tRNA-guanine transglycosylase from Escherichia coli: recognition of full-length ''queuine-cognate'' tRNAs

OBJECTIVE: To determine clinical variables useful in predicting the prognosis of patients with early rheumatoid arthritis (RA) by investigating the relationship between clinical variables and radiological progression. METHODS: One hundred eighteen patients with early RA whose symptoms developed within the previous year were enrolled in a prospective study. Data from the 98 patients who completed the 2 year study were analyzed, using the number of erosive joints and Larsen's score as the outcome of RA. RESULTS: Increases in the number of erosive joints at 12 months after entry into the study were significantly correlated with the number of swollen joints (r = 0.510), erythrocyte sedimentation rate (ESR) (r = 0.404), and C-reactive protein (CRP) (r = 0.487) at 6 months. The same results were seen using Larsen's score as the measure of outcome. The average number of erosive joints or mean Larsen's score at 12 months was higher in patients whose levels of CRP were high at 6 months and suppressed by 12 months, but increased much less in patients whose levels of CRP were successfully suppressed by 6 months. More joint erosions were noted in patients with positive rheumatoid factor (RF) than in RF negative patients. CONCLUSION: Joint erosions appeared with a certain time lag after active synovitis. Earlier introduction of effective treatment is recommended for the prevention of RA joint damage. The presence of RF, number of swollen joints, ESR, and levels of CRP at 6 months after starting therapy are the most useful variables to predict radiological progression in patients with early RA.     

Comparison of 3 quantitative measures of hand radiographs in patients with rheumatoid arthritis: Steinbrocker stage, Kaye modified Sharp score, and Larsen score

OBJECTIVE: To compare 3 quantitative hand radiograph scores, Steinbrocker stage, Larsen score, and Sharp score modified by Kaye, to one another and to other measures of clinical status in a cross sectional analysis of hand radiographs of 173 patients with rheumatoid arthritis (RA). METHODS: Radiographs were scored and compared to other measures of clinical status according to correlation and cross tabulation analyses. RESULTS: In these cross sectional studies, radiographic scores according to all 3 methods were correlated at high levels (r(s) > 0.5) with one another and duration of disease, as well as with scores for physical joint deformity and limited motion; at lower levels (0.3 < r(s) < 0.5) with physical joint swelling scores, functional status, and age; and at low levels of marginal or no clinical importance (r(s) < 0.3) with physical joint tenderness scores, laboratory data, and pain scores. CONCLUSION: The 3 scoring methods give similar quantitative information concerning hand radiographs of patients with RA. The Larsen and modified Sharp scores are preferred measures, as the detailed information facilitates comparison of different patients and monitoring of individual patients over time.     

Assessment of disease activity in rheumatoid arthritis using magnetic resonance imaging: quantification of pannus volume in the hands

We attempted to assess whether pannus volume measured by magnetic resonance imaging (MRI) can be used as an indicator of disease activity in rheumatoid arthritis (RA). Eleven women (mean age 46 yr) with uncontrolled RA were studied for 1 yr. Pannus formation in both hands was quantified using MRI at the start of the study, and at 6 and 12 months thereafter. The volume of enhancing pannus (VEP) was compared with changes in the radiological scores, grip strength, joint tenderness counts, joint swelling counts, erythrocyte sedimentation rate (ESR), and serum C-reactive protein (CRP). Patients were classified into three groups based on VEP changes between 0 and 12 months: unchanged (n = 2), decreased (n = 6) and increased (n = 3). VEP at 6 months and at 12 months differed significantly between the three groups. No statistically significant differences were found between the groups in radiographic scores, physical parameters or laboratory parameters despite the fact that some of these parameters changed in the direction indicated by the changes in VEP. VEP can be used as a new indicator to assess disease activity in individual RA patients and, using this parameter, treatment outcome can be assessed in fewer subjects than with traditional measures.     

Cyclosporine A in the treatment of early rheumatoid arthritis. A prospective, randomized 24-month study

OBJECTIVE: To investigate the efficacy, tolerability and safety of cyclosporine A (CSA) in early rheumatoid arthritis (RA) patients. METHODS: Patients with an early diagnosis of RA, a disease duration of less than 3 years, and without prior disease modifying antirheumatic drug (DMARD) treatment were studied. They randomly received oral CSA (3 mg/kg/day) or oral methotrexate (MTX) (0.15 mg/kg/week). In addition, all patients in both groups received oral prednisone (7.5 mg/day). RESULTS: Fifty-two patients were assigned to the CSA group and 51 to the MTX group. After 24 months of treatment, 48 patients from the CSA group and 48 from the MTX group showed significant clinical improvement. This was evaluated by the duration of morning stiffness, grip strength, the total joint count, joint swelling, and joint tenderness and pain, compared to pre-treatment values. The clinical improvement was also associated with a significant decrease in ESR and CRP values in both groups. No significant radiological deterioration was observed in the CSA patients compared to those treated with MTX after 24 months. Four patients from the CSA group dropped out of the study, two because of a synovitis flare, one because of severe hypertrichosis and one because of severe gingival hyperplasia. Three patients from the MTX group withdrew, one because of disease flare-up and two because of gastrointestinal disturbances. CONCLUSION: Early immunointervention in RA patients appears to be crucial to limit the development of joint damage. Cyclosporine A appears to be effective, well tolerated and safe in the long-term treatment of RA and can therefore be used as a first immunomodulatory drug in the armamentarium for the treatment of RA.     

Measuring health status in psoriatic arthritis: the Health Assessment Questionnaire and its modification

OBJECTIVE: The Health Assessment Questionnaire (HAQ) has proven to be a reliable and valid measure of outcome for a variety of arthritides. A recent modification of HAQ for spondyloarthropathy (HAQ-S) has also been reported. Our purpose was to evaluate the HAQ and HAQ-S as outcome measures in the assessment of patients with psoriatic arthritis (PsA). METHODS: The HAQ, including HAQ-S was administered to all patients attending our Psoriatic Arthritis Clinic between June and December, 1993. Clinical and radiological assessments were performed according to a standard protocol that measures disease activity, fibrositic tender points (TP), disease severity and damage. Analysis was performed using SAS for the PC. RESULTS: The patient population included 114 patients, 70 men and 44 women with a mean age of 49.3 years and a mean arthritis duration of 15.1 years. The mean HAQ score was 0.50, while the mean HAQ-S score was 0.53 (scores range 0 to 3 for this instrument). The overall HAQ and HAQ-S disability scores were highly correlated with several clinical measures of function, including grip strength (r = -0.63 and -0.59, respectively). American College of Rheumatology functional class (r = 0.59 and 0.60, respectively), as well as the number of fibrositic TP (r = 0.54 and 0.57, respectively). These disability scores also correlated highly with the overall number of actively inflamed joints (r = 0.49 and 0.50, respectively); however, they correlated only moderately or poorly with other measures of disease activity such as morning stiffness, total number of joint effusions, erythrocyte sedimentation rate (ESR) and the PASI score for psoriasis and with all measures of disease severity. A similar pattern of correlations was found between the individual subscales of the HAQ and HAQ-S and the clinical measures of function, activity, and severity, as well as between the pain scale and the various clinical measures. However, the correlations are generally lower. CONCLUSION: Our data suggest that HAQ and HAQ-S capture clinical measures of function and pain in PsA but do not correlate with disease severity. The HAQ and its modification for spondyloarthropathy may reflect fibromyaglia as a measure of pain and tenderness in these patients. Thus, the clinical assessment of disease activity and both clinical and radiological assessments of joint damage remain important outcome measures in PsA.     

Selective expression and functions of interleukin 18 receptor on T helper (Th) type 1 but not Th2 cells

OBJECTIVE: To evaluate tolerability and efficacy of combination therapy with methotrexate (MTX)/parenteral gold or MTX/other disease modifying antirheumatic drug (DMARD, d-penicillamine or chloroquine) in comparison with MTX monotherapy in patients with longstanding destructive active rheumatoid arthritis (RA). METHODS: In an open prospective trial all consecutive MTX-naive patients with active RA starting MTX treatment alone or in combination between January 1980 and December 1987, after failing one or more DMARD, were followed at regular intervals up to 108 months. Evaluations included the number of swollen joints (0-32), grip strength, patient assessment of pain and mobility, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and hemoglobin. Group 1, treated with MTX monotherapy (n = 97), was compared with Group 2, with combination therapy MTX/parenteral gold (n = 126) and Group 3 with MTX + other DMARD (n = 48). RESULTS: There were no significant differences between the groups in mean age (59/57/56 yrs), disease duration (9.6/7.7/8.3 yrs), seropositivity (80/88/82%), or ACR anatomical disease stage (2/3 in stage III and IV). The number of swollen joints (16.8/19.3/16.1 of 32) and the CRP (4.4/5.1/4.7 mg/dl) was significantly greater in Group 2; other disease activity variables were not significantly different. The mean MTX dose at baseline (mostly parenteral) was 16.8/17.0/12.8 mg and could be reduced to around 12 mg (predominantly oral) in the 3 groups. Frequency of adverse events (80/83/88%), nature of clinical (nausea, hair loss, stomatitis) and laboratory (liver enzyme elevation, slight proteinuria) side effects, and withdrawal rate for side effects (20.6/15.0/12.5%) were not significantly different between the groups. After 5 years 54/54/80% of patients continued their treatment. All efficacy variables improved significantly (p < 0.001) in all groups without significant intergroup difference. Improvement > 50% in the ESR was achieved in 63/68/41% and in the swollen joint count in 70/85/48% of patients after 3 years. The number of patients taking oral steroids decreased from 63/59/65% to 22/31/48% after 3 years. In half the patients hemoglobin increased by at least 1 g/dl. CONCLUSION: Combination therapy of MTX with parenteral gold or other DMARD is effective in reducing clinical and biochemical disease activity in patients with longstanding destructive RA with no greater risk of toxicity compared with MTX alone; our study however, did not show clear advantages of combination therapy versus monotherapy for effectiveness.     

Paradoxical response to valproic acid in a patient with a hypothalamic hamartoma

We investigated factors of daytime sleepiness in 22 middle-aged male patients with sleep apnea syndrome (SAS) using the Epworth sleepiness scale (ESS) and polysomnography. The subjects were classified into two groups according to ESS score as follows; low ESS group: ESS score < 10, and high ESS group; ESS score > or = 10. ESS score was significantly correlated with duration in which nocturnal oxygen saturation decreased below 90% (Time of SpO2 < 90%) (r = 0.54, p < 0.05). Time of SpO2 < 90% and percent of movement arousals at the termination of apnea/hypopnea (number of movement arousal/total number of apnea/hypopneas x 100) were significantly higher in high ESS group than in low ESS group. Our findings suggest that the severity of oxygen desaturation and sleep fragmentation caused by arousal response at the termination of apnea/hypopnea may be important factors of daytime sleepiness in patients with SAS.     

Indicators of work incapacity in the first year of chronic polyarthritis

Already in the early phase of rheumatoid arthritis (RA) sick-leave (SL) frequently indicates a severe handicap with respect to work capacity. However, the significance of demographic, disease and work characteristics for SL are not known in early RA. Therefore, the indicators of SL (defied as the history of SL as certified by a physician) were sought in a cross-sectional multicenter study of early RA (< or = 1 year duration). One-hundred-and-thirty-four employed consecutive outpatients fulfilled > or = 4 of 7 ARA 1987 criteria of RA: 85 females (63%), age 50 years (median), disease duration 7 months (median). At the time of the examination 74 of the 134 patients (55%) were on SL because of RA (dependent dichotomous variable of the analyses). In order to identify the most important indicators of SL all variables with p < or = 0.10 in univariate analyses were entered into a multivariate logistic regression (stepwise forward analysis, p < or = 0.10). Parameters included in two different regression models (somatic variable and depression, job characteristics, respectively) were analyzed together in order to find the final model (p < or = 0.05). The following variables were included in the final logistic regression model of SL (p < or = 0.05): higher values of age, pain, and number of swollen joints, frequent overhead work, frequent pressure of time at work. Other indicators of SL in univariate analyses (p < or = 0.10) were not included in the model: male sex, low functional capacity, walking time, control over the pace and activities of work, occupational qualification, elevated ESR and depression. Significant indicators of SL are work conditions, disease activity, pain and age. Thus interventions focusing on the amelioration of the work capacity and thereby on the reduction of SL should concentrate on both the control of the disease and the improvement of the work conditions.     

Long-term treatment of destructive rheumatoid arthritis with methotrexate

OBJECTIVE: To evaluate the tolerability and efficacy of methotrexate (MTX) treatment in patients with longstanding, progressive, active rheumatoid arthritis (RA) who had failed one or more disease modifying antirheumatic drugs (DMARD). METHODS: Two hundred seventy-one consecutive patients with RA in whom MTX treatment was introduced were followed at regular intervals for up to 108 months. Evaluations included the number of swollen joints, grip strength, patient assessment of pain and mobility, erythrocyte sedimentation rate (ESR), and hemoglobin. Radiographs of hands and feet were taken once a year and 32 joints were evaluated according to a modified Larsen score. RESULTS: Of the 271 patients, 269 had prior treatment with one DMARD, primarily parenteral gold, and 58% with 2 or more DMARD. MTX was started parenterally in all patients in doses between 15 and 25 mg weekly and continued by oral medication in most of the cases. Eighty-three percent of patients complained of adverse events. The most common side effects were nausea, hair loss, transaminase increase, and stomatitis. In 45 patients (16.5%), MTX was withdrawn because of side effects, mostly during the first year. Sixteen patients (5.9%) died during followup, mainly due to myocardial infarction, heart failure, stroke, or cancer. After one year, 78.7% and after 5 years 60.3% of the patients were still taking MTX. Number of swollen joints, ESR, grip strength, patient assessment of pain, and mobility improved significantly at all measurement points. Improvement in the swollen joint count and the ESR of over 50% was seen in more than 50% of patients. Inactivation of the disease, defined as < 2 swollen joints, ESR < 20 mm, and no concomitant steroid use, occurred in 8-14% of patients. Steroid intake was significantly reduced. In spite of clinical improvement the modified Larsen score showed a progression in the vast majority of patients. CONCLUSION: Even in patients with longstanding, active, destructive RA who failed one or more DMARD, MTX treatment is well tolerated and improves clinical and biochemical disease activity significantly, while radiographic progression is still present.     

Anti-collagenolytic mechanism of action of doxycycline treatment in rheumatoid arthritis

Tetracyclines exert, independently of their antimicrobial activity, anti-collagenolytic effects by inhibiting activities of human interstitial collagenases and by preventing the oxidative activation of latent pro-collagenases. We tested the clinical response to a 3-month doxycycline in concert with collagenase activity in 12 rheumatoid arthritis (RA) patients. Patients received 150 mg/day of doxycycline for 3 months. Clinical assessments at zero, six and 12 weeks comprised classification of the functional class, joint score index, Hb, CRP, ESR, health assessment questionnaire, visual analogue scale (VAS) of pain, pain disability index, comprehensible psychopathological rating scale (CPRS), SDS-PAGE laser densitometric collagenase activity measurements and Western blots. Significant reductions were seen in joint score index (P < 0.01), pain VAS (P < 0.05) and some CPRS parameters. Furthermore, collagenase activities measured from saliva by quantitative SDS-PAGE electrophoresis were significantly reduced during the 12-week intervention (P < 0.01). Western blots demonstrated intact 75-80 kDa enzyme protein (classic neutrophil collagenase), but also a newly discovered mesenchymal, less glycosylated 40-55 kDa MMP-8 subtype of fibroblast/chondrocytic origin. These results indicate that the documented favourable clinical response may in part be due to in vivo inhibition of classic neutrophil and mesenchymal collagenase/MMP-8 activities produced by doxycycline. This anti-collagenolytic doxycycline effects is mediated through inhibition of the enzyme activity and not through degradation of the enzyme, which may have contributed to the reportedly reduced tissue destruction, as has been seen in clinical studies concerning RA as well as reactive arthritis.     

Epidemiologic and actual importance of entero-hemorrhagic E. coli in Northern Bavaria (1996)

OBJECTIVES: To compare peripheral type 1 (T1) and type 2 (T2) T cell activities in rheumatoid arthritis (RA) patients with that found for osteoarthritic (OA) patients and healthy controls and to correlate peripheral T1/T2 cell activity in RA with parameters of the disease. METHODS: Peripheral blood mononuclear cells were isolated from patients with RA (n = 66), OA (n = 19), and healthy controls (n = 15). Primary T cell activity in these mononuclear cells was enhanced by means of anti-CD3/anti-CD28, which mimicks stimulation of T cells by activation of the T cell receptor and a major co-stimulatory signal. Interferon gamma (IFN gamma) production and interleukin 4 (IL4) production in the three groups were quantified as measures of T1 and T2 cell activity, respectively, and compared. Serum tumour necrosis factor alpha (TNF alpha), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and joint destruction assessed radiographically of RA patients were determined as parameters of disease activity and correlated with T1/T2 cell activity. RESULTS: Peripheral T cells from RA patients produced significantly less IFN gamma and more IL4 than T cells from both age and sex matched OA patients and healthy controls. Moreover, in RA patients both a decrease in IFN gamma and an increase in IL4 production correlated with an increase in serum TNF alpha, ESR, CRP, and joint destruction. CONCLUSIONS: These results suggest a role for differential T cell activity in RA. In view of the intra-articular T1 cell predominance the results might be explained by selective T1 cell migration into the joint or peripheral suppression of T1 cell activity.     

Radiographic outcome of recent-onset rheumatoid arthritis: a 19-year study of radiographic progression

OBJECTIVE: To describe the longitudinal radiographic course of rheumatoid arthritis (RA), and to identify and quantitate predictors of radiographic progression. METHODS: This prospective, longitudinal study of radiographic progression and clinical predictors of RA involved 256 patients with RA who were seen within the first 2 years of disease (mean 0.77 years) and were followed up for up to 19 years. Participants underwent a total of 6,278 clinical assessments (mean 24.5) and 934 paired radiographs (mean 3.1, range 2-6). Clinical assessments at every visit included determination of the erythrocyte sedimentation rate (ESR), grip strength, pain scores, tender joint counts, and anxiety and depression measurements. Regression analyses utilized time-integrated predictors. RESULTS: Overall, radiographic progression rates, as measured by the summary Sharp scores, appeared constant over the course of RA. The strongest correlate of progression was the time-integrated ESR (rho=0.53). This association grew stronger with time. At 0-5 years, 5-10 years, 10-15 years, and 15-20 years, correlations were 0.40, 0.50, 0.65, and 0.74, respectively, and for the period 10-20 years, the correlation was 0.67. In multivariate models, the mean ESR, mean grip strength, rheumatoid factor positivity, and tender joint count were independent predictors of radiographic progression. CONCLUSION: Radiographic damage occurs at a constant rate in RA, and is not greater early in RA or reduced later in the course of the illness. Acute-phase reactants are, by far, the strongest determinants of progression.     

Circulating levels of matrix metalloproteinases MMP-3 and MMP-1, tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP-1/TIMP-1 complex in rheumatic disease. Correlation with clinical activity of rheumatoid arthritis versus other surrogate markers

OBJECTIVE: To investigate whether plasma levels of matrix metalloproteinases 3 (MMP-3, stromelysin), MMP-1 (collagenase), tissue inhibitor of metalloproteinases 1 (TIMP-1), and MMP1/TIMP-1 complex (MT complex) are specifically elevated in erosive joint diseases compared to nonerosive rheumatic diseases, and to assess how these markers reflect the clinical activity of rheumatoid arthritis (RA) compared to circulating cytokines and markers of connective tissue turnover as well as established variables [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor titer]. METHODS: Plasma levels of MMP-3, MMP-1, TIMP- 1, and MT complex were determined by ELISA. One hundred fifteen patients with RA, 20 with osteoarthritis (OA), 28 with psoriasis arthritis (PsA), 24 with ankylosing spondylitis (AS), 3 groups with systemic autoimmune diseases, and 30 healthy controls were analyzed. In patients with RA routine laboratory variables, circulating inflammatory cytokines [interleukin 1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and IL-6], collagen degradation products, and markers of bone formation were determined in parallel and were correlated to 4 variables of clinical activity. RESULTS: MMP-3 levels were markedly elevated in RA compared to controls and OA, but also in all other groups, including 26 patients with systemic lupus erythematosus (SLE). MMP-1 levels were significantly elevated in RA, but also in OA, PsA, SLE, and mixed connective tissue disease. In contrast, MT complex was elevated in RA only. TIMP-1 was not different from controls. CRP levels, MMP-3, and ESR correlated best with clinical activity of RA. In contrast, there was no correlation of IL-1 and TNF-alpha and only a weak correlation of IL-6 with clinical measures. Among variables of connective tissue turnover, only pyridinoline and deoxypyridinoline crosslinks were weakly correlated with disease activity. CONCLUSION: Elevated MMP-3 and MMP-1 levels are not specific for RA or for erosive joint diseases in general. In contrast, elevated MT complex levels were observed in patients with RA. However, the correlation of MT-1 with clinical data was weaker than that of MMP-3. Elevated MMP-3 levels reflected disease activity of RA better than cytokine levels or markers of connective tissue turnover. However, MMP-3 levels do not exceed the association of CRP with clinical activity.     

A cross sectional assessment of health status instruments in patients with rheumatoid arthritis participating in a clinical trial. Minocycline in Rheumatoid Arthritis Trial Group

OBJECTIVE: To (1) validate the Short-Form Health Survey (SF-36) as a generic functional health status measure in patients with rheumatoid arthritis (RA); and (2) assess correlations between the SF-36 and other outcome measures used in the Minocycline in Rheumatoid Arthritis (MIRA) Trial. METHODS: We conducted a cross sectional analysis of the final visit outcome measures from the 48 week, multicenter, placebo controlled, double blind MIRA trial. Multitrait scaling analyses assessed convergent and discriminant validity and internal consistency reliability of the SF-36 in the study patients. Responses to comparable items on the SF-36 and modified Health Assessment Questionnaire (M-HAQ) regarding physical functioning were compared and questions from both instruments were also compared to other RA outcome measures. RESULTS: In patients with RA, the SF-36 had high internal consistency and reliability, high discriminant and high convergent validity. Moderate correlations were observed (r = -0.46 to -0.61, p < 0.01 in each case) for comparable items on the SF-36 and M-HAQ regarding dressing, walking, and bending. Joint tenderness score correlations with items on the M-HAQ and SF-36, and joint tenderness score correlations with the SF-36 scales were higher than for joint swelling scores. Physician and patient global assessments were most highly correlated (r = 0.58 and 0.66; p < 0.01, respectively) with the SF-36 bodily pain item. CONCLUSION: The SF-36 is a valid instrument for this RA population. The SF-36 correlates with the M-HAQ and the physician and patient global assessments. The usefulness of the SF-36 in measuring change in RA clinical trials requires testing in longitudinal studies.     

Gender differences in use of stress testing and coronary heart disease mortality: a population-based study in Olmsted County, Minnesota

The distribution of CD57+ T and CD56+ T cells in patients with RA was examined. In control osteoarthritis patients, these cells exist as a minor population in the peripheral blood. Our data show that in patients with RA, CD57+ T cell levels are elevated in peripheral blood, knee joint fluid, knee synovial membrane and bone marrow (BM), compared with peripheral blood of controls. CD57+ T cells are especially high in knee joint fluid and joint-adjacent BM, while CD56+ T cells show no such increase. CD57+ T cells contain a major population of CD8+ cells and higher proportions of CD4-8- cells and gammadelta T cells than do CD57- T cells. CD57+ T cells in peripheral blood and joint fluid increase with the duration of disease. Erythrocyte sedimentation rate (ESR) is inversely correlated with the proportion of CD57+ T cells in the joint fluid. Although RA frequently occurs in patients with CD3+57+ cell leukaemia, and some CD57+ T cells are likely to be involved in the onset of RA, we suggest that CD57+ T cells may rather suppress inflammation of RA, and other cellular components (e.g. granulocytes) may govern the severity of the inflammation of RA. These CD57+ T cells are probably generated extrathymically in the adjacent BM or joint space.     

A new approach to assessing rheumatoid arthritis (RA) disease activity using the American College of Rheumatology core set of disease activity measures for RA trials--a multi-center study

To characterize the American College of Rheumatology core set of disease activity measures for rheumatoid arthritis (RA) clinical trials (ACR core set measures) and the ACR definition of improvement of RA (ACR improvement definition), we studied 42 Japanese patients with active RA who were treated with DMARDs including mizoribine. Each patient's disease activity was assessed at the time of enrollment to the study and after 24 weeks using the ACR core set measures as well as the physical global assessment through the conventional measures. Twenty-five (60%) patients were discerned as showing improved by physicians through the conventional measures. This decision appeared to be based on improvement in Lansbury activity index (LAI) and C-reactive protein (CRP) value. Twelve of the 25 "improved" patients satisfied the ACR improvement definition. The 12 patients showed significant improvement in "outcome" measures including patients assessments of pain, disease activity, and physical function, compared to the 30 patients not satisfying the ACR definition. However, no significant differences were observed between these two groups in "process" measures including LAI, tender joint count, swallen joint count, or CRP value. In conclusion, the ACR core set measures including both process and outcome measures have potential to reflect clinical important changes on "real life" of patients with RA.     

Observations on the zinc protoporphyrin/heme ratio in whole blood

The aim of this study was to examine whether severity of preoperative pain intensity is related to postoperative pain and morphine consumption. Sixty consecutive patients scheduled for total hip surgery during intrathecal anesthesia were studied. Preoperative visual analog scale (VAS) scores and analgesic intake was assessed 1 day before surgery. Three groups of patients were identified: those with mild pain (n = 12, VAS score 0-4), moderate pain (n = 18, VAS score 4-7), and severe pain (n = 28, VAS score 7-10). Postoperative pain scores were recorded in the first 24 h, as was the amount of morphine delivered by the patient-controlled analgesia pump. There were no differences among the groups in VAS scores at any time. Severe preoperative pain levels correlated with significantly greater postoperative morphine intake. The mean morphine intake during the first 24 h postoperatively was 19.2 mg in the mild pain group, 21.2 mg in the moderate pain group, and 29.5 mg in the severe pain group (P < 0.05 compared with both other groups). We conclude that patients with severe preoperative pain self-medicate to achieve postoperative pain scores equivalent to those of patients with mild and moderate pain and require a greater postoperative morphine intake for adequate analgesia than patients with mild or moderate preoperative pain. IMPLICATIONS: In this study, we showed that severity of preoperative pain intensity relates to postoperative pain levels and morphine consumption. Patients scheduled for total hip surgery with severe preoperative pain require more postoperative morphine in the first 24 h.     

99mTc human immunoglobulin scintigraphy--a reliable method to detect joint activity in rheumatoid arthritis

The ability of 99mtechnetium labelled nonspecific, polyclonal human immunoglobulin G (99mTc-IgG) scintigraphy to depict and quantify synovial inflammation was studied in 30 patients with rheumatoid arthritis (RA). All patients were injected with 350 MBq 99mTc-IgG and imaging was performed 4 h later. This resulted in excellent images of inflamed synovium. Scores for 99mTc-IgG joint scintigraphy correlated highly with scores for joint swelling and C-reactive protein levels, weakly with pain scores and not with radiographic scores of joint destruction. These results suggest that 99mTc-IgG joint scintigraphy may provide an objective test to detect synovitis and measure the activity of the disease.     

The correlation of indium-111 joint scans with clinical synovitis in rheumatoid arthritis

OBJECTIVE: An inflammatory compartment radionuclide such as Indium-111 chloride (111InCl3) may offer advantages over bone seeking radionuclides in the assessment of active rheumatoid synovitis. As an iron analog, 111InCl3 binds iron complexing proteins including transferrin. Active rheumatoid synovitis is a transferrin receptor rich compartment, reflecting profound cellular activation and proliferation. We investigated 111InCl3 scanning for the detection of active rheumatoid arthritis (RA). METHODS: Nine patients satisfying ACR criteria for definite or probable RA were scanned twice at a 28-day interval. Patients were undergoing multiple medication changes with resultant fluctuating disease activity. Blinded readings were performed by an experienced nuclear medicine physician and correlated with simultaneous clinical examinations by a single rheumatologist. Sixteen assessed joint areas/patient and a total of 144 joint areas were available for analysis. RESULTS: Scintigraphy correlated with swollen and tender joint scores at both timepoints. Specificity was highest with stringent scoring. Sensitivity was lowest for small joints with lower 111InCl3 uptake relative to background. A receiver operator curve (ROC), generated to analyze the diagnostic value of varying 111InCl3 scan stringency, demonstrated utilization of the most accurate portion of the ROC curve by the reader. CONCLUSION: 111InCl3 joint scintigraphy correlates with clinically detectable rheumatoid synovitis, supporting the hypothesis that transferrin receptor levels reflect rheumatoid disease activity.     

Anti-ganglioside antibodies in patients with rheumatoid arthritis complicated by peripheral neuropathy

Gangliosides are a diverse class of glycolipids found in the plasma membrane of mammalian cells and are particularly abundant in cells of the nervous system. Serum antibodies to gangliosides have been detected in various neurological disorders with some evidence that they play a pathogenic role. In this study, we have investigated whether anti-ganglioside antibodies were elevated in a group of patients with rheumatoid arthritis (RA) who developed peripheral neuropathy (PN). An ELISA technique was used to test sera from 28 patients with RA and PN. 38 RA patients without PN and 20 normal controls for the presence of IgG and IgM anti-GM1 and sulphatide antibodies. The patients with RA and PN had higher pain scores (P < 0.005), more extra-articular features (P < 0.05), higher erosive scores (P < 0.0001), lower haemoglobin (P < 0.005), higher ESR (P < 0.001) and were more often on disease-modifying drugs (P < 0.05). Twelve RA patients with PN (43%), but only two RA controls (5%), had positive titres against one or more gangliosides (P < 0.001). The neurologic disability score (NDS) correlated with RA duration (P < 0.05), and with levels of IgM anti-GM1 (P < 0.001) and IgM anti-sulphatide (P < 0.05) antibodies. We conclude that PN is more common in patients with severe rheumatoid disease, and a significant proportion have elevated levels of anti-ganglioside antibodies.