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Measurements of tophus size can be important in monitoring the course of gout therapy, as tophus resolution is proposed as one measure of success of treatment. This multicentre study assessed the intra- and interreader reproducibility of quantitative tophus volume measurements from magnetic resonance images (MRI) in subjects with palpable gouty tophi. Subjects first underwent radiographic imaging of a selected tophus followed by MRI before and at ≤5, 10 and 20-min after gadolinium administration. After choosing optimal parameters, subjects underwent pre- and postgadolinium-enhanced MRIs of a selected tophus on two occasions separated by 5–10 days. Unenhanced spin-echo images provided satisfactory tophi images and were less subject to interfering artefacts than gadolinium-enhanced gradient-echo images. Intrareader reproducibility was excellent, with no statistically significant difference in mean tophus volume between visits (mean difference − 0.05 ± 0.97 cm3). A small but statistically significant difference in interreader mean tophus volume was detected (mean difference 0.89 ± 2.05 cm3; p < 0.05). MRI can quantify tophus size in gout and deserves further comparison with other techniques for tophus size monitoring in assessing effects of gout therapy. [ABSTRACT FROM AUTHOR]

Objective: To characterize histologic alterations and inflammatory infiltrates in the synovium of patients with chronic septic arthritis (SeA)., Methods: Synovial membranes from patients with SeA (9 specimens; disease duration >4 weeks) were compared with specimens from patients with septic joint prosthesis loosening (septic total arthroplasty [SeTA]; 9 specimens), rheumatoid arthritis (RA; 25 specimens), osteoarthritis (25 specimens), and normal histology (10 specimens). Sections were stained with hematoxylin and eosin, tissue gram stain, and immunostains for von Willebrand factor (vWF; blood vessels), Ki-67 (dividing cells), CD15 (neutrophils), CD3 (T cells), CD20 (B cells), CD38 (plasma cells), and CD68 (macrophages)., Results: Gram stains were positive in all SeA and SeTA specimens. Mixed polymorphonuclear and mononuclear infiltrates predominated in SeA and SeTA. SeA could be differentiated from RA by higher densities of CD15+ cells (SeA:RA ratio 6.5:1; P < 0.001) or Ki-67+ cells (ratio 2.1:1; P = 0.012). The inflammatory infiltrate of SeTA was similar to SeA but contained fewer CD3+ cells (SeTA versus SeA 0.26:1; P = 0.009) and a tendency toward fewer CD20+ cells. Mean vascular density was strikingly increased in SeA (SeA:normal ratio 3.0:1; P < 0.001) and, to a lesser extent, in the vascularized areas of the SeTA specimens (SeTA:normal ratio 1.9:1). Ki-67/CD31 double immunostains demonstrated proliferating endothelial cells in small subintimal blood vessels, suggesting angiogenesis. Receiver operating characteristic curve analysis identified higher densities of CD15+ and Ki-67+ cells and vWF-positive vessels as histologic markers that differentiated SeA from RA., Conclusion: This first analysis of the synovium in patients with chronic pyogenic arthritis identified dramatic neovascularization and cell proliferation, accompanied by persistent bacterial colonization and heterogeneous inflammatory infiltrates rich in CD15+ neutrophils, as histopathologic hallmarks.

Objective: We and others have reported the presence of Chlamydia and other bacterial species in joint specimens from patients with reactive arthritis (ReA). The present study was conducted to investigate whether bacteria other than those specified by diagnostic criteria for ReA could be identified in synovial fluid (SF) or tissue from patients with various arthritides, and whether the presence of such organisms corresponds to particular clinical characteristics in any patient set or subset., Methods: DNA in synovial biopsy samples and SF obtained from 237 patients with various arthritides, including ReA, rheumatoid arthritis, and undifferentiated oligoarthritis, was assayed by polymerase chain reaction (PCR) using "panbacterial" primers; we chose only samples known to be PCR negative for Chlamydia, Borrelia, and Mycoplasma species. PCR products were cloned, and cloned amplicons from each sample were sequenced; DNA sequences were compared against all others in GenBank for identification of bacterial species involved., Results: Ten percent of patient samples were PCR positive in panbacterial screening assays. Bacterial species identified belonged to the genera Neisseria, Acinetobacter, Moraxella, Salmonella, Pseudomonas, and others. Thirty-five percent of PCR-positive patients showed the presence of DNA from more than a single bacterial species in synovium; overall, however, we could identify no clear relationship between specific single or multiple bacterial species in the synovium and any general clinical characteristics of any individual or group of patients., Conclusion: This analysis provides the first systematic attempt to relate bacterial nucleic acids in the synovium to clinical characteristics, joint findings, and outcomes. Many patients with arthritis have bacterial DNA in the joint, and, in some cases, DNA from more than a single species is present. However, except for 1 case of a control patient with staphylococcal septic arthritis, it is not clear from the present study whether the synovial presence of such organisms is related to disease pathogenesis or evolution in any or all cases.

Acute erythroleukemia (FAB M6) is a rare heterogeneous disease with an increase in red cell precursors and myeloblasts. Three subsets have been described: M6A (myeloblast-rich erythroleukemia); M6B (proerythroblast-rich erythroleukemia); and M6C (myeloblast- and proerythroblast-rich mixed variant). This study was undertaken to define and compare the clinical courses and survival outcomes among M6A, M6B, and M6C variants of erythroleukemia. Sixty-nine cases of M6 leukemia were categorized as consisting of >/=50% erythroid of all nucleated cells and M6A with >/=30% myeloblasts/nonerythroid component; M6B with >/=30% proerythroblasts/erythroid component; and M6C with >/=30% myeloblasts and >/=30% proerythroblasts. The demographics, cell type distribution, and survival (mean +/- sd) of these groups were compared. There were 32 M6A, 26 M6B, and 11 M6C patients. No significant difference was seen among the groups in age, sex, or treatment. Compared to M6A, both the M6B (P< 0.0001) and M6C (P< 0.0001) variants showed a statistically significant increase in the percentage of bone marrow erythroid cells, proerythroblasts, and the proerythroblasts/erythroid ratios. Comparing the groups for survival, M6B (3 +/- 3.6 months) versus M6A (25 +/- 28 months), P< 0. 002, and M6C (10 +/- 13 months) versus M6A, P< 0.01 had a poorer prognosis. Calculating the proerythroblasts as a component of total bone marrow erythroids provides a complimentary method for delineating the pure red cell erythroleukemia (M6B) and mixed variant (M6C), similar to that for the myeloid/erythroid (M6A) leukemia. Now that it is possible to delineate erythroleukemia subtypes, innovative treatments are indicated to target the malignant erythroid population, which is resistant to myeloid-based therapies., (Copyright 2000 Wiley-Liss, Inc.)

This report describes the case of a patient with multicentric reticulohistiocytosis. Immunohistochemical analysis revealed prominent markers of monocyte/macrophage origin, as well as the presence of tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-12; the occurrence of the latter in this disease has not previously been reported. Clinical, laboratory, radiographic, and histologic findings in multicentric reticulohistiocytosis are reviewed. In addition, all published cases of multicentric reticulohistiocytosis which included reports of cytokine and immunohistochemical analysis are reviewed, and evidence for a monocyte/macrophage origin and role in disease pathogenesis is provided.

Objective: To evaluate the efficacy and safety of the Prosorba column as a treatment for rheumatoid arthritis (RA) in patients with active and treatment-resistant (refractory) disease., Methods: A sham-controlled, randomized, double-blind, multicenter trial of Prosorba versus sham apheresis was performed in patients with RA who had failed to respond to treatment with methotrexate or at least 2 other second-line drugs. Patients received 12 weekly treatments with Prosorba or sham apheresis, with efficacy evaluated 7-8 weeks after treatment ended. Patients were characterized as responders if they experienced improvement according to the American College of Rheumatology (ACR) response criteria at the efficacy time point. A data safety monitoring board (DSMB) evaluated interim analyses for the possibility of early completion of the trial., Results: Patients in the trial had RA for an average of 15.5 years (range 1.7-50.6) and had failed an average of 4.2 second-line drug treatments prior to entry. After the completion of treatment of 91 randomized patients, the DSMB stopped the trial early due to successful outcomes. Of the 47 patients in the Prosorba arm, 31.9% experienced ACR-defined improvement versus 11.4% of the 44 patients in the sham-treated arm (P = 0.019 after adjustment for interim analysis). When results from 8 additional patients, who had completed blinded treatments at the time of DSMB action, were added to the analysis (n = 99), results were unchanged. The most common adverse events were a short-term flare in joint pain and swelling following treatment, a side effect that occurred in most subjects at least once in both treatment arms. Other side effects, although common, occurred equally as frequently in both treatment groups., Conclusion: Apheresis with the Prosorba column is an efficacious treatment for RA in patients with active disease who have failed other treatments.

Objective: To assess the presence of Chlamydia pneumoniae DNA in the joints of patients with reactive arthritis (ReA) and other arthritides., Methods: DNA was prepared from synovial tissue (ST) and several synovial fluid (SF) samples from 188 patients with either ReA, undifferentiated oligoarthritis, or other forms of arthritis, and from 24 normal (non-arthritis) individuals. Preparations were screened using polymerase chain reaction (PCR) assays that independently targeted the C. pneumoniae 16S ribosomal RNA and major outer membrane protein genes., Results: Twenty-seven of 212 ST samples (12.7%) were PCR positive for C. pneumoniae DNA; 10 SF samples from these 27 patients were similarly positive. Among the PCR-positive patients, 3 had ReA, 2 had Reiter's syndrome, 7 had undifferentiated oligoarthritis, 4 had undifferentiated monarthritis, 6 had rheumatoid arthritis, and 5 had other forms of arthritis. No samples from normal control individuals were PCR positive., Conclusion: DNA of C pneumoniae is present in synovial specimens from some arthritis patients. The prevalence of this organism in the joints was lower than that of C trachomatis, and synovial presence of the organism was not associated with any distinct clinical syndrome. Widely disseminated nucleic acids such as those of C. pneumoniae might have some role in the pathogenesis of several arthritides, since the organism was not found in the ST from normal control individuals.

Objective: To determine how HLA alleles are associated with the clinical disease patterns of patients with synovitis of recent onset., Methods: The HLA alleles A, B, C, DRbeta1, and DQbeta1 were determined in a cohort of 211 patients (mean age 42 years, 64% female, 79% white) with recent-onset synovitis in 1 or more peripheral joints. At a mean disease duration of 33 weeks, 98 patients (46%) met the American College of Rheumatology (ACR) criteria for rheumatoid arthritis (RA), 38 (18%) met the European Spondylarthropathy Study Group criteria for spondylarthropathy (SpA), and 75 (36%) were classified as having undifferentiated arthropathy (UA). Controls were racially matched healthy individuals (n = 244)., Results: Shared epitope (SE) alleles were significantly more common in rheumatoid factor-positive (RF+) patients fulfilling the ACR RA criteria than in other patients with early arthritis (65% versus 35%; P < 0.001). In addition, the RA patients had by far the highest frequency of radiographic erosions (52% and 39% in RF+ and RF- RA, respectively, versus 3% and 9% in SpA and UA patients, respectively; P < 0.0001). The presence of SE alleles was a particularly strong predictor of early erosions in the RF- RA patients (odds ratio [OR] 6.8, 95% confidence interval [95% CI] 1.2-45). The presence of 2 SE alleles or an associated DQbeta1*0301 (DQ7) or DQbeta1*0302 (DQ8) allele appeared to modestly increase the risk of early erosions, although these DQ alleles were in strong linkage disequilibrium with DRbeta1*0401, both in the patient and in the control populations. B27 was linked with the presence of SE alleles in the patients, including those patients fulfilling the RA criteria, but not in the controls (12% versus 3%; P < 0.001). Enthesitis was present in 23 (11%) of 211 patients, was highly associated with B27 (OR 4.2, 95% CI 1.5-11.5), and surprisingly, was not a feature specific only to the SpA group. The B8-DR3 haplotype was significantly increased in the patient subgroups compared with controls (17% versus 7%; P < 0.01), although the clinical significance of this association is unclear., Conclusion: This study of HLA associations in a diverse cohort of early synovitis patients emphasizes the complex degree of genetic interaction between alleles at several major histocompatibility complex loci, which regulates clinical phenotypes. In particular, SE and B27, while predisposing patients to characteristic clinical syndromes, had an unexpected degree of association in this cohort, perhaps explaining the overlap in clinical features in many patients.

Objective: The recent identification of antigens or nucleic acids of infectious agents in the joints of patients with reactive arthritis has raised questions about whether chlamydial or other infectious agent nucleic acids are also present in normal joints. We had the opportunity to study synovium from 30 asymptomatic volunteer subjects by use of polymerase chain reaction (PCR) for attempted identification of Chlamydia and other infectious agents., Methods: All subjects had blind needle synovial biopsies with the Parker-Pearson needle. DNA was extracted and PCR performed using primers for Chlamydia trachomatis, Chlamydia pneumoniae, Borrelia burgdorferi, and pan bacterial 16S ribosomal RNA (rRNA)., Results: Two subjects were identified with nucleic acid for the 16S rRNA gene of C trachomatis. All other PCR reactions were negative except for the pan bacterial 16S rRNA in the C trachomatis-positive subjects. Both subjects, although symptom free, had some evidence of synovial reaction., Conclusion: C trachomatis appears to occasionally be disseminated to joints without producing overt disease.

Two patients with diffuse cutaneous systemic sclerosis and spinal calcification, involving the lumbar spine in one and the cervical spine in the other, are described. Computed tomography-guided aspiration of the calcific masses was performed, and material aspirated from one patient was shown to be apatite, Ca5(PO4)3OH. One patient showed improvement following lumbar laminotomy, hemilaminectomy, and diskectomy.

Objective: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active psoriatic arthritis (PsA) resistant to nonsteroidal antiinflammatory drug therapy., Methods: Two hundred twenty-one patients with PsA were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on joint pain/ tenderness and swelling scores and physician and patient global assessments., Results: Longitudinal analysis revealed a trend favoring SSZ treatment (P = 0.13). At the end of treatment, response rates were 57.8% for SSZ compared with 44.6% for placebo (P = 0.05). The Westergren erythrocyte sedimentation rate declined more in the PsA patients taking SSZ than in those taking placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints, including dyspepsia, nausea, vomiting, and diarrhea., Conclusion: SSZ at a dosage of 2,000 mg/day is well tolerated and may be more effective than placebo in the treatment of patients with PsA.

Objective: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active ankylosing spondylitis (AS) that is not controlled with nonsteroidal antiinflammatory drug therapy., Methods: Two hundred sixty-four patients with AS were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on morning stiffness, back pain, and physician and patient global assessments., Results: While longitudinal analysis revealed a trend favoring SSZ in the middle of treatment, no difference was seen at the end of treatment. Response rates were 38.2% for SSZ and 36.1% for placebo (P = 0.73). The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). AS patients with associated peripheral arthritis showed improvement that favored SSZ (P = 0.02). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints., Conclusion: SSZ at a dosage of 2,000 mg/day does not seem to be more effective than placebo in the treatment of AS patients with chronic, longstanding disease. SSZ is well tolerated and may be more effective than placebo in the treatment of AS patients with peripheral joint involvement. This effect is more pronounced in treatment of the peripheral arthritis in this subgroup of AS patients.

Objective: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective in the treatment of reactive arthritis (ReA) that has been unresponsive to nonsteroidal antiinflammatory drug (NSAID) therapy., Methods: One hundred thirty-four patients with ReA who had failed to respond to NSAIDs were recruited from 19 clinics, randomized (double-blind) to receive either SSZ or placebo, and followed up for 36 weeks. The definition of treatment response was based on joint pain/tenderness and swelling scores and physician and patient global assessments., Results: Longitudinal analysis revealed improvement in the patients taking SSZ compared with those taking placebo, which appeared at 4 weeks and continued through the trial (P = 0.02). At the end of treatment, response rates were 62.3% for SSZ treatment compared with 47.7% for placebo treatment. The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints., Conclusion: SSZ at a dosage of 2,000 mg/day is well tolerated and effective in patients with chronically active ReA.

Objective: Difficulties in detecting Chlamydia trachomatis in human joints by polymerase chain reaction (PCR) may be related to whether synovial tissue or synovial fluid (SF) is used as the source of DNA in PCR amplification. In this study, a new PCR assay was developed and used to compare chlamydial DNA in paired samples of SF and synovial tissue from patients with arthritis., Methods: The PCR assay targeted the ribosomal RNA operons, which are present in 2 copies on the C trachomatis chromosome. DNA from several relevant bacteria and chlamydial serovars was used for testing this screening system. The detection of chlamydial DNA in nucleic acid preparations from matched samples of SF and synovial tissue was compared by PCR assay. Samples were obtained from 55 patients, including patients with reactive arthritis, Reiter's syndrome, and other arthropathies., Results: Testing of the PCR screening system confirmed it to be highly specific and sensitive. Use of this assay to screen DNA from SF and synovial tissue samples showed that 29 (53%) of 55 synovial tissue preparations were positive for chlamydial DNA, but only 16 (29%) of the matched SF samples from these 29 patients were similarly positive. Five (9%) of 55 SF samples, but not their tissue counterparts, were positive for chlamydial DNA by PCR., Conclusion: Detection of chlamydial DNA in the joints of patients by PCR gives positive results more often when synovial tissue rather than SF is the source of target nucleic acids. Although synovial tissue is the source of choice for the most reliable determination of chlamydia in the joint, both synovial tissue and SF should be assayed if possible.

Objective: To evaluate the utility of polymerase chain reaction (PCR) amplification in detecting DNA from venereal-associated microorganisms in the synovial fluid of patients with inflammatory arthritis., Methods: Oligonucleotide primers were developed for nested PCR based on Chlamydia, Ureaplasma, and Neisseria DNA sequences. PCR products were detected by gel electrophoresis and dot-blot hybridization. Primers specific for the target bacterial DNA were used to search for bacterial DNA in 61 synovial fluid specimens from patients with inflammatory arthritis, including several clinically associated with venereal infection., Results: Five of the 61 synovial fluid specimens were positive for Neisseria gonorrhoeae DNA. Four of the 5 patients had clinical diagnoses of gonococcal arthritis; the other patient had an unexplained monarthritis. One specimen from a patient with a clinical diagnosis of gonococcal arthritis was negative for N gonorrhoeae. Three of the 61 specimens were positive for Chlamydia DNA. Two were derived from patients with clinical diagnoses of reactive arthritis or Reiter's syndrome, and 1 was from a patient with unexplained monarthritis. One of the 61 specimens was positive from Ureaplasma DNA; this sample was from a patient with a clinical diagnosis of Reiter's syndrome. In an additional patient with Reiter's syndrome, Ureaplasma DNA was also found in prostate biopsy tissue and a urine sample obtained after prostate massage (synovial fluid not available)., Conclusion: These data support the classification of these 3 venereal-associated arthritides as infectious processes, and suggest that PCR for bacterial DNA is a useful method for detecting infectious agents in synovial fluid.

Objective: To investigate the biologic state of Chlamydia and its surface antigen expression in the synovial membranes of patients with Chlamydia-associated reactive arthritis/Reiter's syndrome (ReA/RS)., Methods: Expression of chlamydial lipopolysaccharide (LPS), major outer membrane protein (MOMP), and elementary body (EB) antigens was studied by gold labeling immunoelectron microscopy on 6 synovial membrane and 2 synovial fluid (SF) pellet samples from 6 patients with Chlamydia-associated arthritis. The study findings were compared with 24-hour cultures of HeLa cells infected with Chlamydia trachomatis EB., Results: Persistent C trachomatis infection was found in all 6 synovial membrane samples from patients who had either early or chronic arthritis. The infection persisted despite antibiotic treatment, including a 1-month course of doxycycline therapy. Most persistent organisms were atypical reticulate bodies (RBs) found in both fibroblasts and macrophages. Specific, but weak, immunogold staining for all 3 antibodies was found on both intracellular RBs and extracellular EBs. In the SF samples, Chlamydia surface antigens were detected only in phagosomes containing degraded electron-dense materials., Conclusion: The synovial membrane biopsies conducted in this study of Chlamydia-associated ReA/RS revealed atypical RBs with diminished MOMP and LPS expression. Such altered organisms may escape immune surveillance and contribute to disease chronicity; moreover, these organisms may be difficult to detect and treat in some ReA/RS patients.

A 57-year-old black man with sickle cell disease was admitted to the hospital because of a painful crisis. After a fall with a fracture into the right knee joint, he developed an acutely painful, swollen knee. Synovial fluid from the right knee showed leukocyte counts of up to 154,000/mm3 and was negative for urate and calcium pyrophosphate dihydrate crystals. Gram stains and cultures were negative. Some sickled red cells were seen by light microscopy; electron microscopy revealed crystal-like arrays of sickled hemoglobin tactoids in erythrocytes which were enfolded and phagocytized by the cells of the synovial fluid. We suggest that this phagocytosis of sickled red cells is the likely cause for the otherwise unexplained inflammation.

Objective: In this in vivo study, we investigated changes in the proteins that coat monosodium urate (MSU) crystals in human synovial fluid samples and rat air pouch fluid samples obtained sequentially during periods of active and resolving inflammation, in order to evaluate whether in vivo findings are consistent with hypotheses on roles of protein coating based on in vitro findings., Methods: Crystals from patients with gout were isolated from joint fluids with acute inflammation, and subsequently from the same joints at the time inflammation was resolving. Crystals were also obtained using the rat subcutaneous air pouch model. Immunogold was used to label proteins coating MSU crystals, for light microscopy (LM) and transmission electron microscopy (TEM) studies., Results: Dense immunogold-silver labeling for IgG was observed under LM on crystals from fluid with acute inflammation, whereas other proteins (apolipoproteins [Apo], fibronectin, fibrinogen, albumin) were not labeled significantly. Apo B became strongly positive on crystals as the inflammation subsided, whereas other proteins were only weakly positive and IgG became absent or weakly positive. Quantitative TEM evaluation confirmed the LM observations., Conclusion: This study provides the first in vivo evidence supporting the notion derived from previous in vitro studies that proteins coating MSU crystals change as inflammation evolves. Protein coatings may play an important role in the self-limited nature of gouty inflammation. IgG coating MSU crystals may enhance the inflammation. As the inflammation subsides, Apo B could displace the IgG by competitively coating sites on crystals and could contribute in part to the resolution of the acute gouty arthritis.

Objective: Reasons for apparent primary deposition of calcium pyrophosphate dihydrate (CPPD) crystals in some synovial membranes have not been systematically examined. We undertook the present study to investigate for and compare possible cellular and matrix factors related to the presence of these crystals in synovium and cartilage., Methods: Ten synovial membrane specimens and 6 cartilage specimens were obtained at the time of joint surgery from 10 patients with CPPD crystal deposition disease, for light microscopic (LM) and electron microscopic (EM) studies., Results: In all synovial and cartilage specimens, we found many of the small CPPD crystals aligned on or in parallel to collagen fibers, as seen by EM. In 9 of the 10 crystal-containing synovia, we found foci of chondrometaplasia adjacent to CPPD, by LM. In 7 of the synovia, including the one without LM evidence of chondrometaplasia, we observed the presence of chondrocyte-like cells by EM. We did not note any predictable relationship between the crystals and matrix vesicles, either in synovium or in cartilage., Conclusion: Our EM findings provide evidence of the relationship of small CPPD-like crystals, presumably early forms, to collagen fibers both in synovium and in cartilage. By LM and EM, we also demonstrate evidence of a close association between chondrometaplasia and CPPD deposits in synovium. We suggest that chondrometaplasia might be responsible for synovial CPPD formation in predisposed patients. Both the collagen fibers and chondrocyte-like cells seem to be involved in the primary formation of CPPD deposits in the synovium as well as in the cartilage.

Objective: There is much evidence indicating that chlamydial antigens in the synovium may be critical in the pathogenesis of Reiter's syndrome (RS), but it is not known whether intact organisms are present in that tissue in any stage of the disease. The present study was undertaken to begin to address this question., Methods: We used a highly specific and sensitive molecular hybridization screening system which detects chlamydial RNA, to examine synovial biopsy samples from 22 patients with various arthropathies, including 9 with RS., Results: Seven of the 9 RS patients were positive for chlamydial RNA, while 3 of the 13 non-RS patients were also positive; positive results in the non-RS patients probably indicate the actual presence of the organism, since these patients had arthritis that was otherwise incompletely explained., Conclusion: The detection of chlamydial RNA, in combination with previous findings of chlamydia-like particles and/or chlamydial antigens in the synovium of RS patients, suggests that whole bacterial cells are present in that tissue.

Objective: We report a hypogammaglobulinemic patient with a destructive oligoarticular arthritis, whose synovial fluid cultures were repeatedly sterile., Methods and Results: We identified a Ureaplasma urealyticum infection in his affected joints, using a polymerase chain reaction (PCR) assay., Conclusion: The PCR technique promises to be extremely valuable in the rapid and specific diagnosis of infectious arthritis.

A unique patient with type VIII Ehlers-Danlos syndrome and cutaneous vasculitis, resorptive osteolysis, and cardiac valvular disease is described. Collagen analyses identified morphologic and physical abnormalities of type I collagen. The patient's T lymphocytes could be propagated in vitro with type I collagen and produced a 60-kd lymphokine that bound this protein. Cellular autoimmunity to type I collagen may be responsible for this patient's intractable clinical condition.

We compared leukocyte populations in synovial fluid samples from 45 rheumatoid arthritis patients, grouped according to medications taken. Seventeen of the 22 patients receiving only nonsteroidal antiinflammatory drugs had lymphocytes as the single predominant cell. None of the 23 patients receiving second-line agents had lymphocyte predominance. These findings may have important implications for drug mechanisms and must be considered in future studies of synovial fluid.

We describe 3 children with Lowe's syndrome who developed joint manifestations--a previously rarely recognized feature. Two children had swelling and contractures of large and small joints; the third child had a small joint effusion and hypermobile joints. None of them had antinuclear antibody or rheumatoid factor; synovial effusions and biopsies showed no evidence of inflammatory cell infiltration. By light microscopy, profuse fibrous tissue and sparse synovial lining cells were found. Electron microscopy of the synovium of 2 patients showed large amounts of normal appearing collagen, unidentified thin fibrils, and focal profuse granular and fibrillar basement membrane-like material around small vessels, similar to findings described in other tissues in this syndrome. Whether these clinical and pathologic findings are results of the still incompletely understood basic metabolic defect or not, they should be recognized as features that may be seen in patients with Lowe's syndrome.

Acute lymphoblastic leukemia--hand mirror variant--was extensively restudied in a 22-year-old white female who survived for 22 months without therapy. Immune complexes to the baboon endogenous virus (BaEV) were found in the bone marrow plasma of the relapse specimen in 1977, but not in the bone marrow plasma from the terminal state in 1979. Immunoperoxidase-tagged IgM antibody prepared from the patient's bone marrow plasma revealed BaEV antigen on the tip of the uropod of the HMC at the time immune complexes were found in the marrow. Absence of immune complexes in the marrow. Absence of immune complexes in the bone marrow in the terminal state suggested a failure of the patient's immune surveillance system and/or possible immune suppression by chemotherapy.

To study the possible immunologic role of hand mirror lymphocytes (HML) in the control of Epstein-Barr virus (EBV)-infected B lymphocytes in patients with infectious mononucleosis (IM), we studied the in vitro interactions of these cells by time-lapse video light microscopy. Peripheral blood T lymphocytes isolated from three patients in the early recovery phase of IM were mixed with their autologous EBV-infected B cells. Motile lymphocytes with their characteristic hand mirror shape were observed to attach by their uropods to the B cells. The HML remained attached for variable periods ranging from 45-75 min. Following detachment, B cells that were in contact with HML underwent lysis. Mixtures of T cells from healthy donors and EBV-infected cell lines exhibited only rare uropod formation with no attachment or lysis of B cells. The present experiment indicates that contact-induced lysis of EBV-infected B lymphocytes is operative in IM and that this process is mediated by the HML.

Acute lymphoblastic leukemia was observed in a 22-year-old white female patient and was manifested by normal palelet counts, 50--60% hand mirror cells (HMC) in the bone marrow, and prolonged survival without treatment. The characteristic neoplastic cell had a nucleus within the "mirror" portion and a cytoplasmic uropod forming the "handle" portion. The presence of acid phosphatase and beta-glucuronidase activity suggested that the cell was a T cell lymphoblast. However, extensive immunologic surface marker studies indicated the cells were non-T, non-B. Terminal transferase activity further supported the lymphoid nature of the cell. The hand mirrow cells were considered a real phenomenon since they were demonstrated on phase contrast microscopy, scanning electron microscopy, and transmission electron microscopy. The cells did not grow in tissue culture and cytogenetics revealed a normal female karyotype. From the above observations, the HMC is a lymphoblast with morphological, cytochemical, and immunological features which may differentiate it from the usual cell in acute lymphoblastic leukemia. Therefore, cases involving increased numbers of hand mirror cells in the bone marrow and acute lymphoblastic leukemia require further investigation to elucidate the full importance of this cell. This study represents the first attempt to investigate this cell in detail.

Two patients with arthritis of the knee joints associated with cutaneous polyarteritis have been followed for 20 and 5 years. The arthritis is characterized by mild to moderate pain and stiffness and inflammatory joint effusions with predominantly polymorphonuclear leukocytes. Despite its chronicity, there has been no clinical or radiologic evidence of joint destruction. Necrotizing inflammation was seen in arteries of the deep skin but not in the small vessels observed in the synovial biopsy specimens.

A study was undertaken to determine if an intensive continuing medical education program in rheumatology could improve patient care. Fifteen primary care practitioners, who fit the description of educationally influential physicians, completed a 2-week academic medical center-based preceptorship. Improvement in physician knowledge, from a mean score of 65.3% to a mean of 82.9%, was documented using pre- and post-tests. Significant changes in physician behavior were documented using chart audits and patient interviews. The use of diagnostic tests and corticosteroids, and physician-patient interactions were the areas of greatest improvement. Functional outcomes for patients, measured by the Sickness Impact Profile, also improved. These findings suggest that a well-designed continuing medical education program can effect some changes in physician knowledge and behavior that will result in at least short-term improvement in patient outcomes.

A 48-year-old man with "rheumatoid arthritis" of 3 years duration was found to have synovial fluid lymphocytes that were maximally stimulated in vitro by chlamydial antigen, on 5 of 6 tests over 18 months. Immunocytochemical staining of a synovectomy specimen, using the peroxidase-antiperoxidase technique, subsequently revealed chlamydial antigen in the synovium. The possibility that Chlamydia in the synovium may produce features of rheumatoid arthritis is discussed.

One hundred and thirty-four initial bone marrows and 102 peripheral blood smears were evaluated for hand mirror cells (HMC) on pediatric patients with acute lymphoblastic leukemia (ALL). Twenty (15%) of the 134 patients were found to have greater than 5% HMC in their bone marrows. Only rarely were a few HMC noted in the peripheral blood. Survival did not appear to be related to the number of HMC in the bone marrow. Also, the median survival was not significantly greater in those HMC patients with greater than 40% HMC in their bone marrows when compared to the non-HMC group. From the available data in this study, it would appear that the number of HMC does not affect prognosis in the bone marrows of children with ALL. However, the prognostic significance of the HMC has not been clearly established in adults.

Although rheumatology manpower in United States medical schools has dramatically increased in the past decade, 13% of medical schools did not have a full-time staff rheumatologist in 1980. Thirty-eight percent of medical schools had 2 or less full-time rheumatologists. Staff rheumatologists and rheumatology fellows provided the majority of medical student education in the clinical aspects of rheumatic disease; however, rheumatologists in less than 50% of medical schools taught in the basic science curriculum or in related fields such as collagen biochemistry, metabolic bone disease, and orthopedic intervention in arthritis. The staff rheumatologists' time commitment to medical student education was inversely proportional to the rheumatology faculty size. At medical schools with no rheumatologists, however, there was little, if any, formal education in the rheumatic diseases. Most subjects are taught in systems-oriented lectures. Education is currently limited to the common rheumatic conditions such as bursitis and back pain. Only 62% of medical schools provide a structured course on the musculoskeletal examination. Elective rotations in rheumatology, usually offered in the third or fourth year, are currently being provided to only 15% of U.S. medical students.

Chrysotherapy was given to 14 patients with refractory psoriatic polyarthritis and to a comparable group of 42 patients with rheumatoid arthritis. The psoriatic patients had a higher rate of remission on gold and less severe toxicity than the rheumatoid arthritis patients. Psoriatic skin lesions were not affected by chrysotherapy.