Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
10606360 Celecoxib, a specific COX-2 inhibitor, has no significant effect on methotrexate pharmacok 1999 Dec OBJECTIVE: To determine the effects of celecoxib, a specific inhibitor of cyclooxygenase 2 (COX-2) on the renal clearance and plasma pharmacokinetic profile of stable methotrexate (MTX) doses in patients with rheumatoid arthritis (RA). METHODS: Fourteen adult female patients with RA taking a stable weekly dose of MTX (5 to 15 mg/wk) for a minimum of 3 months were randomized to receive concomitantly either celecoxib (200 mg BID) or placebo for a period of 7 days in a single blind, 2 period crossover study of MTX pharmacokinetics and renal clearance. RESULTS: The plasma pharmacokinetic profile of MTX did not change significantly when celecoxib or a placebo was coadministered. The mean renal clearance of MTX alone, 7.98+/-2.18 l/h, was virtually unchanged by coadministration of celecoxib (7.94+/-1.61 l/h) or placebo (7.97+/-1.19 l/h). CONCLUSION: Celecoxib has no significant effect on the pharmacokinetics or renal clearance of MTX in patients with RA, although these results should be confirmed in prospective studies of elderly and renally impaired patients.
10451825 The role of arthroscopy in wrist arthritis. 1999 Aug Recent advances in arthroscopic surgery techniques and instrumentation have enabled the surgeon to improve the treatment of wrist pathology. The arthroscopist can now perform a proximal row carpectomy or radial styloidectomy with minimal dissection and potentially less morbidity. The surgery requires a high level of skill from the surgeon. This is an area of medicine that is still evolving. Long-term studies are lacking but short-term results are promising. In the near future, the role of arthroscopy will better be defined as more research becomes available.
11758249 [Analysis of inflammation related gene expression spectrum in ankylosing spondylitis patie 2001 Sep 10 OBJECTIVE: To test the difference of gene expression patterns in peripheral blood mononuclear cells (PBMCs) among patients with ankylosing spondylitis (AS) or rheumatoid arthritis (RA) and healthy volunteers and to find potential discriminating genes. METHODS: The PBMC gene expression spectra of 7 patients with active AS, 6 patients with active RA, and 7 healthy volunteers were tested by microarray assay with 588 target gene filters. Semi-quantitative RT-PCR was performed to test the expression rates of thirteen inflammation related genes which had been with high expression rates in at least 4 arthritis patients by microarray assay, among 22 AS patients, 8 RA patients, and 7 healthy volunteers. RESULTS: The expression rates of inflammation related genes by cDNA microarray assay in healthy volunteer group, AS group, and RA group were 8.4%, 32.5% and 44.8% respectively (P < 0.001). The positive rate in RA patients was much higher than that in AS patients (P < 0.012). A significant increase of positive rate of these genes was also noticed in 2 active pulmonary tuberculosis patients. The expression rates of the 13 genes which were positive in at least 4 arthritis patients tested by semiquantitative RT-PCR in 22 AS patients, 8 RA patients and 7 healthy volunteers were very similar to those expression rates tested by cDNA microarray. CONCLUSION: The gene expression profiles of PBMC among AS patients are significantly abnormal and are significantly different from those among RA patients. The high expression of the 13 cytokines is not specific to AS.
11180899 Revision of failed metal-backed patellar component of Miller/Galante-I total knee prosthes 2000 Of 38 Miller/Galante-I total knee prostheses implanted between 1987 and 1990, 20 (53%) were revised. Failed metal-backed patella (15 knees; 40%) was the most frequent reason for revision. In most patients, the components were found well fixed to bone. The purpose of this study was to describe the revision technique we used for failed metal-backed patella. Total revision of all components would be ideal. However, removal of all components results in large bone loss, large blood loss, and a longer operation time. Because of the patients' relatively old age (78.7 years), less demanding activities of daily life (ADL), and the lower body weight of the Japanese patient, we chose a less invasive approach. The revision technique had the following features: (1) the grooved femoral component was not replaced, (2) the failed patellar component was replaced by an all-polyethylene patella, (3) synovectomy was performed, and (4) realignment of patellar tracking was done by lateral release and medial imbrication of the quadriceps mechanism. The mean follow-up after revision was 2 years, 4 months, and good short-term results were obtained. This less invasive approach would be beneficial for elderly patients whose ADL are less demanding.
10195644 GEECAT and GEEGOR: computer programs for the analysis of correlated categorical response d 1999 Jan GEECAT and GEEGOR are two user-friendly SAS macros for the analysis of clustered, correlated categorical response data. Both programs implement methodology which extend the generalized estimating equation (GEE) approach of Liang and Zeger (Biometrika 73 (1986) 13-22). GEECAT and GEEGOR both use a first set of estimating equations to model the marginal response. With GEECAT, either correlated nominal or ordered categorical response data can be analyzed. The program GEEGOR employs a second set of estimating equations to model the association of ordered categorical responses within a cluster using the global odds ratio as a measure of association. The programs run on both mainframe computers and microcomputers. Examples are provided to illustrate the features of both programs.
9852747 [Plain film and CT findings of pulmonary involvement in rheumatoid arthritis]. 1998 Oct OBJECTIVES: To analyze the plain film and CT findings of rheumatoid arthritis (RA)-associated lung diseases and to correlate them with clinical manifestations. METHODS/MATERIALS: We retrospectively reviewed the plain chest and CT findings of 51 RA patients with lung diseases. Sixteen CT findings were separately corded as present or absent, and drew up our classification of lung diseases as follows; 1. interstitial pneumonia/pulmonary fibrosis (IP/PF), 2. airway disease (AD), 3. parenchymal disease (PD), and 4. mixed. Four plain film findings were also recorded, and classified in IP/PF or AD group. This classification was analyzed with reference to clinical parameters and courses. RESULTS: Fifty-one patients were classified as follows; 1. IP/PF (n = 32, 62.6%), 2. AD (n = 15, 29.4%), 3. PD (n = 3, 5.9%), 4. mixed (n = 1, 2.0%). CT findings of PD were compatible with bronchiolitis obliterans organizing pneumonia with rapid improvement. IP/PF diagnosed with CT was depicted by the plain chest in 25 patients (78.1%). There is no false positive of the plain chest diagnosis in terms of IP/PF. As compared with IP/PF, AD consisted of significantly higher prevalence in female patients and patients with severe articular involvement and sinusitis. In spite of variable outcome in patients with AD, those with IP/PF showed the progression of honeycombing, and 4 of them were died from respiratory failure. CONCLUSIONS: CT based classification of rheumatoid lung diseases correlates with clinical manifestations and prognosis and is useful for clinical management in patients of RA. CT diagnosis is useful especially when plain chest does not demonstrate typical IP/PF pattern.
10627683 The use of magnetic resonance imaging in posterior tibial tendon dysfunction. 1999 Aug The role of magnetic resonance imaging in the evaluation of the patient with posterior tibial tendon dysfunction is discussed. Considerations for the proper positioning of the patient and optimal technique to obtain appropriate images of the posterior tibial tendon and associated joint abnormalities are highlighted. Cases are presented to show the effectiveness of magnetic resonance imaging in different clinical situations. The treatment algorithm for posterior tibial tendon dysfunction should include magnetic resonance imaging as a diagnostic tool when appropriate.
11899078 Molecular characterization of the T cell repertoire using immunoscope analysis and its pos 2001 Jul T lymphocytes play a central role in the pathogenesis of a large number of human conditions including autoimmunity and graft rejection. Although T cells are key players in mounting immune responses, the assessment of T cell repertoires has yet to find an important role in clinical decision making. In this review, we discuss the "immunoscope" technique and its potential diagnostic role in a variety of clinical scenarios. This is an RT-PCR based approach that subdivides a bulk T cell population (i. e. from blood, lymph, spleen, or tissue) into approximately 2800 groups based upon rearranged variable beta (Vbeta)/joining beta (Jbeta) gene segments and the resulting length of the T cell receptor's (TCR's) third complementarity determining region (CDR-3). This extensive subdivision, or focusing, allows clonal expansions to be directly observed. Such a fine-tuned analysis has revealed previously unappreciated aspects of the T cell repertoire. For instance, an antigen-specific immune response can be divided into both public and non-public components. The non-public repertoire contains the majority of the expanding T cells which are unique to the individual (private), or shared by only some (semi-private), while "public" T cells can be found responding to the antigenic determinant in every individual. Although they are often a minority of the response, the public T cell repertoire seems to play a more important role in defining, as well as driving, the overall immune phenotype in the animal. Immunoscope analysis has identified public and non-public responses in human pathologies, such as multiple sclerosis. The ability to characterize the driver T cells dictating the state of immunity/autoimmunity in individual patients will be an important step towards understanding autoimmunity and designing effective treatment for a variety of conditions including rheumatoid arthritis and multiple sclerosis. We review the current literature involving public and non-public repertoires and discuss the prospect that immunoscope analysis may play a central role in the study and perhaps the management of human autoimmune diseases, and cancer.
10941812 Serum creatine kinase in patients with rheumatic diseases. 2000 Serum creatine kinase (CK) activity is reduced in some conditions, including rheumatic diseases, but the aetiology and significance remain to be clarified. The aim of this study was to investigate relationships between serum CK activity and other muscle enzymes, muscle mass, renal function, steroid use and disease activity in patients with rheumatic diseases. Serum CK activity was measured in sera from 498 patients with rheumatic diseases: rheumatoid arthritis (RA, n = 145), systemic lupus erythematosus (SLE, n = 31), spondyloarthropathies (SpA, n = 35), polyarthralgia/arthritis (Poly, n = 74), miscellaneous group (MI, n = 46), and in non-inflammatory arthropathies (NIA, n = 167) as controls. Serum CK level was significantly reduced in RA (45.4 +/- 1.9 IU/l), SLE (46.4 +/- 4.2 IU/l), SpA (64.7 +/- 5.6 IU/l) and MI (63.4 +/- 4.8 IU/l), but not in poly (70.2 +/- 3.1 IU/l), compared to controls (78.9 +/- 2.4 IU/l) (P < 0.05). CK values correlated with aspartate aminotransferase (AST), erythrocyte sedimentation rate (ESR), body mass index (BMI) and platelets (Plat) in RA; ESR and haemoglobin (Hb) in SLE, AST, ESR and Hb in SpA; lactate dehydrogenase (LDH), AST, ESR and Hb in Poly; LDH, AST, ESR, Hb and Ccr in MI; and LDH, AST and ESR in controls. In all patients with rheumatic diseases CK level was significantly correlated with LDH, AST, alanine aminotransferase (ALT), ESR, C-reactive protein (CRP) and BMI and prednisolone dose, but not with Ccr, age and disease duration. In conclusion, our data support the possibility that reduced CK activity is inversely correlated with inflammatory activity and correlated with other muscle enzymes, muscle mass and steroid use, but not with renal function, age and disease duration in rheumatic diseases.
11592365 Epitope specificity of clonally expanded populations of CD8+ T cells found within the join 2001 Sep OBJECTIVE: To investigate the hypothesis that clonality of synovial T cells from patients with rheumatoid arthritis is at least partly due to the presence of virus-specific T cells expressing a restricted repertoire of T cell receptors (TCRs). METHODS: Using fluorescently labeled HLA class I-peptide tetramers, populations of virus-specific CD8+ T cells were identified in samples of peripheral blood and synovial fluid taken from 4 patients with inflammatory arthritis. The TCR repertoire of the virus-specific T cells in the synovial fluid was analyzed using a panel of TCR beta variable region-specific monoclonal antibodies. Where T cells expressing a particular Vbeta chain dominated the response to a viral epitope, the sequences of these Vbeta chains were derived from sorted populations of antigen-specific T cells by reverse transcription-polymerase chain reaction. RESULTS: CD8+ T cells specific for Epstein-Barr virus, cytomegalovirus, and influenza virus were enriched in synovial fluid compared with peripheral blood. Clonal or oligoclonal populations of CD8+ T cells were found to dominate the responses to these viral epitopes in synovial fluid. CONCLUSION: The results support the hypothesis that restricted T cell receptor usage by large populations of virus-specific T cells provides one explanation for the presence of clonally expanded CD8+ T cells within the joints of patients with inflammatory arthritis. Thus, T cell clonality at a site of inflammation may reflect enrichment for memory T cells specific for foreign antigens, rather than proliferation of autoreactive T cells specific for self antigens.
11466173 Patterns of drug consumption in relation with the pathologies of elderly Mexican subjects 2001 May PURPOSE: To describe the patterns of drugs consumed by the male and female elderly living in Mexican private and public nursing homes. METHODS: Three hundred and fifty elderly participants from four nursing homes (2 private and 2 public) were selected for the six month study: 108 subjects were excluded; the remaining 242 were between 65 and 100 years old; 123 were females and 119 males. A complete clinical history was taken and clinical files were reviewed. RESULTS: Of the 242 elderly studied, 193 took diverse medications and 28.5% were at risk of some type of drug interaction. The groups of drugs more frequently consumed were vitamins and anti-anemic medications, followed by cardiovascular drugs. Females consumed greater number of drugs. They also consumed more drugs simultaneously. CONCLUSIONS: There is a need to monitor the elderly for their drugs pattern use.
10812704 Cutaneous histiocytic lymphangitis: an unusual manifestation of rheumatoid arthritis. 2000 May Two cases are presented of unusual cutaneous lesions associated with rheumatoid arthritis in underlying joints. The lesions were evanescent, erythematous and violaceous partly macular and partly indurated plaques, with a livedo-like pattern of erythema at the edge in one case. Histological changes were identical in the two cases. The major features were dilated, dermal lymphatics containing aggregates of inflammatory cells, mainly histiocytes, with adjacent perivascular lymphoid aggregates. An appropriate name for this reaction would appear to be cutaneous histiocytic lymphangitis.
10888713 CD1 expression in psoriatic and rheumatoid arthritis. 2000 Jun OBJECTIVE: CD1 is a novel class of molecules which present non-protein antigens to T cells. The objective of this study was to evaluate the expression of CD1 in the skin and synovium of patients with psoriatic arthritis (PsA) in comparison with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Paired lesional skin (SK) and synovial membrane (SM) from four PsA patients, paired SK and SM from four RA patients, SM from eight RA and eight OA patients, and normal SK from four volunteers were studied using standard immunohistochemistry. RESULTS: In all PsA and RA skin samples CD1-positive cells were abundantly detected both in the dermis and in the epidermis. However, in the 24 SM examined CD1-positive cells were rarely found. In one patient only with RA, a few CD1a-positive cells were found in the SM. CD1b was scarcely expressed in the lining layer (LL) of five SM and in very few cells in the sublining layer (SL) of 11 SM. CD1c was rarely expressed in the LL of six SM and in very few cells in the SL of 13 SM. CONCLUSION: The paucity of CD1 in the PsA and RA synovium suggests that different subsets of antigen-presenting cells are involved in the pathogenesis of dermatitis and synovitis, respectively.
10755430 Estimation of the migration of tibial components in total knee arthroplasty. A roentgen st 2000 Mar Accurate quantitative measurements of micromovement immediately after operation would be a reliable indicator of the stability of an individual component. We have therefore developed a system for measuring micromovement of the tibial component using three non-contact displacement transducers attached to the tibial cortex during total knee arthroplasty (TKA). Using this system we measured the initial stability in 31 uncemented TKAs. All the tibial components were fixed by a stem and four screws. The initial stability was defined as the amount of displacement when a load of 20 kg was applied. The mean subsidence was 60.7 microm and the mean lift-off was 103.3 microm. We also studied the migration of the tibial component using roentgen stereophotogrammetric analysis (RSA) for up to two years after operation. Most migration occurred during the first six months, after which all prostheses remained stable. We defined migration as the maximum total point motion (MTPM) at two years after operation. The mean migration was 1.29 mm at two years. Our results show that there was a significant correlation between the initial stability and migration (p < 0.05) and emphasise the importance of the initial stability of the tibial component.
11136873 Raised pulmonary artery pressures measured with Doppler echocardiography in rheumatoid art 2000 Dec OBJECTIVE: To study the prevalence of echocardiographic abnormality and pulmonary hypertension in an unselected population of patients with rheumatoid arthritis (RA). METHOD: One hundred and forty-six RA patients, irrespective of cardiopulmonary symptoms, were assessed clinically and by echocardiography, including pulmonary artery pressure measurement, ECG, pulmonary function tests and high-resolution computed tomography scanning of the thorax. RESULTS: Two-dimensional echocardiography demonstrated significant cardiac disease in the form of reduced left ventricular ejection fraction (<64%) in 9% of patients, moderate mitral regurgitation in 4%, aortic stenosis in 4%, aortic regurgitation in 3% and Valsalva sinus rupture in 0.7%. In addition, 1% had detectable pericardial effusions. Thirty-one per cent of the RA patients had an estimated pulmonary artery systolic pressure of 30 mmHg or more, and 21% of all the RA patients had pulmonary hypertension without significant cardiac disease or lung disease evident on pulmonary function testing. CONCLUSIONS: A wide and frequent variety of echocardiographic cardiac abnormalities may be found in an unselected population of patients with RA. Using Doppler echocardiography, we have found pulmonary hypertension secondary to lung disease in 6% of the population and a larger than expected prevalence of mild primary pulmonary hypertension in patients with RA. The latter observation may be relevant to the high incidence of cardiovascular-related deaths observed in patients with RA
9603152 Airways involvement in rheumatoid arthritis: clinical, functional, and HRCT findings. 1998 May The aim of the present study was to assess the prevalence and characteristics of airways involvement in rheumatoid arthritis (RA) patients in the absence of interstitial lung disease. We prospectively evaluated, with high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs), 50 patients with RA (nine males and 41 females; mean age: 57.8 yr), including 39 nonsmokers and 11 smokers (mean cigarette consumption: 15.3 pack-yr) without radiographic evidence of RA-related lung changes. PFTs demonstrated airway obstruction (i.e., reduced FEV1/VC) in nine patients (18%) and small airways disease (SAD) (i.e., decreased FEF(25-75), defined as exceeding the predicted value by 1.64 residual SD [RSD] or more, and/or an increased phase III slope > 2 SD by single breath nitrogen washout) in four patients (8%). HRCT demonstrated bronchial and/or lung abnormalities in 35 cases (70%), consisting of air trapping (n = 16; 32%), cylindral bronchiectasis (n = 15; 30%), mild heterogeneity in lung attenuation (n = 10; 20%), and/or centrilobular areas of high attenuation (n = 3; 6%). Airway obstruction and SAD were correlated with the presence of bronchiectasis and bronchial-wall thickening (p = 0.003), and with bronchial infection (p = 0.01), but were unrelated to rheumatologic data. FEF(25-75) was reduced and the slope of phase III was increased in patients with airway changes on HRCT scans, whereas no PFT abnormalities were found in 13 of 15 patients with normal HRCT scans. HRCT depicted features of SAD in 20 of the 33 patients with normal PFTs. HRCT findings were unrelated to rheumatologic data. A high prevalence of airway abnormalities as assessed with HRCT and/or PFTs was observed in our RA population. HRCT appears to be more sensitive than PFTs for detecting small airways disease.
9101493 Variations and trends in the prescription of initial second line therapy for patients with 1997 Apr OBJECTIVE: To evaluate practice variation and time trends in the initial prescription of second line drugs for the treatment of rheumatoid arthritis (RA) by a group of selected rheumatologists. METHODS: We retrospectively reviewed medical charts of all patients with a diagnosis of RA, initially seen between January 1, 1985, and June 30, 1994, by rheumatologists from a tertiary center and a rheumatology referral clinic in Edmonton. RESULTS: 1427 patients initially seen between 1985 and 1994 were included in the study. Of these, 1244 (87%) received a second line drug, 71% within 1.5 years after the disease onset. Overall, antimalarials and parenteral gold were the most frequently prescribed. Statistically significant trends were observed for the years under study. From 1985 to 1987, the most frequently prescribed initial second line drug was parenteral gold, between 1988 to 1990, sulfasalazine, and after 1991, antimalarials. Methotrexate was rarely used as a first choice. Marked variability was observed among rheumatologists in the use of initial second line drugs. In general, year of prescription and prescribing rheumatologist were significantly associated with the selection of all second line drugs but methotrexate. In addition, disease duration and residence (urban or rural) were associated with the selection of antimalarials and parenteral gold. CONCLUSION: Most patients were treated early with second line drugs. Initial prescription patterns varied among rheumatologists. These patterns have changed over the last 10 years. An increasing trend in the use of antimalarials was noted, and unlike prescription patterns in the US, methotrexate was rarely used as the first second line drug.
11764344 Fixation of the Quatroloc femoral component: a biomechanical and clinical study. 2001 Dec The current study was designed to test the hypothesis that press-fit femoral components with proximal press-fit and distal mechanical interlock can achieve fixation sufficient to allow bone ingrowth in osteoporotic and in normal bone. The addition of steps along the tapered distal stem improved fixation in osteoporotic bone enough to reduce micromotion to less than 20 microm in response to physiologic axial and torsional load. The clinical portion of the study included 226 consecutive hips (223 patients) with 2- to 4-year clinical results after total hip arthroplasty with a rectangular femoral component using proximal porous coating and distal mechanical interlock. Patient age ranged from 36 to 92 years. At 2 years postoperative, 4% of the patients with Type A (normal) femoral bone, 3% with Type B (intermediate) bone, and no patients with Type C (osteoporotic) bone had thigh pain. No clinical cases of loosening have occurred in normal or osteoporotic femurs.
10813283 Rheumatoid arthritis in Sweden. Drug prescriptions, costs, and adverse drug reactions. 2000 May OBJECTIVE: Many patients with rheumatoid arthritis (RA) need continuous medication, bringing considerable costs for drugs and a need for monitoring adverse drug reactions. We studied drug exposure, drug costs, and adverse drug reactions in patients with RA in Sweden from 1987 to 1997. METHODS: Prescription patterns, drug costs, and adverse drug reactions, and their distributions and trends were analyzed by cross sectional annual data. Drug exposures and costs were assessed from the National Diagnosis and Therapy Survey. All costs were recalculated to the 1997 level using the drug price index. Information on adverse drug reactions was obtained from the national pharmacovigilance system. RESULTS: The drug prescription level was, on average, 2 defined daily doses (DDD) throughout the study period. Nonsteroidal antiinflammatory drugs (NSAID) accounted for > 40% of the drugs prescribed, methotrexate (MTX) 10%, corticosteroids 10%, and sulfasalazine 5%. Analgesics and opioids made up 14% of prescriptions - a low estimate considering the availability of over-the-counter preparations. Disease modifying antirheumatic drugs (DMARD) increased their proportion from 28.5 to 39.3%. Total costs were stable at $16 million US annually. NSAID costs decreased, while those of sulfasalazine, MTX, and cyclosporine increased. On average, 91 adverse drug reactions were reported annually. Hematological reactions (agranulocytosis, thrombocytopenia, leukopenia, pancytopenia) predominated, constituting 21% of reported reactions. Skin and gastrointestinal reactions, mainly mild, accounted for 15 and 14%, respectively. Deaths from adverse drug reactions were uncommon, about 3 per year, and were mainly attributed to hematological reactions. CONCLUSION: The total volume as well as the total cost of drug consumption for RA in Sweden was relatively constant during our 11 year observation period, despite a notable increase in the use of DMARD. This was mainly due to a decrease in costs per DDD of NSAID, and an increased use of cyclosporine. Drug related adverse reactions were dominated by hematological reactions, and fatal events were few. This emphasizes the need for an extended evaluation of which safety procedures are most cost effective for monitoring the drugs used for RA.
10369798 Effects of treatment of rheumatoid arthritis patients with an antibody against tumour necr 1999 Jul The therapeutic effects of a monoclonal antibody against tumour necrosis factor alpha (TNFalpha) were evaluated objectively in 10 patients with rheumatoid arthritis by 111In-labelled granulocyte imaging before and after treatment, and compared with changes in granulocyte kinetics with respect to the liver, spleen and lungs. Anti-TNFalpha resulted in a decrease in the size of the whole-body pool of marginating granulocytes, as reflected by a significant increase in the 30 min intravascular recovery of labelled granulocytes from 40% (S.D. 10) to 47% (S.D. 16) of injected activity (P<0.02). The 111In contents of the spleen, liver and lungs were unchanged, so the origin of the increment in recovery was presumed to be a reduction in granulocyte margination in inflamed synovium, although this was not quantifiable. The sizes of the granulocyte pools in the liver and lungs, expressed as the 111In content of the organ per unit of circulating 111In-labelled cells, were not significantly different after treatment, but the splenic granulocyte pool decreased by 16% (S.D. 19) (P<0.05). Individual changes in the size of the splenic pool showed no significant correlation with corresponding changes in 30 min recovery or with corresponding indices of inflammation (24 h 111In-granulocyte joint activity and C-reactive protein). We conclude that anti-TNFalpha produces an obvious resolution in inflammatory joint activity that is accompanied by an increased circulating component of the total blood granulocyte pool, as a result of decreased margination at sites of inflammation. Anti-TNFalpha may also produce a specific decrease in splenic granulocyte pooling, independent of any anti-inflammatory effects, although a similar decrease in the lungs, which might be anticipated as a result of reduced cytokine-induced granulocyte activation, could not be detected.