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Objective: To assess radiographically determined disease progression in patients in the Minocycline in Rheumatoid Arthritis (MIRA) Trial., Methods: A double blind, randomized, multicenter, 48 week trial of oral minocycline (200 mg/day) or placebo in 6 clinical centers in the United States. Patients include 219 adults with active RA previously receiving limited treatment with disease modifying drugs. Posteroanterior films of the hands from baseline and final visits, blinded for sequence, were read for erosions and joint space narrowing by trained observers. Outcomes included rate of disease progression (change/month) and percentage of patients with progression from baseline, newly involved joints, and newly erosive disease., Results: Using intent-to-treat analyses, progression rates for erosions (0.11 +/- 0.42 minocycline, 0.17 +/- 0.41 placebo; p = 0.47) and joint space narrowing (0.16 +/- 0.55 minocycline and 0.23 +/- 0.71 placebo; p = 0.14) were similar. (Power 43% to detect a 50% difference.) Newly erosive joints occurred more frequently in the placebo group (44 vs 32%; p = 0.08), not a statistically significant difference., Conclusion: Radiographic measurement of disease progression using 4 measures failed to show a significant difference between minocycline and placebo treatment, although for all methods there was a trend toward treatment benefit, consistent with reported clinical results. A one year trial duration, high measurement variability, and slow rate of radiographic progression in this cohort may explain the low power to detect a treatment effect. The measurement that denoted "newly involved" joints was most sensitive in detecting change. In future trials longer term assessment (minimum 2 years) of radiographic changes and further comparison of measures of disease progression are warranted.

To continue its mission of providing information to improve understanding of health care in Michigan and to aid in planning and decisionmaking, the Michigan Health Care Data Corporation needs to achieve several things. The following is a look at its history and structure, MSMS participation, public reports, and future expectations.

Some authors have stated that nail pitting never occurs in Reiter's syndrome. The case of a patient with incomplete Reiter's syndrome with nail pitting and HLA-A2, 28; B18, 27 is presented. Patients who have both psoriasis and Reiter's syndrome have demonstrated increased frequency of HLA-A2 and B27 and markedly decreased frequency of HLA loci associated with psoriasis. The particular finding of nail pitting is presented to illustrate that this change may occur in Reiter's syndrome and may reflect a predisposition to the development of psoriasis or psoriasiform lesions conferred by HLA-A2 with B27, as suggested by previously reported HLA typing studies.

The benefit-to-risk ratios of fenoprofen (2.4 gm/day) and aspirin (3.9 gm/day) were compared in a randomized, double-blind, 26-week parallel study involving 216 patients. Criteria for inclusion, exclusion, subjective, and objective evaluations were based on the PMA-FDA Nonsteroidal Anti-Inflammatory Drug Clinical Testing Guidelines. Thirty-four of 109 aspirin-treated patients and 23 of 107 patients on fenoprofen dropped out of the study. Both fenoprofen and aspirin brought about improvement in most efficacy parameters measured, but fenoprofen was superior to aspirin (p less than 0.05) in reduction of swollen joints, grip strength, activity index, and patients' preference of medication. The number and frequency of complaints and the incidence of abnormal SGOT levels, were greater with aspirin than with fenoprofen. The study suggests that fenoprofen has a better benefit-to-risk ratio than aspirin, when given in equally effective doses.

Three experiments were conducted to evaluate the rater reliability for scoring osseous defects (articular erosions) and joint space narrowing (cartilage destruction) in patients with rheumatoid arthritis. The experiments show that two raters, using different techniques, obtain similar scores; the scores differing primarily by a multiplicative factor. A single rater achieves reproducible results under similar conditions. But with a change in reading technique, such as using a magnifying lens and intense light, the same rater obtains a change in scores. The problems of measurement must be carefully examined for any proposed measurement technique. The superficial objectivity and precision of a measurement scale are less important than its objectively and precision of a measurement scale are less important than its objectively evaluated reliability. Comparing alternative procedures is a statistical problem, and can be subjected to suitable statistical analysis to evaluate alternatives.

We demonstrated the simultaneous occurrence of psoriatic arthropathy and the 2 major types of crystalline arthritis--pseudogout and gout. The crystals found within aspirated synovial fluid and exudative leukocytes were unequivocally identified using the compensating polarizing microscope as calcium pyrophosphate dihydrate in one case and sodium monourate in the other. The surface topography of the intracellular sodium monourate crystals were also displayed.

A 61-year-old man had a tophus on the third finger of his right hand. There was no history of arthritis, no laboratory abnormality, and no chondrocalcinosis. Crystalline material from the tophus was identified as calcium pyrophosphate dihydrate by x-ray diffraction.

This double-blind multicenter study compares the effect of adding auranofin (AF) 3 mg bid or placebo to patients already taking nonsteroidal antiinflammatory drugs for rheumatoid arthritis. The 242 patients who completed 3 months of therapy demonstrated that the group receiving AF responded better than those receiving placebo. Of the 144 patients who completed 6 months coded medication, the efficacy in the AF group was superior to the placebo group in several parameters including a reduction in the number of painful or swollen joints, grip strength, dropout rate, and global efficacy as judged by the evaluating physician. A significant lowering of the Westergren erythrocyte sedimentation rate and immunoglobulin levels was noted in the AF treated patients. This study includes data summarizing the difference between both groups with respect to on-therapy conditions and toxicity.

We utilized a standardized in vitro method which employs transmission electron microscopy to monitor the degree of surface activation (cytoplasmic spreading) and amount of aggregation displayed by platelet populations from 314 patients with one of five distinct rheumatic diseases and from 72 normal subjects. The percentage of patients in each group whose platelet populations were hyperactive was as follows: polymyalgia rheumatica, 75 percent; scleroderma, 65 percent; primary gout, 61 percent; rheumatoid arthritis, 57 percent; and degenerative joint disease, 40 percent. Pair-wise contrasts performed after an analysis of variance suggest the following differences and similarities: (1) the mean differential platelet count of the normal subjects differed from that in each disease state; (2) the platelet responsivity in patients with degenerative joint disease most closely resembled that in normal subjects; (3) the platelet response in polymyalgia rheumatica plus temporal arteritis was the most abnormal; and (4) platelet response in scleroderma, rheumatoid arthritis, and gout closely resembled each other. The increased platelet response in vitro may reflect the in vivo presence of disease-related "risk factors" (hyperuricemia, immune complexes, and atherosclerosis). Those patients with "triggered" platelet populations may be appropriate candidates for antiplatelet therapy.

Forty-one coded radiographic films from 16 patients with rheumatoid arthritis were read by 13 observers, using 4 different methods for scoring abnormalities. Although absolute scores differed widely among individual observers, correlation coefficients were greater than 0.850 for approximately 2 of 3 comparisons. When films were ranked, using the median rank of all readers, 72% of individual ranks were within 10% of the median ranks. Among serial films on individual patients, 92% of comparisons between early and late films were interpreted as demonstrating progression of abnormalities when mean standardized scores showed an increase in scores of 15 units or greater. Films with lesser changes were interpreted inconsistently. This study shows good general agreement among readers in scoring radiologic abnormalities of hands and wrists, when applied to a film set showing a broad spectrum of severity, and defines the sensitivity of radiologic detection of disease progression.

Numerous methods for reading abnormalities of rheumatoid arthritis in hand and wrist radiographs have been proposed over the past several decades. There are many differences among these methods, one of the more striking of which is the variation in the number of joints that are scored. In this study, we tested the number of joints that need to be read in order to represent abnormalities accurately and reproducibly, using the scores of multiple observers. Thirteen rheumatologists and radiologists each read a set of 41 hand and wrist films from patients with rheumatoid arthritis. Ten of 13 readers scored 27 joints in each hand and wrist; the other 3 readers scored fewer areas. Fourteen combinations of joints were selected based on the frequency of involvement and the technical adequacy of routine films in assessing a given area. After testing these 14 different combinations, 1 scheme, which included 17 areas read for erosions and 18 areas read for joint space narrowing, was tested further. The correlation coefficients for 10 intraobserver scores derived from this modified scheme compared with the original scores were between 0.981 and 0.997. Seventy-one of 78 interobserver comparisons were better using the new scheme than using the original scheme. These data indicate that the simplified scheme, using a combination of 17 joints to score erosions and 18 to score joint space narrowing, more accurately reflects the extent of abnormalities perceived by a panel of experts than does the original scheme. This abbreviated number of joints shortens the amount of time required to read a set of films and simplifies the scoring of films, since a number of areas that are difficult to read are eliminated from radiographic assessment.

Radiologic assessment of progressive joint destruction in rheumatoid arthritis is generally considered to be the ultimate standard for evaluation of treatment. We compared alternative radiologic techniques by performing a randomized, controlled trial in which hand films of rheumatoid arthritis patients were read by several skilled observes. The number of joints evaluated (34 versus 18) was found to make relatively little difference, but the number of readers and their experience level was critical. Films should be read in pairs. Joint space narrowing and erosion scores were shown to contribute independent information. Use of recommended techniques can reduce the number of patients required and, thus, can reduce the cost of a clinical trial by more than half and can substantially increase the sensitivity and efficiency of a trial. Therefore, critical selection of the method of assessing study endpoint is of great importance.

The discovery of chrysotherapy occurred 90 years ago. Gold salts (GS) as an antibacterial agent were used initially for tuberculosis (TB), but an infectious etiology was also suspected for rheumatoid arthritis (RA). Patients who received GS for TB and who also had RA noted improvement of their arthritis. The injectable GS regimen now commonly used evolved from the empirical use of GS for RA from 1920-1960. Originally, clinical experience perpetuated the use of injectable GS to modify RA and its progression. However, scientific data obtained in the last 2 decades have supported the efficacy of chrysotherapy. Studies of protein binding, blood and serum concentrations, tissue distribution, and the toxicity of GS all provided suggestions for its mode of action. As chemical and cellular mediators of inflammation were uncovered, the possible actions of gold have been refined. Because the immune system seems to perpetuate rheumatoid inflammation, the interactions with GS continue to be studied. The in vitro and in vivo actions of GS with the immune system so far have provided conflicting data for its immunological effect. Studies by models of mucosal immunity may lead to new insights in the mode of action for gold.

Our study of 39 patients with rheumatoid arthritis suggests a trend for benoxaprofen therapy given over a prolonged period to retard the rheumatologic process when measured radiologically by both osseous defect and joint space narrowing rates. After a mean duration of 21 months, the progression of osseous defects (OD) and/or joint space narrowing (JSN) was decreased in 28 of 39 patients (72%) who qualified for this study. Fourteen patients (36%) had both OD and JSN rates decreased. An additional 8 patients had OD rate diminished alone and another 6 patients had JSN decreased alone. Clinical evaluation of benoxaprofen has previously revealed a low risk factor and an ability to improve clinical symptoms and signs. Because there is also a trend for this drug to retard or arrest radiologic progression, it becomes a promising agent for the long-term treatment of rheumatoid arthritis.