The pathogenic role of anti-neutrophil cytoplasm autoantibodies.
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Biomedical subjects
Publications and source records attributed to O Meyer.
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Bilateral symmetrical polyarthritis occurred in three patients (2 males and 1 female), with no previous history of inflammatory rheumatologic disease, given alpha-interferon for 1 1/2, 7, and 10 months as treatment of chronic non A-non B hepatitis, myelofibrosis, and thrombocytopenia with myeloproliferative disorder, respectively. Joint manifestations developed 1 1/2, 3, and 10 months after initiation of alpha-interferon in a dosage of 3.10(6) U three times a week, 4.5.10(6) U per day, and 8.10(6) U three times a week. Polyarthritis persisted following withdrawal of alpha-interferon in the two last patients of whom one had rheumatoid nodules and positive rheumatoid serology and the other had scleritis, exanthema, and negative rheumatoid serology. Erosive rheumatoid arthritis was diagnosed after 28 months and 12 months, respectively, in two patients who required systemic corticosteroids with antimalarials (1 case) or azathioprine after failure of methotrexate (one case). Follow-up in the third case (12 months) is too short to allow differentiation of systemic lupus erythematosus (ANA: 1/1500 H with anti-DNA antibodies 58 U/ml) and chronic autoimmune hepatitis. Reports of chronic inflammatory rheumatologic disease during alpha interferon therapy are exceedingly few in number. In the cases reported herein, alpha-interferon may have either triggered or revealed the joint disease. To prevent occurrence of this complication, exclusion from alpha-interferon therapy of patients with autoantibodies or a positive history for clinical evidence of immune dysfunction may be considered.
We describe 7 Achilles tendinitis occurring during fluoroquinolone treatment. Antibiotic agents used were pefloxacin and ofloxacin. In 3 cases the course was complicated by rupture of the tendon, one of which is histologically documented. The toxic effects of quinolones on tendon is discussed.
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To date, descriptions of bone manifestations associated with the acquired immunodeficiency syndrome (AIDS) have mostly been limited to case reports. Six such cases observed in our Departments of Rheumatology and Infectious Diseases, are reported. Three types of manifestations were observed: malignant lymphoma, infectious osteomyelitis, and reflex sympathetic dystrophy syndrome (algoneurodystrophy) secondary to central nervous system involvement.
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The purpose of this study was to establish the actual survival rate of a cohort of 51 patients with systemic lupus erythematosus (SLE) all of whom were followed during 12 years from 1976 to 1988 and to evaluate the prognostic significance of the severe complications of the disease. Forty-eight were females. The mean age was 28.5 at onset, 36.2 at diagnosis and 42 at entry; 80% had four or more 1982 ARA criteria at diagnosis and 96% in 1988. Survival rates were: 96% at two years, 86.3% at five years and 74.5% at twelve years. The main cause of death was infection (62%); SLE was directly responsible in only one case. Manifestations considered as severe occurred in almost two-thirds of the cases without any concordance in the time sufficient to recognize different severe forms of the disease.
We report three cases of systemic lupus erythematosus (SLE) associated with necrotizing histiocytic lymphadenitis (Kikuchi's disease) and immunologically proven human parvovirus B19 infection. Simultaneous occurrence of SLE and Kikuchi's disease was a characteristic of the three cases. Kikuchi's disease is an uncommon disease that usually affects young women and is characterized by painless unilateral cervical lymph-node enlargement. T-cell regions of affected lymph nodes are exclusively involved with patchy paracortical necrosis surrounded by a polymorphous cell population of histiocytes and macrophages. However, lymphadenopathy in patients with SLE may be histologically indistinguishable from Kikuchi's necrotizing lymphadenitis. The cause of Kikuchi's disease remains uncertain, although infectious agents have been proposed. A positive IgM-specific anti-human parvovirus B19 antibody test in our three cases suggests that B19 can induce a necrotizing histiocytic lymphadenitis and possibly a clinical SLE flare. High-dose (1 mg/kg/day) and medium-dose (0.5 mg/kg/day) oral prednisone was an effective treatment for constitutional and visceral symptoms of Kikuchi's and SLE diseases.
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Florid necrotizing lymphadenitis, characterized by segmental infarction and lymphoid hyperplasia, is an uncommon feature of systemic lupus erythematosus (SLE). Kikuchi's disease is a well-defined clinicopathological entity, with a strong preference for the cervical lymph nodes of young women. The etiology of histiocytic necrotizing lymphadenitis (HNL) remains unknown, although viral agents have been proposed. HNL may reflect a self-limited SLE-like autoimmune disease but full-blown SLE associated with this condition has not, to the best of our knowledge, been reported. Thus, ours is the first description of the coexistence of SLE and HNL in 3 patients with immunologically proven parvovirus B19 infections. SLE and HNL were diagnosed simultaneously in 2 patients, but was retrospective in the third, in whom anti-tuberculous therapy was ineffective. Patients 1 and 2 were treated with prednisone (1 mg/kg/d) and responded rapidly. These data suggest that both HNL and SLE flares can be caused by parvovirus B19 infection.
Antiphospholipid antibodies can be detected by three methods; agglutination reactions with a cardiolipid antigen (VDRL, Kline, Kolmer) as observed in false positive syphilitic serologies; secondly coagulation reactions using thromboplastin (activated cephalin time, diluted thromboplastin time, Stipven time...). These cases are called lupus-like or, better, antiprothrombinase circulating antibody; finally, solid phase immunological tests (ELISA, RIA) with purified phospholipids, usually cardiolipin. The antiphospholipid antibodies detected by this method are not the same and the percentage of concordance between the two tests does not exceed 50 per cent. These antibodies are present in 30 to 60 per cent of patients with disseminated lupus erythematosus and also, less frequently, in other connective tissue disorders. They are always found in the so-called primary antiphospholipid syndrome, featuring recurrent venous or arterial thrombosis, repeated abortion, thrombocytopenia, and often a livedo reticularis and leg ulceration. Arterial thrombosis may occur in any part of the body (eye, central nervous syste, visceral or peripheral arteries). Mortality is related to neurological or coronary complications. The pathogenicity of antiphospholipid antibodies has not been formally demonstrated, but they could interact with membrane phospholipids of the vascular endothelium and/or platelets. Immuno-suppressor therapy is not very effective and long-term anticoagulant and/or platelet antiaggregant therapy is usually required.
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Among soluble anti-nuclear antigen auto-antibodies, anti-Ro(SS-A) were, for unknown reasons, difficult to detect by immunoimprint (II). The aim of this study was the development of a method of preparation of Ro(SS-A) antigen enabling greater sensitivity in the detection by II of the corresponding antibodies, then application of this method in a series of 63 cases of primary Sjögren's syndrome in order to study the clinical significance of anti-Ro(SS-A) antibodies. Ro(SS-A) antigen was prepared from human spleen and partially purified on DE-52 resin. The protein extract prepared reacted in II with reference anti-Ro(SS-A) and anti-La(SS-B) antibodies. The series of 63 cases of primary Sjögren's syndrome (57 F, 6M) included 50 of extraglandular primary Sjögren's syndrome and 13 of isolated glandular primary Sjögren's syndrome. Twenty two cases of primary Sjögren's syndrome had anti-Ro(SS-A) (35%). Twenty patients had anti-Ro(SS-A) by II (32%) and 17 by double diffusion in agar (27%) (p = NS). Among 7 discordant sera, 2 were not detected by II. The incidence of anti-Ro did not differ statistically between the extraglandular (40%) and glandular (15%) primary Sjögren's syndrome groups. Patients were divided into two groups according to whether they did (n = 22) or did not (n = 41) produce anti-Ro(SS-A).(ABSTRACT TRUNCATED AT 250 WORDS)
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The reproductive effect of N,N-dimethylformamide (DMF) administered epicutaneously to rats was examined. The rats were dosed on gestation days 6-15 or on gestation days 1-20 at dose levels of up to 2 ml DMF kg-1 body weight. Body weight, weight gain and pregnancy rate were reduced in those rats receiving 2 ml DMF kg-1 body weight per day on days 6-15. A reduction in the number of live fetuses and in fetal weight, as well as an increase in postimplantation loss, were also observed at this dose level. Similar but more pronounced effects were observed in rats dosed on days 1-20 with 2 ml DMF kg-1 body weight. The lowest effect level was 1 ml DMF kg-1 body weight. No other dose-related effects were found in this study.
The pterin cofactor (bactopterin) in the molybdoenzyme CO dehydrogenase isolated from Pseudomonas carboxydoflava has previously been shown to differ from molybdopterin in molecular mass, phosphate content, stability, and other properties, implying a novel structure. The structure of the CO dehydrogenase pterin has been investigated in the present studies by alkylation and isolation of the carboxamidomethyl derivative. The alkylated pterin was identified as [di-(carboxamidomethyl)]molybdopterin cytosine dinucleotide on the basis of its absorption properties and by degradation with nucleotide pyrophosphatase yielding carboxamidomethylmolybdopterin and CMP. Further treatment of these products with alkaline phosphatase produced species with absorption and chromatographic properties identical to those of the corresponding dephospho compounds. Molybdopterin cytosine dinucleotide is the second molybdopterin variant to be structurally characterized. The fact that molybdopterin cytosine dinucleotide and molybdopterin guanine dinucleotide contain molybdopterin in their structure shows that the pterin moiety, with its unique dithiolene-containing sidechain, is a structural element which is common to the organic portion of the molybdenum cofactors of many molybdoenzymes.