Abnormal lymphatics and sarcoidosis.
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Granuloma↗
Biomedical subjects
C Cuvelier
Publications and source records attributed to C Cuvelier.
T cell receptor V beta usage in rheumatoid nodules: marked oligoclonality among IL-2 expanded lymphocytes.
Rheumatoid arthritis is an autoimmune disease which is characterized by chronic polyarthritis and joint destruction as well as by extra-articular manifestations, typically including the appearance of rheumatoid nodules. Although the pathogenesis of the disease is unknown, substantial evidence suggests that it is T cell-mediated. In contrast to experimental models, the disease-mediating T cells in the human situation have never been isolated or identified. We expanded T lymphocytes from human rheumatoid nodules by IL-2 stimulation and observed a marked oligoclonality among these expanded lymphocytes. This tendency towards oligoclonality was not seen in IL-2-expanded lymphocytes from peripheral blood. We hypothesize that this oligoclonal expansion reflects a clonally restricted in situ preactivation of lymphocytes and that precisely these preactivated cells are involved in the pathogenesis of the rheumatic process.
Aged↗
Gut inflammation in children with late onset pauciarticular juvenile chronic arthritis and evolution to adult spondyloarthropathy--a prospective study.
Ileocolonoscopy with biopsy of the colon and terminal ileum was performed prospectively on 12 patients under age 16 with late onset juvenile chronic arthritis (JCA). Inflammatory gut lesions were seen in 9 of these 12 patients; 4 were of the acute type, 5 of the chronic type. Chronic gut inflammation was related to axial inflammatory complaints, inflammatory serum variables, thrombocytosis and sacroiliac radiological abnormalities. A 2nd ileocolonoscopy was performed on 5 of the 12 patients, and a 3rd ileocolonoscopy on 2 of these with persistent synovitis. Gut inflammation and joint inflammation were related; moreover, all 5 patients had chronic inflammatory lesions by the time of the last investigation, one presented with Crohn's disease. The 12 patients were reviewed 3 to 9 years after the first ileocolonoscopy. Four patients were in remission, including the 3 patients with initial normal gut histology. Five patients had developed ankylosing spondylitis (AS), a 6th patient possible AS. Axial inflammatory complaints, a family history of spondyloarthropathies, HLA-B27 positivity, early sacroiliac and peripheral joints radiographic changes, persistence of inflammatory serum variables, thrombocytosis and chronic inflammatory lesions on gut biopsy, are predictive factors in juveniles for evolution to AS. Late onset pauciarticular JCA represents a form of spondyloarthropathy similar to adolescent forms. Persistent gut inflammation could play a role in the pathogenesis of the disease and persistent synovitis.
Adolescent↗
A prospective study of patients with spondyloarthropathy with special reference to HLA-B27 and to gut histology.
Ileocolonoscopy was performed on 357 patients meeting the European Spondylarthropathy Study Group criteria for spondyloarthropathy. HLA loci A, B and C were determined in all patients; HLA-B27 was detected in 196 and was absent in the 161 remaining patients. A number of clinical, laboratory and radiological variables were determined before ileocolonoscopy and compared between the HLA-B27+ and HLA-B27- patients. The HLA-B27+ patients were mainly men, with significantly more family members with spondyloarthropathies. Clinical evidence of tendinitis and uveitis was more frequently found in these patients. Like several authors, we found that these patients were more severely affected since they presented more severe radiological involvement of the sacroiliac joints. Syndesmophytes, bamboo spine and erosive joint lesions were more frequent in this group, the hip involvement being of the concentric type. In HLA-B27+ patients ankylosing spondylitis was more prevalent, while in the B27- patients enterogenic, urogenital or undifferentiated spondyloarthropathy was diagnosed. The HLA-B27- patients experienced more episodes of diarrhea, and Crohn-like inflammatory gut lesions were more frequently seen on ileocolonoscopy. In this group a number of patients probably had a form of subclinical Crohn's disease of which the locomotor symptoms were the only clinical expression.
Adolescent↗
Down-staging prostate cancer. Is it possible by androgen depletion and Mitomycin C therapy?
The study was carried out in order to investigate the possibility of tumor reduction in prostate cancer patients. As a reduction of the primary tumor was observed with hormonal treatment and complete response of soft tissue tumor markers with Mitomycin C, this combined treatment was given in seven patients to evaluate if it was able to down-stage those cases which were thought to be incurable (T3N1-2M0/T4N0-2M0). Although the clinical evaluation suggested a significant down-staging, the explorative lymphadenectomy was unable to confirm this. The proposed treatment is able to reduce the tumor bulk significantly of the primary cancer as well as of its metastases; progression during the treatment was not seen.
Aged↗
Rationale for local toxicity of calcium chelators.
Calcium chelating agents, such as ethylenediaminetetraacetate are toxic to urothelium. Their capacity to form complexes with calcium ions, which is the basis for their chemolytical effectiveness, also determines their toxicity. A decrease of chemolytical effectiveness by prior saturation of the chelator with Ca2+ or by lowering the pH to levels unfavourable for calcium binding significantly diminishes tissue injury. Exchange of Mg2+ ions does not, however, diminish tissue damage. The clinical use of calcium ligands is therefore unsafe.
Animals↗
i(12p) in a near-diploid mature ovarian teratoma.
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Adolescent↗
T-cell receptors in ileal mucosal biopsies of patients with Crohn disease and spondylarthropathy.
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Acute Disease↗
Increased intestinal permeability in ankylosing spondylitis.
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Anti-Inflammatory Agents, Non-Steroidal↗
Spondylarthropathy and gut inflammation: immunopathogenetic mechanisms.
In 62% of patients with spondylarthropathy (SpA) we found clinically unsuspected gut inflammation to feature acute or chronic enterocolitis on ileocolonoscopy. A proportion of patients of the latter group had subclinical Crohn's disease as demonstrated clinically, endoscopically, genetically, histologically and immunopathologically. There is a relation between the activity of the gut inflammation and clinical rheumatic symptoms. A pathogenetic mechanism is increased handling of luminal (bacterial or nutritional) antigen, hence inducing T-cell activation and intestinal inflammation. In ileal mucosal biopsies we showed two different cellular events: increased enterocytic expression of class II molecules in active inflammation and an increase of membranous (M) cells overlying lymphocytes in inflamed mucosa. Although the number of intraepithelial lymphocytes was not increased in inflammation, intraepithelial T lymphocytes had protruding processes in close apposition to the tips of epithelial plasma membranes. Lymphocytes crossing the basement membrane were a frequent finding. These features indicate that the intestinal immune response caused by increased antigen processing in the terminal ileum induces an inflammatory immunocascade responsible for the clinical picture of SpA.
Adolescent↗
Toxicity of litholytic ethylenediaminetetraacetic acid solutions to the urothelium of the rat and dog.
The toxicity to the urothelium of bipotassium ethylene-diaminetetraacetic acid (K2-EDTA) buffered with 0.2 M triethanolamine (TEA) at pH 8 and 8.5 was tested in rats and dogs. Even at a low concentration of 3.125 mM, K2-EDTA is very noxious to the bladder mucosa. This toxicity is not due to the buffer TEA, which is well tolerated. Although buffered K2-EDTA, at pH 8.5 is an excellent chemolytic agent for calcium-containing stones, its clinical use is limited by this toxicity.
Animals↗
Toxicity to the urothelium of calcium chelating agents for chemolysis.
Solutions, based on calcium chelating agents, with excellent prospects as litholytic agents in vitro were tested on toxicity to the mucosa of the bladder of the rat. The following compounds were tested at a concentration of 12.5 mM., buffered with triethanolamine 0.2 M at pH 8 and 8.5: ethylenediaminetetra acetic acid with as cation H2+, Li+, Na+, K+, and Cs+, trans-cyclohexane-1.2 diaminetetra acetic acid (cations H+, Na+, K+), diethylenetriamine penta acetate (cations H+, Na+, K+), disodiumethyleneglycol-bis (2 aminoethyl) tetra acetic acid and disodium hydroxyethylethylenediamine tetra acetate. All agents were found to be very noxious to the bladder mucosa of the rat and are unlikely to be safe for clinical use.
Animals↗
Rectal mucosa damage in rabbits after subchronical application of suppository bases.
The effect of suppository bases on rabbit rectal mucosa was investigated using six triglyceride bases, polyethylene glycol, and a triglyceride base combined with monoglycerides or fatty acids and methyl esters of those acids. Rectal irritation was evaluated and scored according to defined pathological features. "Pure" triglycerides and a triglyceride to which a nonionic surfactant was added caused severe mucosal damage with ulceration and inflammation. Hyperemia was characteristic for irritation by polyethylene glycol suppositories. Mucosal damage by a pure triglyceride combined with monoglycerides or fatty acids and methyl esters of those acids was similar but statistically less pronounced than with all other bases.
Animals↗
Gut inflammation in the spondyloarthropathies: clinical, radiologic, biologic and genetic features in relation to the type of histology. A prospective study.
Ileocolonoscopy was performed on 354 patients with spondyloarthropathies. Histologically, the population could be divided into 145 patients with normal gut histology, 88 patients with acute inflammatory lesions and 121 patients with chronic inflammatory lesions. A number of clinical, biologic, radiologic and genetic variables were determined before ileocolonoscopy. Chronic gut lesions were associated with a family history of ankylosing spondylitis (AS) and Crohn's disease, several episodes of diarrhea, an increased stool frequency, elevated inflammatory serum variables, reduced axial mobility, the presence of sacroiliitis, bamboo spine, destructive joint lesions, a diagnosis of AS and HLA-Bw62 positivity. As the frequency of HLA-Bw62 is also increased in proven Crohn's disease, this would suggest that chronic gut lesions are related to this disease. Acute inflammatory lesions were related to a higher fecal carriage of specific bacteria and to the diagnosis of undifferentiated spondyloarthropathy, especially the enterogenic forms of reactive arthritis. Consequently, these lesions also appear to be related to a bacterially induced gut inflammation. Gut histology was normal in urogenital inflammation and urogenital reactive arthritis, suggesting a different portal of entry for antigens. The 3 histologic pictures of the gut (normal, acute and chronic) inflammation seem to correlate with different clinical, biologic and radiologic manifestations of the disease concept of spondyloarthropathies.
Adolescent↗
Intestinal mucosal permeability in inflammatory rheumatic diseases. II. Role of disease.
Gut permeability as measured by the 51Cr-EDTA resorption test was determined in 56 patients with rheumatoid arthritis (RA), 73 patients with spondyloarthropathies (SpA), 18 patients with inflammatory bowel disease (IBD) and 97 controls (42 patients with no inflammatory rheumatic diseases and 55 healthy controls). Gut permeability was found to be increased in the 3 patient groups, partially due to the intake of antiinflammatory drugs. When only patients not taking these drugs were considered, an increased gut permeability was found in patients with SpA and IBD. In patients with RA gut permeability could not be evaluated as they were all taking antiinflammatory medication. Ileocolonoscopy with biopsies of the gut was performed in 62 of the 73 patients with SpA and disclosed subclinical gut inflammation in 21. No difference in gut permeability was found between patients with or without gut inflammation. However, when the type of gut inflammation was considered, a significant increase of gut permeability was found in patients with chronic gut inflammation compared with patients presenting acute lesions. Our findings again suggest that the chronic gut inflammation seen in SpA is fundamentally different from acute gut inflammation and possibly related to the gut inflammation of IBD.
Adult↗
Major histocompatibility complex class II antigen (HLA-DR) expression by ileal epithelial cells in patients with seronegative spondylarthropathy.
Major histocompatibility complex molecules act as non-specific receptors for antigenic proteins and present them to T-cells. Presented antigen together with class II molecules activates antigen specific T-helper cells and may trigger a cellular immune response. The expression of HLA-DR antigens by epithelial cells was examined with an indirect peroxidase technique in ileal biopsies from 38 patients with seronegative spondylarthropathy and features of acute or chronic gut inflammation on biopsy, 14 patients with chronic inflammatory bowel disease, 10 rheumatic and 10 non-rheumatic controls. In acute ileitis, there was more HLA-DR expression in villous and crypt epithelial cells than in non-inflamed controls (p less than 0.01). In chronic inflammation and in chronic inflammatory bowel disease, class II antigens were more expressed in villus (p less than 0.02) and crypt epithelium (p less than 0.01). Strong HLA-DR expression in crypt epithelial cells was connected with active inflammation (p less than 0.02). These findings suggest binding of unknown enterobacterial or nutritional luminal antigens to HLA-DR antigens normally present in enterocytes. The enterocytes act as antigen presenting cells causing a local increase of targets for activated T-cells and trigger the gut inflammation responsible for the clinical symptoms of the seronegative spondylarthropathy.
Adolescent↗
HLA-B27 positive idiopathic acute anterior uveitis: a unique manifestation of subclinical gut inflammation.
Ileocolonoscopy was performed on 2 HLA-B27 positive patients with idiopathic acute anterior uveitis neither of whom had articular or intestinal complaints. Microscopic examination of the biopsy specimens revealed the presence of chronic inflammatory lesions in the ileum. Since these lesions have also been described in other forms of spondyloarthropathy, we postulate the presence of gut inflammation was related to the uveitis.
Acute Disease↗
Ileocolonoscopy in seronegative spondylarthropathy.
A prospective endoscopic and histologic study of terminal ileum and colorectum in 211 patients with seronegative spondylarthropathy revealed macroscopic inflammatory lesions varying from erythema to superficial erosions in 30% of the patients and microscopic inflammation in 61%. Two types of inflammation were observed: an acute inflammation resembling an infectious enterocolitis and a chronic inflammation. In idiopathic reactive arthritis both types of inflammation were equally present, whereas chronic inflammation predominated in patients with ankylosing spondylitis. In 32% of patients with chronic inflammation, the lesions particularly resembled early Crohn's disease. Repeat ileocolonscopy on 19 patients demonstrated a parallel evolution of joint symptoms and histologic lesions. All patients with acute inflammation went into clinical and histologic remission, whereas lesions persisted in patients with Crohn-like inflammation. In patients with chronic inflammation, remission and persistence were observed equally. This study identified a group of patients with seronegative spondylarthropathy which, even in the absence of gastrointestinal symptoms, showed evidence of gut inflammation, probably inducing an increased gut permeability with transgression of the oral tolerance and absorption of provocative antigens into the circulation. It is also possible that both diseases reflect a common underlying process.
Arthritis↗