Update on fibromyalgia syndrome.
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Biomedical subjects
Publications and source records attributed to D J Wallace.
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OBJECTIVE: To assess the efficacy of pulse/synchronization cyclophosphamide/apheresis in patients with proliferative lupus nephritis. METHODS: Eighteen patients with Class III or IV renal biopsies and chronicity indices <6 were prospectively randomized to receive 6 courses of parenteral cyclophosphamide over 8 months along with prednisone. Nine of these patients also received 3 daily plasmaphereses prior to each of the 6 courses of cyclophosphamide. Assessments compiled at 6 and 24 months included serum creatinine, albumin, anti DNA, 24-hour urine protein, and C3 complement along with SLAM scores. RESULTS: Two out of nine patients in each group evolved end stage renal disease and 3/9 patients in each group went into a renal remission at 24 months. Serum albumin, C3 complement, and SLAM scores improved in both groups, and anti-DNA improved in the pulse/synchronization patients (P < 0.025). No intergroup comparisons were significant. CONCLUSION: The addition of pulse/synchronization apheresis to cyclophosphamide therapy does not improve the course of patients with proliferative lupus nephritis.
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Twenty-six of 488 (5%) patients with systemic lupus erythematosus followed in a private practice developed clinically evident, symptomatic avascular necrosis. Avascular necrosis was significantly associated with hypertension, pleural effusions, cerebritis, nephritis, anemia, and earlier age of disease onset. No association with anticardiolipin antibodies or thromboembolic disease was observed. Avascular necrosis is usually observed in active, severe lupus.
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Neurones in the cardiac plexus of the guinea-pig were subdivided into three groups according to their electrophysiological properties and subsequently labelled with neurobiotin. Preparations were counterstained with antibodies to synaptophysin to reveal boutons containing synaptic vesicles. Two of the three groups of cells which, in the electrophysiological studies were found to receive excitatory synaptic inputs were associated with numerous synaptophysin positive boutons. Cells of the other group, which did not appear to receive any synaptic inputs were associated with fewer synaptophysin positive boutons. Wholemount preparations were double stained with antibodies to Protein Gene Product 9.5 and synaptophysin. This revealed most neurones, along with vesicle filled boutons. Ganglia generally contained less than 10 neurones with a range between one and over 30. In wholemount preparations it was found that about 90% of the cells were associated with a large number of synaptophysin positive boutons whilst the remaining cells were associated with very few synaptophysin positive boutons. These results are consistent with the idea that a proportion of cardiac ganglion cells fail to receive a synaptic input and suggest that by staining wholemount preparations of guinea-pig cardiac plexus with antibodies to synaptophysin it is possible to differentiate between groups of cells which receive a synaptic input and those which fail to receive a synaptic input. Approximately 10% of intrinsic cardiac neurones appear to lack a synaptic input.
Genetic susceptibility confers significant risk for systemic lupus erythematosus (SLE). The MHC region and other polymorphic loci have been associated with SLE. Because more compelling evidence for an involvement of a genetic locus includes linkage, we tested a candidate region homologous to a murine SLE susceptibility region in 52 SLE-affected sibpairs from three ethnic groups. We analyzed seven microsatellite markers from the human chromosome 1q31-q42 region corresponding to the telomeric end of mouse chromosome 1, the region where specific manifestations of murine lupus, including glomerulonephritis and IgG antichromatin, have been mapped. Comparing the mean allele sharing in affected sibpairs of each of these seven markers to their expected values of 0.50, only the five markers located at 1q41-q42 showed evidence for linkage (P = 0.0005-0.08). Serum levels of IgG antichromatin also showed evidence for linkage to two of these five markers (P = 0.04), suggesting that this phenotype is conserved between mice and humans. Compared to the expected random distribution, the trend of increased sharing of haplotypes was observed in affected sibpairs from three ethnic groups (P < 0.01). We concluded that this candidate 1q41-q42 region probably contains a susceptibility gene(s) that confers risk for SLE in multiple ethnic groups.
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The term fibromyalgia describes a complex syndrome characterized by pain amplification, musculoskeletal discomfort, and systemic symptoms. Although its existence has been controversial, nearly all rheumatologists now accept fibromyalgia as a distinct diagnostic entity. In fact, in the United States it is the third or fourth most common reason for rheumatology referral. Exciting new insights into the aetiology, pathogenesis, diagnosis and treatment of fibromyalgia will be reviewed.
OBJECTIVE: To evaluate the ability of hydroxychloroquine sulfate (HCQ) to extend the response to combination therapy with HCQ and methotrexate (MTX) and the safety of longterm HCQ maintenance therapy in patients with active rheumatoid arthritis (RA). METHODS: Two-part study consisting of an open label segment evaluating combination HCQ/MTX therapy followed by a double blind segment evaluating maintenance therapy for a total of 60 weeks. First, all patients were treated with HCQ 400 mg/day and MTX 7.5 to 15 mg/week for 24 weeks. Then, responders were randomized into 3 groups: (1) HCQ with MTX as needed for disease flare (n = 40), (2) HCQ 400 mg/day (n = 41), or (3) placebo with MTX as needed for disease flare (n = 40), each for 36 weeks. RESULTS: Clinical disease and laboratory variables improved significantly during initial combination therapy with HCQ and MTX. After MTX withdrawal, HCQ-containing maintenance regimens delayed the onset of disease flare (p = 0.023). There were no unexpected adverse events at any time or between-group differences in the distribution of adverse events during the double blind segment. CONCLUSION: Combination of HCQ and MTX appeared to be effective and well tolerated for 24 weeks. After withdrawal of MTX, HCQ extended the response seen with combination therapy and was well tolerated for 36 weeks. Initial therapy with HCQ and MTX, followed by maintenance HCQ, may be a useful alternative for the treatment of RA.
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The causes of the aberrant constitutive expression of cytokines in SLE have not been elucidated yet, but alterations in cytokine gene structure could be a contributing factor. By RFLP (Restriction Fragment Length Polymorphism) analysis of genomic DNA, we found a higher incidence of allelic, higher MW XbaI bands in the IL-6 genes of 9/57 SLE patients vs 1/36 unrelated controls (p = 0.05) HLA DR/DQ typing of the polymorphic patients revealed they were all DQ beta 6. The study of one family indicated that the XbaI polymorphic patient and her polymorphic unaffected offspring had higher than normal levels of constitutive IL-6 mRNA. The SLE-associated IL-6 XbaI restriction alleles had duplications of AT-repeat sequences, approximately 500 bp downstream of the 2nd polyadenylation site, in an AT-rich mini-satellite with similarities to Matrix Associated Regions (MARs), that may be important in DNA replication and in gene expression. These are novel observations that suggest that, in SLE, there is increased variability in the 3' flanking region of the IL-6 gene. This variability may be related to the aberrant IL-6 expression that was reported by us and others in this disease.
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