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Cerebral thrombosis and vasculitis: an uncommon complication of ulcerative colitis.

Cerebral thrombotic disease is a rare and nearly always fatal complication of ulcerative colitis. It is associated with a necrotizing vasculitis. We report a fatal case with a confusing neurologic picture arising from this complication. Autopsy revealed necrosis and hemorrhages affecting both cortical grey and white matter. Microscopic examination showed thrombosis of small and medium size vessels associated with hemorrhages and a necrotizing angiitis. Ulcerations, hemorrhages, pseudopolyps, and cryptic abscesses were found in the rectosigmoid region of the colon compatible with active ulcerative colitis. A sudden neurologic deficit in a patient with ulcerative colitis should direct attention to the consideration of a cerebral thrombotic event and the possibility of an associated cerebral vasculitis. Diagnosis may be strongly suggested by MRI or arteriography, but it may require confirmation by biopsy of the brain parenchyma and leptomeninges. A hypercoagulable state has been associated with the thrombosis. Anticoagulation has yielded successful results in some patients with cerebral thrombosis but the risk of massive intracranial and gastrointestinal bleeding preclude to establish clear indications. Neurologic improvement has been obtained with the use of steroids and cyclophosphamide.

Autopsy↗

Ischemic colitis.

Twenty cases of ischemic colitis are reviewed; 19 were obtained from autopsy files and the diagnosis in one was made from a surgical specimen. The majority of the patients were elderly with generalized arteriosclerosis. In approximately two-thirds of the patients the ischemic colitis was precipitated by preceding trauma, operation or congestive heart failure. Clinically, ischemic colitis is characterized by abdominal pain, distension and bleeding per rectum. Perforation of large bowel may occur. The lesions tend to be localized around the splenic flexure and junction of the descending and sigmoid colon, and in cases following aortic graft surgery the rectum is involved. Microscopically, there is necrosis, hemorrhage and ulceration. In less severe cases the mucosa only is affected. Cases with perforation show necrosis of all layers. It is considered that ischemic colitis is comparatively frequent and should be distinguished from other inflammatory conditions of the colon.

Aged↗

[Inflammatory bowel disease in childhood].

Inflammatory bowel disease in childhood is becoming increasingly important as a result of a marked increase in incidence occurring over the past 20 years. In Crohn's disease the onset is commonly insidious, with symptoms such as growth failure, which do not immediately suggest intestinal disease. This may result in a correct diagnosis being delayed for several years. The role of paediatric colonoscopy is discussed, together with the macroscopic and microscopic appearances of the lesions. The indications and efficacy of drug therapy in Crohn's disease and ulcerative colitis are outlined and the importance of nutritional support, particularly in children with growth failure, is discussed. The indications for surgery are summarised and the need for a multidisciplinary approach, particularly in cases of fulminating colitis where early surgery is indicated, is emphasised. Most children with inflammatory bowel disease do reasonably well and even those children undergoing proctocolectomy adapt to a stoma provided they receive optimal psycho-social preparation and support.

Child↗

Metastatic protothecal retinitis in a dog. Electron microscopic observations.

Disseminated protothecosis, due to Prototheca wickerhamii, was present in a two-year-old female dog with a nine-month history of hemorrhagic colitis and diarrhea. Shortly thereafter, the dog developed "acute blindness" of the left eye. Euthanasia was done after medical therapy failed to control the disease. Histologically, the eye had multiple microabscesses and necrotic foci containing myriad protothecal organisms under the detached retina. Numerous organisms also were present in the mucosa and walls of the colon. The identification of P. wickerhamii was confirmed by the histologic appearance and immunofluorescent studies. The ultrastructural features of P. wickerhamii also were studied.

Animals↗

[Collagen colitis: separate illness or syndrome?].

Six patients with collagenous colitis are described and the literature is reviewed. Collagenous colitis is not a rare disease. Its most prominent feature is profuse watery diarrhoea. Although the endoscopic picture of the mucosa is usually normal, there is a microscopic thickening of the (subepithelial) basement membrane. For diagnostic purposes, multiple colon biopsies are warranted in patients with chronic or relapsing diarrhoea. There is no established therapy for this disease.

Adult↗

Epidermolysis bullosa acquisita and Crohn's disease. A case report with immunological and electron microscopic studies.

A review of the literature shows that the association of epidermolysis bullosa acquisita and Crohn's disease is rare. A 27-year-old man developed cutaneous blisters on the trauma-prone areas that were consistent with the diagnosis of epidermolysis bullosa acquisita. Immunological and electron-microscopic studies of the skin showed intense IgG deposits located beneath the basal lamina. Three years later, Crohn's colitis was diagnosed. Prednisolone and sulfasalazine treatment resulted in an improvement of the bowel disease but without appreciable effect on the skin lesions.

Adult↗

Is nitric oxide and heparin treatment justified in inflammatory bowel disease? An experimental study.

Microcirculatory disturbances of the colon may contribute to the pathogenesis of inflammatory bowel disease. The aim of the study was to investigate the alterations of rectal blood perfusion in experimental colitis with reference to nitric oxide and heparin treatment. The study was carried out on 36 rats, divided into six groups: group I, control; group II, control + NG-nitro-L-arginine (L-NNA); group III, colitis without treatment; group IV, colitis + L-arginine; group V, colitis + L-NNA; group VI, colitis + heparin treatment. Experimental colitis was induced by 4% acetic acid enema, and 48 h after the enema, besides the measurement of rectal capillary blood flow by means of laser Doppler flowmetry, the serum interleukin-6 (IL-6) level and histopathological alterations within the rectal mucosa were examined. Experimental colitis resulted in a drop in rectal wall perfusion. L-Arginine and heparin treatment improved the microcirculatory values. The highest IL-6 level and the most advanced histopathological alterations were observed in the rats treated with L-NNA. L-Arginine treatment had no influence on IL-6 concentration, however it aggravated the inflammatory changes within the rectal mucosa. Heparin administration reduced the IL-6 values and also had a positive impact on the microscopic alterations within the rectal wall. It is concluded that heparin treatment has a beneficial effect on the microcirculatory disturbances and inflammatory changes observed in experimental colitis. The inhibition of nitric oxide-synthase aggravated the course of experimental colitis. L-Arginine administration improves the rectal blood flow but aggravates the histopathological alterations within the rectal wall.

Acetic Acid↗

Equine colitis "X", still an enigma?

Colitis "X" is a sporadic diarrheal disease of horses with clinical signs of dehydration, electrolyte imbalances and "shock"-like features. Macroscopic and microscopic findings include signs of disseminated intravascular coagulation, necrosis of colonic mucosa and presence of large numbers of bacteria in the devitalized parts of the intestine. Recently published work suggests that the causative agent may be Clostridium perfringens, Type A, but the bacteria are recoverable only in the preliminary stages of the disease. Excess protein and lack of cellulose content in the diet is thought to be the trigger for the multiplication of the clostridial organisms. The pathological findings are pathognomonic, but clinically, a number of differential diagnoses have to be considered, such as intestinal accidents, salmonellosis, heavy metal intoxication and occlusive verminous arteritis.

Animals↗

Pathological changes in the rabbit ileal loop model caused by Campylobacter jejuni from human colitis.

Four strains of Campylobacter jejuni isolated from children with inflammatory diarrhoea were assayed in the rabbit ileal loop model of infectious diarrhoea. All caused inflammatory reactions with severe macroscopic and microscopic damage in infected rabbit ileal tissue similar to that observed in the patients by endoscopy and histological analysis of colonic biopsies. Haemoglobin and other proteins were observed in loop fluids, consistent with leakage of serum from damaged mucosa. Loop fluids also contained significant bicarbonate concentrations, indicative of an active secretory component similar to that in control loops inoculated with cholera toxin. However, although three of the four clinical strains produced small amounts of a protein immunologically related to cholera toxin in vitro, none such was detected in either tissues or fluids of infected ileal loops. We propose instead that host-derived mediators of secretion may be important in pathogenesis. A mutant strain of C. jejuni with impaired motility, obtained from the National Collection of Type Cultures, did not induce tissue damage or fluid secretion in rabbit ileal loops.

Animals↗

[Secondary membranous glomerulonephritis].

Following 689 percutaneous renal biopsies, membranous glomerulonephritis was proved in 68 patients. In 16 (23.5%) an underlying primary disease was verified, and thus the glomerulonephritis the secondary form. The primary disease was SLE in 5 cases, diabetes mellitus in 5 cases, rheumatoid arthritis in 3 cases, chronic active hepatitis in 2 cases, an ulcerative colitis and eosinophilic angiolymphoid hyperplasia in 1 patient. As initial sign, nephrotic syndrome emerged in 87.5% of the 16 cases. Microscopic haematuria was observed in half of the patients, as was hypertension, while acute renal failure presented in only 1 case. Histologically, in 13 cases the predominance of early glomerular alterations was characteristic, while in 9 cases the picture proved to be equivocal and accompanied by some degree of interstitial alterations. During combined treatment, remission was achieved in 75%. Two patients with SLE died, but not as a consequence of renal failure. Transient side-effects of the treatment were registered in 5 cases. The principal pathogenetic and clinical differences between the individual secondary nephritis forms, and the difficulty of their differentiation from the idiopathic cases, even on repeated examination, are emphasized. In 3 patients the possibility of secondary renal processes was suggested by the histological picture, and this was proved by the detailed clinical findings.

Adult↗

Therapeutic effects of an oral adsorbent on acute dextran sulphate sodium-induced colitis and its recovery phase in rats, especially effects of elimination of bile acids in gut lumen.

BACKGROUND: The pathogenesis of inflammatory bowel disease is still unknown. However, it is possible that faecal bile acids influence the clinical course. AIMS: To evaluate the eliminating effects of faecal bile acids by the oral adsorbent on dextran sulphate sodium-induced rat colitis. METHODS: Rats were given 3% dextran sulphate sodium aqueous solution for 7 days, with or without concomitant administration of oral adsorbent, or the rats were given dextran sulphate sodium for 7 days, followed with or without oral adsorbent for 5 days. Macroscopic and microscopic examinations of the colons and measurement of faecal bile acids were performed. The cytotoxicity of bile salts on Caco-2 cells was also evaluated. RESULTS: Oral adsorbent tended to attenuate the dextran sulphate sodium-induced colitis. Oral adsorbent was fairly effective in reducing faecal hyodeoxycholic acid concentration. A positive correlation was found between the size of the ulcer area and the faecal hyodeoxycholic acid concentration. In a cell culture study, cytotoxicity of bile acid was parallel with increasing hydrophobicity of the bile acid. However, hyodeoxycholate exhibited severe cytotoxicity, despite its hydrophilic properties. CONCLUSIONS: Oral adsorbent tended to attenuate the dextran sulphate sodium-induced colitis and tended to promote the recovery process. It is possible that bile acids in the gut lumen influence the progression of dextran sulphate sodium-induced colitis and its repair process.

Acute Disease↗

Phlebosclerotic colitis coincident with carcinoma in adenoma.

Phlebosclerosis of the colon is a rare disease characterized by a thickening of the wall of the colon with fibrosis, hyalinization and calcification to the affected veins. These symptoms result in a type of ischemic colitis known as phlebosclerotic colitis. A case of phlebosclerotic colitis coincident with carcinoma in adenoma is reported. A 74-year-old Japanese woman was admitted to hospital because of a mass in her right lower abdomen. Abdominal computed tomography examination revealed linear calcifications in the wall of the cecum and the ascending colon. Colonoscopy revealed dark purple mucosa with multiple ulcers in the cecum and the ascending colon. Biopsy specimens showed a marked hyalinous thickening of the wall of small blood vessels in the mucosa. Phlebosclerotic colitis was suspected because of negative results with amyloid stain. Alternative ileocolic angiography showed the serpentine of the peripheral nature blood vessels and pooling at the late venous phase. Microscopic examination of the surgically resected colon revealed mucosal and submucosal fibrosis, and a thickening of the venous wall with fibrosis, hyalinization and calcification from the mucosa to the serosa, which caused a marked luminal narrowing. A small polypoid lesion was also found in the affected region and was diagnosed histologically as carcinoma in adenoma. To our knowledge, this is the first reported case of phlebosclerotic colitis complicated by carcinoma.

Adenoma↗

Prophylactic effect of dietary glutamine supplementation on interleukin 8 and tumour necrosis factor alpha production in trinitrobenzene sulphonic acid induced colitis.

BACKGROUND: It is well established that glutamine supplemented elemental diets result in less severe intestinal damage in experimental colitis. However, few studies have examined the mode of action of glutamine in reducing intestinal damage. AIMS: To examine the effects of glutamine supplemented elemental diets on the potent inflammatory cytokines interleukin 8 (IL-8) and tumour necrosis factor alpha (TNF-alpha) in trinitrobenzene sulphonic acid (TNBS) induced colitis which presents with both acute and chronic features of ulcerative colitis. METHODS: Sprague-Dawley rats were randomised into three dietary groups and fed 20% casein (controls), or 20% casein supplemented with either 2% glutamine (2% Gln) or 4% glutamine (4% Gln). After two weeks they received intracolonic TNBS to induce colitis. RESULTS: Both Gln groups of rats gained more weight than the control group (p < 0.05) which had progressive weight loss. Colon weight, macroscopic, and microscopic damage scores for the Gln groups were lower than in the control group (p < 0.05). IL-8 and TNF-alpha concentrations in inflamed colonic tissues were lower in the Gln groups than in the control group (p < 0.05), and correlated well with disease severity. Bacterial translocation was lower both in incidence (p < 0.05) and in the number of colony forming units (p < 0.05) for the Gln groups, than in the control group. With respect to all indices studied, the 4% Gln group performed better than did the 2% Gln group. CONCLUSION: Prophylactic glutamine supplementation modulates the inflammatory activities of IL-8 and TNF-alpha in TNBS induced colitis.

Analysis of Variance↗

Effect of growth hormone on the inflammatory activity of experimental colitis in rats.

The effect of daily treatment with 2.0 mg biosynthetic human growth hormone per kilogram body weight or isotonic NaCl (controls) on experimental colitis was investigated in rats. Colonic inflammation was induced by instillation of trinitrobenzene sulfonic acid (TNB) intraluminally into the left colon. Untreated NaCl-instilled rats were used for comparison with intact colon. Four days after TNB instillation the growth hormone-treated rats had lower macroscopic and microscopic damage scores and less infiltration of neutrophils, measured as myeloperoxidase activity (MPO), than controls. The biomechanical properties of the colon showed that the breaking strength and energy absorption were reduced in the control rats with colitis compared with intact colon, whereas the rats treated with growth hormone had unchanged strength and energy absorption. The differences in MPO activity, damage scores, and biomechanical properties were associated with a higher concentration of insulin-like growth factor I in serum from growth hormone-treated rats after 4 days than controls. Finally, the growth hormone-treated rats regained their initial body weight after 7 days, in contrast to the body weight of control rats, which remained 11% lower than their initial body weight.

Animals↗

Acute ischaemic colitis following intravenous cocaine use.

Intestinal ischaemia is an uncommon complication of recreational cocaine abuse. We report the case of a 36-year-old male who underwent emergency surgery for acute abdomen. At laparotomy, the transverse colon appeared markedly oedematous, dilated and with subserosal haemorrhage. Segmental resection was performed and microscopic examination of the resected specimen showed focal necrosis of the mucosa with a patchy polymorphonuclear and mononuclear infiltrate. The submucosa was markedly thickened due to oedema; focal haemorrhage was observed and blood vessels were dilated but showed no structural abnormalities or thrombosis. These findings were consistent with ischaemic colitis. No risk factors for intestinal ischaemia were present but the patient stated that he had injected cocaine i.v. the day before the onset of symptoms. He was not a cocaine abuser but occasionally sniffed, smoked or injected cocaine. Cocaine use should be considered in the aetiological diagnosis of intestinal ischaemia in young patients.

Adult↗

Therapeutic role for bismuth compounds in TNBS-induced colitis in the rat.

The 2,4,6-trinitrobenzene sulfonic acid (TNBS) -induced model of chronic inflammation of the rat colon was used to determine the efficacy of bismuth subsalicylate (BSS), bismuth subcitrate (CBS), and 5-aminosalicylic acid (5-ASA) administered in enema form. A novel bismuth compound 1, 2-bis[2-(1,3-dithiobismolane)thio]ethane [Bi2(EDT)3] was also tested. On day 1 colitis was induced with 50 mg TNBS/50% ethanol in female Sprague-Dawley rats, while controls received a saline enema. On day 3, twice-daily treatment with enemas of either saline, BSS, CBS, Bi2(EDT)3, or 5-ASA were initiated in the colitis and control rats. All rats were killed on day 14, and the colons excised, weighed, rated macroscopically, and then fixed for hematoxylin and eosin staining. Blinded microscopic scoring was used to determine injury and healing in all groups. Colon mass and macroscopic scores were increased (P < 0.05) in the group of rats treated with TNBS (N = 16) compared to saline controls (N = 12). Colon mass and macroscopic scores in controls treated with BSS (N = 4), CBS (N = 4), Bi2(EDT)3 (N = 4), and 5-ASA (N = 4) alone did not differ from saline control animals. Macroscopic scoring showed a decrease (P < 0.05) in the degree of damage in the group of rats treated with TNBS plus BSS (N = 15), TNBS plus Bi2(EDT)3 (N = 10) and TNBS plus CBS (N = 4) compared to the group of rats treated with TNBS plus saline (N = 16). A decrease (P < 0.05) in injury and an increase (P < 0.05, Kruskal-Wallis) in healing was observed in the groups of rats treated with TNBS plus BSS, TNBS plus CBS, and TNBS plus 5-ASA compared to the group of rats treated with TNBS plus saline. It appeared that Bi2(EDT)3 was not protective against injury at the microscopic level but that the novel Bi2(EDT)3 has an effective healing capacity at the macroscopic level. We conclude that BSS and CBS decrease injury and/or promote healing as effectively as 5-ASA in this model.

Animals↗