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Specific clonal T cell accumulation in intestinal lesions of Crohn's disease.

The initial cellular events that take place at the outset of autoimmune diseases and that may be the most important in terms of understanding their pathogenesis are poorly understood, especially in humans. This is mainly due to the difficulties in the identification of primary lesions and the accessibility to such material. In this respect, it is noteworthy that the appearance of small reddish erosions, known as aphthoid lesions, is known to be an early event in Crohn's disease. In the present study, accumulation of lesion-specific clonal TCR bands in the intestinal lesions of Crohn's disease patients was demonstrated by means of a highly sensitive method based on single strand conformational polymorphism. Such clonal accumulation was demonstrated in both aphthoid and discrete ulcer lesions. There were several TCR BV bands that were present in both aphthoid lesions and discrete ulcer lesions, but some were specific to the aphthoid lesions. In addition, the same aphthoid lesion-specific/dominant T cell clones were found to be expanded in separate aphthoid lesions of a single patient, and were absent from intervening, non-inflamed mucosa. Some of these bands may represent T cell clones activated primarily at the onset of disease.

Adolescent↗

Minute lesions of the rectum and sigmoid colon in patients with Crohn's disease.

Sigmoidoscopy with a spray of 0.1% indigocarmine was performed on 20 patients with Crohn's disease whose main lesions were located proximal to the transverse colon and on 10 age-matched healthy volunteers. Minute lesions such as apthoid lesions, areas of erythema, and small ulcers were found in 90% of patients with Crohn's disease and in 0% of healthy volunteers (p less than 0.001). Among the minute lesions, aphthoid lesions were found in the highest incidence (85%). It was difficult to determine the presence of aphthoid lesions without the spray of indigocarmine, which facilitated detection. Histologically, granulomas were found in 15% of patients with Crohn's disease. Aphthoid lesions were not associated with superficial erosions and lymphoid follicles. The presence of aphthoid lesions in the rectum and sigmoid colon would be a strong indication of the presence of Crohn's disease.

Adolescent↗

The effects of sodium phosphate and polyethylene glycol-electrolyte bowel preparation solutions on 2,4,6-trinitrobenzenesulfonic acid-induced colitis in the rat.

The aim of the present study is to evaluate the effects of sodium phosphate (NaP) and polyethylene glycol-electrolyte (PEG-EL) colon cleansing solutions on histopathology of 2,4,6-trinitrobenzene sulfonic acid (TNBS) and ethanol (E)-induced colitis in the rat and normal rat colon. The presence of hyperemia, inflammation and ulcer was evaluated to score of macroscopic morphologic damage. The microscopic criteria including ulceration, mucus cell depletion, crypt abscesses, inflammatory cysts, mucosal atrophy, edema, inflammatory cell infiltration, and vascular dilatation were evaluated to determine the extent of inflammatory reaction. Colitis findings were determined on the rats which were administered TNBS-E. Aphthoid lesions were seen 30% and 20 % of rats, respectively, by NaP and PEG-EL solutions in healthy group. Microscopic examination of aphthoid lesions revealed edema within the lamina propria and lymphoid hyperplasia in the mucosa and submucosa without erosion, ulceration and inflammatory cell infiltration. No significant difference was statistically found either macroscopically or microscopically in terms of the effects of saline, NaP and PEG-EL solutions in healthy rats and rats with colitis (p > .05). Under the present conditions, we concluded administration of NaP and PEG-EL solutions did not cause evident morphological changes on the rectal mucosa macroscopically and microscopically, although in a proportion of rats aphthoid lesions seem as a marker of mucosal damage macroscopically.

Animals↗

Early lesions of Crohn's disease.

In its early stages, Crohn's disease may be manifested as small aphthoid ulcers. Because these ulcers are small and shallow, they are difficult or impossible to demonstrate on conventional barium-filled studies of the gastrointestinal tract. Using double contrast techniques, we have been able to demonstrate these early lesions of Crohn's disease in the colon, small bowel, and stomach. The aphthoid ulcers produce a "bulls-eye" or "target" lesion consisting of a small central collection of barium surrounded by radiolucent halo due to the granulomatous inflammation. The appearance is identical in the colon, small bowel, and stomach. The early lesions may be seen adjacent to or at a distance from a segment of more severe disease. In some patients, only these early lesions are found. The radiologic demonstration of these aphthoid ulcers allows for early diagnosis, facilitates differentiation between ulcerative and granulomatous collitis, and is important for planning appropriate therapy.

Colonic Diseases↗

The value of double-contrast barium enema in amebic colitis.

We report here our findings on the double-contrast barium enema given to 8 patients with amebic colitis and a comparison is made with endoscopic features. A definite diagnosis of amebic colitis was made by fecal examination or by endoscopic biopsy. Radiologic findings included fine marginal serration, aphthoid ulcers, minute barium flecks, marginal defects, loss of haustration, and deformities of the bowel. Aphthoid ulcers and marginal defects are both characteristic of amebic colitis. The double-contrast barium enema is most useful for differentiating amebiasis from other forms of colitis.

Adult↗

Roentgenologic changes of the colon in Campylobacter infection.

A double-contrast examination of the colon was performed during diarrheal illness in 5 patients with Campylobacter infection. The findings in these 5 patients were aphthoid ulcers and stippled appearance. In 1 patient with stool culture positive for Campylobacter, double-contrast study of the colon 9 days later showed no abnormalities. In a 12-year-old boy lymphoid hyperplasia could be observed as well as the aphthoid ulcers. All the abnormalities were segmental, more often localized in the rectosigmoid. No changes were found in the ascending colon. Histopathologic studies of the biopsy specimens taken endoscopically in 3 patients showed a nonspecific inflammatory reaction.

Adult↗

[Aphthae and aphthous lesions of the mouth mucosa].

Recurrent aphthae (or aphthoses) are the most frequent inflammatory lesions of the oral mucosa. Aphthae can clearly be defined, but may also be barely discernible from aphthoid erosions and ulcers of heterogeneous origin. Although a subject of molecular research, the etiopathogenesis of oral aphthoses is still unknown. However, the clinical differentiation of a "benign" type of aphthosis from a "pernicious" one, such as Behçet's disease (BD), is a diagnostic matter of great significance. BD has been found clinically in increasing numbers in central Europe and represents an (auto-)hyperimmune multisystem life-threatening vasculitis. In this disorder possible damage can occur to many visceral organs and/or the cerebrospinal system. The prognosis of BD may depend on the changing involvement of very different organs, as well as the early recognition of the disease per se. The most prominent feature is a multilesional aphthous stomatitis that is almost never absent during acute episodes of BD. Hence, the occurrence of this peculiar type of aphthosis strongly indicates an active BD. The plethora of other aphthoid lesions can be challenging to the diagnostic competence of all physicians and may confuse the correct recognition of the severity of the disease present. This review particularly details the wide range of diagnostic, therapeutic and prognostic aspects of the various oral aphthoses.

Behcet Syndrome↗

Primary colorectal T-cell lymphoma.

We report here a case of primary colorectal T-cell lymphoma in a 49-year-old man. Eighteen years previously, he was diagnosed as having ulcerative colitis based on the findings of colonoscopy and a barium enema. Since then, he had been treated with salicylazosulfapyridine until the most recent episode. He was refered to our clinic with the chief complaint of abdominal pain and excretion of mucus, and for a workup of bowel lesions. Physical examination results were not remarkable, except for the presence of low-grade fever. Total colonoscopy showed multiple shallow ulcers and aphthoid erosions through the entire colon and rectum, except for the descending colon. Endoscopic findings of the descending colon were normal, which was different from the findings of the active stage of ulcerative colitis. Biopsy specimens from the colon and rectum with ulcerations and aphthoid erosions showed a diffuse proliferation of medium-sized to large atypical lymphoid cells with irregular and indistinct nucleoli, thus revealing malignant lymphoma, diffuse pleomorphic type. The lymphoma cells were positive for CD2, CD3, CD5, CD8, and T-cell receptor (TCR) beta F1, but negative for CD4, CD19, CD20, CD103, and CD56. Southern blotting revealed rearrangement of TCR. Based on these findings, the patient was diagnosed as having high-grade T-cell lymphoma. The findings of computerized tomography of the chest and abdomen, gallium scintigraphy, and abdominal ultrasonography were all normal. There were no abdominal lesions throughout the esophagus, stomach, duodenum, and small intestine. As the patient refused total proctocolectomy, he was treated with one course of CHOP (cyclophosphamide, vincristine, adriamycin, and prednisolone) and subsequently with three courses of ProMACE-CytaBOM (consisting of cyclophosphamide, adriamycin, etoposide, cytarabine, bleomycin, vincristine, methotrexate, and prednisolone). After the therapy, improvement of the colorectal lesions was observed, though lesions clearly still remained. To our knowledge, this is the first case report of primary colorectal T-cell lymphoma with cytotoxic/suppressor T-cell phenotype.

Antineoplastic Combined Chemotherapy Protocols↗

Colonic mucosal abnormalities associated with oral sodium phosphate solution.

BACKGROUND: Oral sodium phosphate (NaP) is increasingly used as a colonic cleansing agent for colonoscopy. It has been shown to be efficacious, well-tolerated, and safe. Mucosal abnormalities associated with NaP have recently been described. We carried out this controlled study to assess whether bowel cleansing preparations commonly used in colonoscopy are associated with colonic mucosal changes that may mimic inflammatory bowel disease (IBD). METHOD: All patients undergoing colonoscopy from January 1994 to June 1994 were considered for the study. Patients with history or symptoms suggestive of IBD were excluded. Patients were randomized to receive polyethylene glycol-based lavage (PEG-ELS) or NaP solution as their bowel cleansing preparation. Two gastroenterologists performing the colonoscopies were blinded to the type of preparation. Any mucosal abnormalities were noted and photographic documentation and biopsy specimens were taken. RESULTS: Ninety-seven patients were studied, 44 receiving PEG-ELS and 53 receiving NaP. Both groups were similar with regard to sex, age, and indication for colonoscopy. Fourteen patients were found to have nonspecific aphthoid-like erosions similar in appearance to Crohn's disease. These lesions, however, were not friable and biopsy results were not compatible with IBD. This mucosal abnormality was found in 13 patients who received NaP (24.5%) and only 1 patient who received PEG-ELS (2.3%). CONCLUSION: Nonspecific aphthoid-like mucosal lesions occur frequently in patients who received NaP for colonoscopy preparation. These lesions are endoscopically similar to those seen in Crohn's disease. Because of the potential for misinterpretation of these lesions, we do not recommend the use of NaP as a colonic cleansing preparation for patients with chronic diarrhea or in whom the diagnosis of IBD is suspected.

Administration, Oral↗

Cytomegalovirus enterocolitis in an immunocompetent individual.

We report a rare case of cytomegalovirus (CMV) enterocolitis in a healthy 57-year-old woman. In March 1999, she developed hematochezia, diarrhea, and abdominal pain. Total colonoscopy on March 17th showed multiple aphthoid lesions and friable mucosa from the terminal ileum to the rectum and a shallow ulcer on the ileocecal valve. Repeat total colonoscopy on April 19th showed faded aphthoid lesions in the terminal ileum, and biopsy specimen revealed CMV inclusion bodies. Symptoms and endoscopic findings improved without any specific medication. In previous reports, the definition of "immunocompetent individual" varied. Here, we define immunocompetent individual as one who has no associated diseases, is not under immunosuppressive therapy, has no recent history of operation, is negative for human immunodeficiency virus antibody, is not pregnant, has no obvious infectious course, and is less than 70 years of age. This is the ninth report of CMV enterocolitis in an immunocompetent individual in the world literature.

Colonoscopy↗

Endoscopic diagnosis of lower intestinal lesions of leukaemia and malignant lymphoma.

There have been only a few endoscopic studies with respect to lower intestinal lesions of leukaemia and malignant lymphoma, although there have been many autopsy studies of these lesions. The aim of this study was to clarify these lesions using endoscopy. Colonoscopy was performed on 11 of 341 patients with leukaemia and on 32 of 105 patients with malignant lymphoma for frequent diarrhoea, anal bleeding or abnormal findings on barium enema examination, between April 1984 and September 1994. In eight of the 11 patients with leukaemia on whom endoscopy was performed, nine lesions were found; aphthoid ulcers, small ulcers or large tumours due to leukaemic infiltration were found in five, and colorectal adenoma was found in only one patient. Antibiotic-associated haemorrhagic colitis or pseudomembranous colitis was found in one patient each. In 10 of the 32 patients with malignant lymphoma, 11 lesions were found. The following were found in one patient each: large lymphomatous tumours, a large lymphomatous ulcer, multiple small polypoid lesions, multiple lymphomatous polyposis; and colorectal cancer or adenoma in six patients. However, the autopsy findings in patients with both diseases were mostly pseudomembrane formation or ulcers due to fungal and/or bacterial infection. It is concluded that accurate endoscopic diagnosis of lower intestinal lesions in patients with leukaemia or malignant lymphoma is essential for staging and treatment of these diseases and for determining their prognosis. Most lesions in leukaemia are aphthoid and small ulcers are due to leukaemic infiltration or antibiotics; most lesions in malignant lymphoma are elevated lesions such as cancer, adenoma or lymphomatous lesions as determined by endoscopy. This is in contrast to pseudomembrane formation or ulcers due to fungal and/or bacterial infection which are detected at autopsy.

Adult↗

Metastasising malignant lymphoma mimicking necrotising and hyperplastic gingivostomatitis.

This paper presents the case of a 65 year-old woman suffering from recurrent oral aphthoid ulcers which rapidly evolved towards hyperplastic and ulcerated lesions over the entire floor of the mouth. The initial lesions were interpreted as non-specific aphthoid ulcers. Later, a tentative diagnosis of necrotising stomatitis with secondary reactive proliferating epithelial hyperplasia was made. The clinical symptoms and the immuno-phenotyping of lymphocytes circulating in the peripheral blood suggested the diagnosis of CD30-positive large cell anaplastic lymphoma. The biopsy showed only a pseudoepitheliomatous hyperplasia, reactive infiltrates and no lymphoma cells. The disease ran a fulminant course leading to death within 4 weeks due to acute gastro-intestinal bleeding. Autopsy revealed infiltrates of CD30+ large cell anaplastic lymphoma in a submandibular lymph node, in a thrombus stenosing the right subclavian vein, in the spleen, the anterior and posterior gastric wall as well as in the depth of the tumour on the floor of the mouth. The clinical and histopathological spectrum of CD30+ large cell anaplastic lymphoma is considerably variable. The particular feature of pseudoepitheliomatous hyperplasia has been reported especially in CD30+ anaplastic large cell lymphomas. An early correct diagnosis is rendered difficult in insufficient biopsy size, becauses this type of lymphoma often simulates other inflammatory or neoplastic skin diseases. Thus, with a necrotising and hyperplastic gingivostomatitis, the diagnosis of a CD30+ anaplastic large cell lymphoma should be considered.

Aged↗

[Two cases of rheumatoid arthritis complicated with vasculitis-induced ischemic enterocolitis].

Episodes of catastrophic entero-colitis associated with mesenteric vascular insufficiency in patients with rheumatoid arthritis(RA) have rarely been recorded thus far. We herein report two cases of RA complicated with severe attacks of entero-colitis presumably due to mesenteric vasculitis. Surgical intervention was necessary in the first case, while the second patient recovered well only through conservative therapy. Case 1: A 74-year-old man with history of RA since 1985 started to complain of abdominal discomfort and nausea early in February, 1989. On February 12, Episodes of tarry stool developed. Rapid down-hill clinical course prompted laparotomy under the clinical diagnosis of peritonitis. Ischemic changes were observed at the ileum end, the entire length of which was 120 cm orally from the cecum. The site was resected. Multiple linear and aphthoid ulcer lesions were discovered throughout the entire lumen. Histopathologically, evidence of necrotizing vasculitis such as fibrinoid necrosis and mural thrombi was demonstrated in small arteries of the submucosal layer underlying the ulcer lesion. Case 2: A 63-year-old woman who had been suffering from RA since 1980 noticed the onset of nausea, abdominal pain and bloody diarrhea in July, 1989. Colonoscopy examination revealed multiple linear and aphthoid ulcers in the sigmoid colon which was presumed to be due to ischemia. Laboratory evaluation at that time demonstrated hypocomplementemia, positive circulating immune complex and high titer of anti-DNA antibody. Corticosteroid therapy with moderate dose was successful in alleviation of all the abnormal findings and the patient fully recovered three months after her initial GI episode.

Aged↗

Ultrastructural pathology of Crohn's disease: correlated transmission electron microscopy, scanning electron microscopy, and freeze fracture studies.

The mucosa of the ileum or colon from 16 patients with active Crohn's disease was studied using transmission electron microscopy of thin sections, scanning electron microscopy, and freeze fracture electron microscopy. Electron micrographs of diseased tissue, as well as of grossly normal resection margins, were studied. Correlations of mucosal disease, as seen with the various ultrastructural techniques, were made and compared to controls. Alterations of epithelial cell tight junctions in freeze fracture replicas correlated with a decrease in the number of pinpoint contacts between adjacent cells in transmission electron microscopy preparations. Gap junctions in Crohn's disease did not vary with respect to structure or number, when compared to controls. Mucosal microulcerations, affecting 1 to 6 cells, were observed in transmission and scanning electron microscopy preparations. Possible freeze fracture electron microscopy correlates of microulcers consisted of replicas of cells completely devoid of tight junctional structures. "Aphthoid" type ulcers were studied with the various ultrastructural tools and were remarkable for several abnormalities of villi bordering the aphthoid ulcers, as well as surrounding villi. Transmission, scanning, and freeze fracture electron microscopy each provide unique and confirming data that may be used to construct a model for the pathophysiology of Crohn's disease.

Colitis↗

The "early" ulcerative lesion of Crohn's disease: correlative light- and scanning electron-microscopic studies.

Submucosal edema and lymphectasia have traditionally been considered the earliest recognizable alterations in Crohn's disease. However, a characteristic pattern of ulceration grossly resembling the oral lesions of aphthous stomatitis is believed by others to be the earliest macroscopic lesion. We have studied 50 consecutively accessioned surgical specimens with Crohn's disease in an effort to define more thoroughly the frequency, distribution, and morphology of these "aphthoid" ulcers. The scanning electron microscope (SEM) was used in the study because an understanding of the morphology and evolution of these lesions requires an appreciation of their three-dimensional configuration. Typical "aphthoid" ulcers were identified in 35 of the 50 specimens studied. Grossly the typical ulcerative lesion varies from barely visible up to 3 mm in diameter. They have a characteristic light-microscopic appearance consisting of focal ulceration usually overlying an aggregate of lymphoid tissue. The SEM was helpful in identifying the smallest of these lesions and was especially useful in defining a variety of villous abnormalities in the small bowel mucosa adjacent to the ulcers.

Adolescent↗

Idiopathic inflammatory bowel diseases: immunological hypothesis.

Circumstantial evidence indicates that immunological mechanisms are important in the pathogenesis of inflammatory bowel diseases. In Crohn's disease lesions the naive T cells are reduced and memory T cells are increased in number. Colonocytes of normal mucosa do not express MHC class II molecules but aberrant HLA-DR expression is induced in inflammatory conditions. Also in ileal epithelial cells there is increased MHC class II molecules expression suggesting augmented antigen presentation. Once the initiating event (environmental, dietary, infectious or enterobacterial products) has activated inflammatory cells, an auto-amplifying inflammatory immune cascade is induced by numerous agents such as cytokines, transforming growth factors, leukotrienes, prostaglandins and other mediators. Tissue injury may be caused by oxygen free radicals generated by neutrophils and macrophages. The inflammatory process can be perpetuated by a persistent antigenic stimulus or alternatively, by abnormal regulation of immune and inflammatory responses. This can mean exaggerated activation of inflammatory responses to "normal" stimuli or defective feedback mechanisms of down-regulation. The early lesions of inflammatory bowel disease are patchy necrosis of the surface epithelium, focal accumulations of leukocytes adjacent to crypts and an increased number of intraepithelial lymphocytes. In Crohn's disease the earliest lesions are aphthoid ulcers overlying lymphoid follicles in the terminal ileum. In patients with spondylarthropathy and asymptomatic intestinal inflammation we demonstrated lesions in the top of the follicle associated epithelium. The changes consist of increase in number of membranous (M) epithelial cells, ruptures, fissures and perforations of M cells. Aphthoid ulcers that may occur in the entire gastrointestinal tract are typically found at the M cell level.(ABSTRACT TRUNCATED AT 250 WORDS)

Colitis, Ulcerative↗

Gastrointestinal milk intolerance of infancy.

During a period of 30 months, cow's milk- or soy protein-induced colitis was diagnosed in 22 infants. All patients presented with hematochezia. Only three patients had substantial diarrhea. Colonoscopic evaluations demonstrated a characteristic mucosal appearance, manifested by aphthoid ulcerations with intervening, normal-appearing mucosa. Histologic findings included surface ulcerations and associated inflammation of the lamina propria and submucosa, marked by substantial eosinophilic infiltration. Both clinical symptoms and colonoscopic abnormalities rapidly resolved in all patients after the elimination of cow's milk and/or soy protein from the diet. These data indicate that hematochezia may be the predominant symptom of cow's milk protein and soy protein intolerance in many affected infants, and that colonoscopy is the most effective means of establishing a definitive diagnosis in this patient population.

Colitis↗

The postoperative recurrence of Crohn's disease: an analysis of 37 patients with Crohn's disease who underwent endoscopy during initial surgery.

A total 37 patients with Crohn's disease who underwent intraoperative endoscopy during resection of the affected intestine were evaluated in this study. The average age of the patients at surgery was 23.2 years. The residual lesions in the remaining intestine identified by intraoperative endoscopy were classified according to their pathologic profiles into three groups: A, B and C. In group A, comprising patients with longitudinal ulcers and/or a cobblestone appearance, 10 of 12 patients had recurrence. In 5 of these 10, the residual lesions were exacerbated and 2 required a further operation. The remaining 5 patients showed recurrence at the site of previous anastomosis and 2 of these 5 required additional surgery. In group B, comprising patients with small ulcers, aphthoid ulcers, or scars, and group C, comprising patients with no residual lesions, recurrence was observed in 13 of 16, and 3 of 9 patients, respectively. The recurrent lesions were all found proximal to, or at the site of previous anastomosis. Additional operations were performed on 3 of the group B patients. The findings of this study revealed that recurrence requiring additional surgery is more frequent at the site of anastomosis, regardless of the endoscopic appearance of the residual lesions.

Adolescent↗