On the nature of rheumatism.
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Biomedical subjects
Publications and source records attributed to S R Block.
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OBJECTIVE: To investigate the occurrence and clinical correlation of the arg519-to-cys mutation in the type II procollagen gene in patients with osteoarthritis (OA). METHODS: Sixty-six subjects from 7 families with a strong family history of generalized OA and 13 patients with erosive OA were evaluated clinically and radiologically. Blood samples from 58 subjects in the familial OA group and from all 13 patients with erosive OA were obtained for DNA analysis. Exon 31 of COL2A1, which spans residue 519, was amplified by polymerase chain reaction. RESULTS: The arg519-to-cys mutation was detected in 2 of the 7 families with generalized OA. In these 2 families, the mutation was present in the 2 probands and in 19 other clinically affected family members, as well as in 3 (so-far) clinically unaffected family members (ages 25, 14, and 11 years). It was absent in 18 clinically unaffected members tested. The mutation was associated with a distinctive pattern of early-onset, aggressive, generalized OA with a mild spinal chondrodysplasia. Inheritance was autosomal dominant. No mutation was found in any of the patients with erosive OA. CONCLUSION: The arg519-to-cys mutation defines a new pathogenic factor in generalized OA with characteristic clinical and radiologic features. The demonstration of a mutation in 3 of 8 families with OA studied thus far suggests a significant incidence of genetically related clinical OA.
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Chronic musculoskeletal pain syndromes are common problems, but the etiology, pathogenesis, and pathology of many of them are very poorly understood. Because the currently used nomenclature suggests an understanding that we do not have, I propose that names like "myofascial pain," "tension myalgia," and "FM" be abandoned in favor of the more indefinite (but more honest) terms like "regional" and "generalized rheumatism." No matter what we rheumatologists call it, however, the condition of chronic generalized musculoskeletal pain probably is only one part of an even more generalized condition that includes IBS, chronic headaches, regional migratory numbness, TMJ syndrome, and a whole host of other somatic pain syndromes. The same patients end up seeing many specialists who themselves feel frustrated with the labels at their disposal, and these specialists end up resembling the blind men confronting the elephant. In this regard, the new ACR criteria for the diagnosis of fibrositis, by emphasizing tenderness and ignoring the presence of these other syndromes, are too circumscribed and represent a step backward in our attempts to understand. Although the chronic rheumatisms are problems difficult to manage and frustrating for both the patient and the physician, when patience can be applied and confidence achieved, a positive relationship can result and the patient can be helped.
We attempted a randomized, double blind trial of placebo vs cyclobenzaprine (Flexeril) in 40 female patients with fibromyalgia from a private rheumatology practice in Maine. Patient reports and physician global assessments indicated that cyclobenzaprine was more effective than placebo in alleviating symptoms of fibromyalgia in a subgroup of patients. However, most patients in the study had more accurate perceptions of drug effects than had been predicted and were able to identify the test drug. How much this awareness contributed to the perceived effectiveness of cyclobenzaprine is unknown.
We tested the current criteria for fibromyalgia. Pain tolerance was measured at tender point and control point sites using a pressure algometer, and responses to 6 standard psychological self-reports were obtained from 125 patients with generalized nonarticular rheumatism, rheumatoid arthritis, or osteoarthritis. Among patients with generalized nonarticular rheumatism, published symptom criteria for fibromyalgia did not correlate significantly with the number of tender points. Only lower generalized pressure point pain tolerance distinguished fibromyalgia from other generalized nonarticular rheumatism. Generalized nonarticular rheumatism mean scores were much higher than controls on tests measuring the tendency to report physical symptoms, including headaches and functional bowel syndrome. It is probable that patients with fibromyalgia do not differ in any important physical or psychological respect from other patients with generalized nonarticular rheumatism except for the presence of tender points. However, the presence of tender points is merely a reflection of the patient's general pressure pain sensitivity and is not indicative of any special localized pathological phenomenon. The concept of fibromyalgia as an entity separate from the rest of generalized nonarticular rheumatism may be an artifact of a physician's approach to the patient. Most patients with generalized nonarticular rheumatism demonstrate an abnormally high frequency of reporting manifold disagreeable symptoms and probably come to the attention of many medical disciplines.
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To assess the role of genetic factors in systemic lupus erythematosus (SLE), 12 twon pairs (seven definitely monozygotic, three definitely dizygotic) of which one or both twins had SLE, were studied and compared to 17 twin pairs (12 definitely monozygotic) previously described. In the present series, four of seven (57 per cent) definitely monozygotic pairs were clinically concordant for SLE, satisfying the preliminary criteria of the American Rheumatism Association (ARA). Concordance for the presence of antinuclear factor (ANF) and hypergammaglobulinemia was 71 and tinuclear factor (ANF) and hypergammaglobulinemia was 71 and 87 per cent, respiectively. These data closely agree with those on the 12 definitely monozygotic sets previously described. All three of the dizygotic sets in the present series were discordant for clinical SLE, although one clinically well twin had marked serologic abnormalities. Comparison of these data with thos from other first degree relatives of out twins clearly suggests a strong genetic component in the pathogenesis of SLE. The relative contribution of nongenetic and environmental factors to the expression of the disease is discussed.
Peripheral blood lymphoid cells obtained from nine twin pairs (six monozygotic and three dizygotic) in which one or both twins had systemic lupus erythematosus (SLE) were examined by electron microscopy for the occurrence of two distinctive intracytoplasmic structures-tubuloreticular structures (TRS) and tubular crystalloids (TC). TRS were found in 0.8 to 14.8% of lymphoid-cell cross sections in 9 of 11 twins with SLE and 2 clinically well but serologically abnormal twins. Lymphoid cells of twins both clinically and serologically normal did not exhibit TRS, although their monozygotic or dizygotic SLE-positive counterparts possessed these structures. Thus, the expression of TRS was more consistent with an acquired than inborn trait and appeared to correlate with disease and serologic manifestations of SLE. TC were found in 1.7 to 7.9% of lymphoid-cell cross sections in every twin examined. No correlation was recognized between clinical or laboratory data and the frequency of TC-bearing cells. The significance and the ultrastructural development of TC in the peripheral blood lymphoid cells are briefly discussed.
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