 2 years. We speculate that an infectious process arising from a contaminated water system induced a chronic, secretory diarrhea characterized by multifocal colitis. This histological abnormality may serve as a marker of an infectious, chronic diarrhea.

Adolescent↗

[Cytomegalovirus infection of the gastrointestinal tract in patients with HIV-infection].

AIM: To study clinical and morphological characteristics of gastrointestinal cytomegalovirus (CMV) infection in HIV-infected subjects. MATERIAL AND METHODS: The examination of 70 HIV-infected subjects (all of them had secondary diseases, AIDS, CMV infection in the gastrointestinal tract; mean age 31.2 +/- 1.4 years) observed from 1993-2005 included conduction of flow cytofluorimetry (to assess immunity), esophagogastroduodenoscopy, colonoscopy, PCR (to assay CMV DNA in blood leukocytes), examination of biopsy and autopsy samples for CMV DNA and other pathogens of opportunistic diseases). There were 55 lethal outcomes. In autopsy, a total macroscopic and microscopic examination of the gastrointestinal tract was made. Serial histotopographic sections were studied with a wide spectrum of histological stains. RESULTS: CMV gastrointestinal lesion was diagnosed in 38.9% of 180 HIV-infected subjects who had stomatitis, pharyngitis, esophagitis, gastritis, enteritis, enterocolitis or colitis. Diagnostic criteria of viral lesion were high blood concentrations of CMV DNA, the presence of cytomegalocells, CMV DNA in biopsy or autopsy material. CONCLUSION: CMV infection manifested with severe pain, loss of weight, weakness, remitting fever. Gastrointestinal lesions were erosive-ulcerous or ulceronecrotic. The following pathogenetic chain of CMV infection course in the gastrointestinal tract was established: vasculitis--microcirculatory disorders--segmental ischemia--necrosis with inflammatory infiltration and CMV transformation of the cells--fibrosing--cicatricial transformation of the organ wall. Developing sclerosis due to CMV involvement of the intestine may promote cancer, but this should be proved in further studies. CMV gastrointestinal infection was successfully treated by cimeven (ganciclovir) and valcit (valganciclovir). The effect was achieved in 91% cases.

Adult↗

Histiocytic ulcerative colitis in a boxer. A case report.

A case of canine histiocytic ulcerative colitis, a disease of boxers, is here described. It appears that this disease has not been previously reported in Scandinavia. The diagnosis was established at necropsy of a 5-month-old boxer, which had shown bloody diarrhoea since the age of four weeks. Treatment with antibiotics had only given a temporary remission of the condition. Macroscopical findings included thickening of the wall of the descending colon and rectum, multiple ulcers in the rectocolonic mucosa and marked enlargement of the colonic lymph nodes. Microscopically the lesions were characterized by large accumulations of PAS-positive histiocytes, mixed with cells of the plasma cell type, in the mucosa and submucosa of the rectum and descending colon and in the colonic lymph nodes. The importance of using proctocolonoscopy and colon biopsy for the clinical diagnosis of this condition is stressed.

Animals↗

Electron microscope studies of experimental Entamoeba histolytica infection in the guinea pig. II. Early cellular and vascular changes accompanying invasion of the lamina propria.

Early cellular and vascular changes in response to invasion of lamina propria by Entamoeba histolytica were studied sequentially, at the ultrastructural level, in germfree guinea pigs inoculated intracecally with amebae and enteric flora derived from patients with acute amebic colitis. Approximately one week post-inoculation the animals developed acute colitis with mucosal invasion by trophic amebae. Although epithelial cells at the sites of amebic invasion showed progressive cytoplasmic changes and desquamation resulting in microerosions, most mesenchymal elements in the lamina propria appeared normal without cytopathic changes even when in direct contact with invading amebae. Only the polymorpho-nuclear leukocytes (PMN) apposed or topographically close to amebae exhibited degenerative changes which were characterized by condensation of nucleoplasm and cytoplasm, extra-cellular release of cytoplasmic components including granules, and, finally, lysis of cell membranes. Capillaries and venules in the lamina propria showed a variety of changes such as swelling and gap formation at the intercellular endothelial junctions and more rarely at the fenestrae. Blood vessels physically close to amebae showed formation of endothelial cytoplasmic blebs which pinched off into the vascular or extravascular space. Platelet and fibrin thromboses were common in the more severely damaged capillaries and venules. Fragments or clumps of fibrin-like material were found also in the extracellular spaces. Amebic invasion of the lamina propria, then, is accompanied by continued epithelial shedding, PMN degeneration, and changes in both capillaries and venules consisting of endothelial damage and occlusive thrombosis. The vascular changes appeared to be closely related to PMN degeneration resulting from interaction of PMN with invading amebae.

Amebiasis↗

Diarrhea: pathogenesis and diagnostic techniques.

Daily fecal weight is the feature most useful in defining diarrhea, as normal weights for various societies are known. Diarrhea is associated with increased fecal water excretion, with heightened sensitivity of the rectal mucosa, and with exudation of mucus. It occurs acutely, as in gastroenteritis, bacterial dysenteries, and parasitic infections, and chronically, as in functional disorders, malabsorption syndromes, and inflammatory bowel disease. Many seemingly unrelated diseases can also cause diarrhea. The patient's history as well as macroscopic, microscopic, and chemical analysis of stools will offer major clues to the cause of the ciarrhea.

Anti-Bacterial Agents↗

[Ambulant coloscopy in colitis ulcerosa and colorectal cancer].

In the first year after establishing a gastroenterological center in a vineyard and industrial district with 220.000 inhabitants we examined 1.171 patients. In 36.53% we had diseases in the lower gastrointestinal tract excluding proctological disturbances. We could find out 37 cases of colitis ulcerosa and 42 colorectal cancers. Excluding two cancers in colon transversum and ascendens all the tumors were found by coloscopy. Previously 4 cases of colitis ulcerosa were identified by other methods, clinically or by rectoscopy. In 48.6% of the colitis ulcerosa the transfer was done by reason of blood in the feces. The melaena lingers between 1 month and 10 years. Other presumed diagnoses for transfer to our Institute were gastroenteritis, proctitis, hemorrhoids, fissure or ileitis terminalis Crohn. In some rare cases the supposed diagnosis was salmonellosis or mycosis of the intestinum. In colorectal cancers the main reason for special gastroenterological investigation was the addition of blood to stool, whether microscopically or visible. Abdominal pain or ileus were following in frequency. Clinical symptoms were to be reconstructed in 30.9% for six weeks, in 59% for six months and in 9.5% up to one year. Most of the colorectal tumors (85.7%) were localized distal from splenic colonflexur, mostly in the rectosigmoid and colon descendens (see figure 1). Ambulant coloscopy is a method for quickly and definitive clarification, if the practitioner will refer swiftly.

Ambulatory Care↗