Cost of Finnish statutory inpatient rehabilitation and its impact on functional and work capacity of patients with early rheumatoid arthritis: experience from the FIN-RACo trial.

OBJECTIVE: To explore the cost of the statutory inpatient rehabilitation system in Finland and its impact on the functional and work capacity of patients with early rheumatoid arthritis (RA). METHODS: In the Finnish Rheumatoid Arthritis Combination-Therapy trial (FIN-RACo), 195 patients with recent-onset RA, 162 of them available for the work force, were randomly assigned to two different drug treatment strategies for 2 years. Otherwise, the patients received routine multidisciplinary care and, if their functional or work capacity was endangered, were referred to inpatient rehabilitation. After a 5-year follow-up, data on rehabilitation, sick leave, and RA-related disability pensions were obtained from official registers. RESULTS: Of the 162 patients, 49 (30%) underwent inpatient rehabilitation at an average cost of EURO5400. The rehabilitated patients more often worked in white-collar jobs and had more pain and a worse Health Assessment Questionnaire (HAQ) score (1.0 vs. 0.78; p = 0.01) at baseline. Their HAQ scores remained higher throughout follow-up (p<0.001); no change appeared over inpatient periods [mean 0.01; 95% confidence interval (CI) -0.13 to 0.16]. No independent impact of rehabilitation on the HAQ score emerged in an adjusted generalized estimating equations (GEE) model (p = 0.55). Nor did any improvement in work capacity appear: average lost productivity (human capital approach) per patient-year was EURO10 155 (95% CI 6994-14 196) before and EUR 12 839 (95% CI 8589-19 139) after the start of rehabilitation. CONCLUSION: For patients with recent-onset RA, the Finnish statutory inpatient rehabilitation system had no positive impact on either functional or work capacity during the first few years, despite its considerable cost.

Indoleamine 2,3-dioxygenase activity is increased in patients with systemic lupus erythematosus and predicts disease activation in the sunny season.

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme which suppresses T lymphocyte activity. IDO activity can be determined by relating kynurenine, the main metabolite of tryptophan, to tryptophan (kyn/trp). We have demonstrated recently that systemic lupus erythematosus (SLE) is activated during the sunny season as measured by the European Consensus Lupus Activity Measurement Index (ECLAM) activity score. Our aim here was to establish whether IDO-dependent mechanisms are involved in the activation process of SLE. Kyn/trp was measured by reverse-phase high-performance liquid chromatography (HPLC) in 33 (30 female, three male) SLE patients in winter, spring and summer and in 309 healthy control subjects. At the same time-points the SLE patients were examined by a rheumatologist and a dermatologist and the activity of SLE assessed by the ECLAM score. IDO activity was higher in SLE patients than in healthy subjects. There was no seasonal variation in IDO activity in SLE patients and it did not correlate with the ECLAM activity score in winter. However, there was a significant correlation between IDO activity and the ECLAM score both in spring and in summer. High IDO activity in winter predicted subsequent activation of SLE in spring and summer. Our results indicate that IDO-dependent immunosuppressive mechanisms are activated in SLE patients. Exposure to sunlight or another factor causing seasonal variation in SLE activity leads to insufficiency of this suppression in a subgroup of patients, causing activation of SLE. High IDO activity in winter predicts activation of SLE in the sunny season.

Predictors of productivity loss in early rheumatoid arthritis: a 5 year follow up study.

OBJECTIVE: To explore baseline risk factors for productivity loss and work disability over 5 years in patients with early, active RA. PATIENTS AND METHODS: In the FIN-RACo trial, 195 patients with recent onset RA were randomised to receive either a combination of DMARDs with prednisolone or a single DMARD for 2 years. At baseline, 162 patients were working or available for work. After 5 years' follow up, data on sick leave and retirement were obtained from social insurance registers or case records. The cumulative duration of sick leaves and RA related disability pensions was counted for each patient. To analyse predictors of productivity loss, the patients were divided into four groups according to duration of work disability per patient year. RESULTS: Patient's and physician's global assessment of RA severity > or =50 and HAQ score > or =1.0 were risk factors for extension of productivity loss (OR (95% (CI) 1.77 (1.00 to 3.16), 1.85 (1.03 to 3.32), and 1.78 (1.01 to 3.14), respectively). Additional risk factors were low education level (2.40 (1.18 to 4.88)) and older age (1.03 (1.00 to 1.06)); combination treatment was a protective factor (0.59 (0.35 to 0.99)). CONCLUSION: At baseline, the risk of future productivity loss is best predicted by education level, age, global assessments of RA severity, and HAQ score.

HLA-DR-DQ haplotypes and genotypes in Finnish patients with rheumatoid arthritis.

OBJECTIVES: To elucidate the contribution of HLA-DR-DQ haplotypes and their genotypic combinations to susceptibility to rheumatoid arthritis, and to evaluate the various models for HLA associated risk for the disease in a series of Finnish patients. METHODS: 322 Finnish patients with rheumatoid arthritis were typed for common north European HLA-DR-DQ haplotypes and compared with a series of 1244 artificial family based control haplotypes. RESULTS: The association of the so called shared epitope (SE) haplotypes (DRB1*0401, *0404, *0408, and *01) with rheumatoid arthritis was confirmed. The DRB1*0401 haplotypes carried a far stronger risk for the disease than the (DRB1*01/10)-(DQA1*01)-DQB1*0501 haplotypes. Seven protective HLA haplotypes--(DRB1*15)-(DQA1*01)-DQB1*0602; (DRB1*08)-(DQA1*04)-DQB1*04; (DRB1*11/12)-DQA1*05-DQB1*0301; (DRB1*1301)-(DQA1*01)-DQB1*0603; (DRB1*1302)-(DQA1*01)-DQB1*0604; (DRB1*07)-DQA1*0201-DQB1*0303; and (DRB1*16)- (DQA1*01)-DQB1*0502--were identified. In accordance with the reshaped shared epitope hypothesis, all the protective DRB1 alleles in these haplotypes share either isoleucine at position 67 or aspartic acid at position 70 in their third hypervariable region motif. However, differences in the disease risk of haplotypes carrying the same DR but different DQ alleles were also found: (DRB1*07)-DQA1*0201-DQB1*0303 was protective, while (DRB1*07)-DQA1*0201-DQB1*02 was neutral. The same haplotypes carried different risks for rheumatoid arthritis depending on their combination in genotypes. CONCLUSIONS: When assessing the influence of HLA genes on the susceptibility to rheumatoid arthritis, not only should the HLA-DR or -DQ alleles or haplotypes be unravelled but also the genotype. The effect of HLA class II region genes is more complicated than any of the existing hypotheses can explain.

Seasonal variation of disease activity of systemic lupus erythematosus in Finland: a 1 year follow up study.

OBJECTIVES: To study the role of different seasons in the disease activity of patients with systemic lupus erythematosus (SLE). Additionally, to evaluate whether the outdoor behaviour during the summer or a photoprovocation test affects disease activity. METHODS: 33 patients with SLE were examined by a rheumatologist and a dermatologist at a university hospital in winter, spring, and summer. The activity of SLE was assessed by the ECLAM index. Their outdoor behaviour was recorded by a questionnaire during the summer. In the winter, 12 patients were photoprovoked by ultraviolet A and B radiation on a small skin area. RESULTS: The ECLAM scores were higher in spring and tended to be higher in summer than in winter (p = 0.006 and p = 0.051). This finding, as well as the outdoor behaviour, were independent of the patients' own impression of their photosensitivity. Overall, the sun protection actions were inadequate. The photoprovocation had no statistical effect on disease activity, but one patient had a violent exacerbation of SLE manifestations shortly after the photoprovocation. CONCLUSIONS: In the northern climate SLE may be activated during the sunny season. Therefore, more effort should be focused on sun protection of patients with SLE.

Effect of a three month course of ciprofloxacin on the late prognosis of reactive arthritis.

BACKGROUND: The value of antibiotics in the treatment of reactive arthritis (ReA) is still controversial. OBJECTIVES: To analyse the long term outcome of patients with ReA, treated with a three month course of ciprofloxacin or placebo. METHODS: Patients who had had ReA and had participated in a double blind, placebo controlled trial on the effectiveness of ciprofloxacin 4-7 years earlier were invited to a clinical examination. Of the 71 patients who were included in the original study, 53 agreed to visit the clinic for an examination. Twenty six of 53 patients had originally received ciprofloxacin and 27 had belonged to the placebo group. Of these, 20 in the ciprofloxacin and 25 in the placebo group were HLA-B27 positive. RESULTS: 11/27 (41%) patients in the original placebo group had now developed chronic rheumatic disease, as compared with only 2/26 (8%) patients originally treated with ciprofloxacin (p=0.006). Two patients who originally had received placebo, none in the ciprofloxacin group had developed ankylosing spondylitis, and three patients in the original placebo group, none in the ciprofloxacin group had recurrent anterior uveitis. The same tendency was seen when several different measures were analysed. Of the patients with chronic spondyloarthropathy, 10 in the placebo and none in the ciprofloxacin group were HLA-B27 positive. CONCLUSION: Analysis 4-7 years after the initial ReA suggests that a three month course of antibiotics in the acute phase may have a beneficial effect on the long term prognosis.

Mononuclear cell response to enterobacteria and Gram-positive cell walls of normal intestinal microbiota in early rheumatoid arthritis and other inflammatory arthritides.

OBJECTIVE: To study whether enterobacteria and Gram-positive bacterial cell walls (BCW) derivedfrom normal intestinal microbiota are involved in the etiopathogenesis of early rheumatoid arthritis (RA). METHODS: Peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) were isolatedfrom patients with early RA (the average duration of 5 months) and the controls (other types of inflammatory arthritis). The mononuclear cell proliferation and tumor necrosis factor-alpha (TNF-alpha) responses to heat-killed Salmonella enteritidis (SE). Yersinia enterocolitica (YE), and Escherichia coli (EC), and to Gram-positive BCW derived from four common intestinal indigenous bacteria, Eubacterium aerofaciens (EA), Eubacterium limosum (EL), Lactobacillus casei (LC), and Lactobacillus fermentum (LF), and a BCW derived from a pathogen, Streptococcus pyogenes (SP) were investigated. RESULTS: 39% or 56% of patients with early RA showed significant proliferation responses by PBMC or SFMC against enterobacteria, respectively. In other types of arthritis, corresponding figures were 59% or 66%. When BCW were used as antigens, 8.1% or 23% of patients with early RA showed proliferation responses by PBMC or SFMC, respectively. In other types of arthritis the corresponding figures were 7.5% or 35%, respectively. However, TNF-alpha production by SFMC stimulated by EA BCW, SE, YE or EC, was significantly higher in early RA than in other types of arthritis. CONCLUSION: These results suggest that SFMC reacting with enterobacteria or BCW exist in some patients with early RA, but also in other types of inflammatory arthritis. Intestinal bacterial agents may play a role in the etiopathogenesis of RA, but the effect appears to be non-specific.

Differences between female and male patients with familial rheumatoid arthritis.

OBJECTIVE: To determine whether there are genetic differences between female and male patients with familial rheumatoid arthritis (RA). METHODS: 45 men and 119 women from 78 families with RA who all had at least one first degree relative with RA were compared. HLA-DRB1 alleles were analysed, including DRB1*04 subtypes and associations of DRB1*04 haplotypes with DQB1*0301 or DQB1*0302 alleles, the age of the patients at disease onset, the presence of rheumatoid factor (RF), joint erosions, and rheumatoid nodules. RESULTS: HLA-DRB1*13 allele (the subtype allele of DR6, reported to be protective against the development of RA) was found in 14/119 (12%) of female but in none of the male patients (p=0.036). The HLA-DR4 allele was found slightly more often in men than women patients with familial RA (31/45 (69%) v 75/119 (63%), NS). Men were also more often RF positive than women (44/45 (98%) v 98/117 (84%); p=0.031). On the other hand, the mean age at onset of RA was significantly lower in the female group (40.4 years) than in men (46.6 years, p=0.0044). CONCLUSION: The results indicate that there is stronger genetic background in familial male than female patients with RA in the genetic susceptibility defined by the studied HLA antigens. However, the earlier age of onset of the disease in female group and the increased proportion of women with RA indicate that there are additional sex related predisposing factors enhanced in familial cases.

Effect of a three month course of ciprofloxacin on the outcome of reactive arthritis.

BACKGROUND: Treatment of reactive arthritis (ReA) with antibiotics has so far remained controversial. Eradication of the causative microbe appears logical, but short term antibiotic treatment has no beneficial effect on the outcome of ReA. OBJECTIVE: To evaluate the effect of a three month course of ciprofloxacin on ReA. METHODS: In a randomised, double blind, placebo controlled trial, between December 1992 and February 1996, 71 patients with acute ReA triggered by a gastrointestinal or a urogenital infection were randomly assigned to receive ciprofloxacin 500 mg or placebo twice daily for three months. Patients were assessed at study entry, at 6 weeks, 3 months, 6 months, and 12 months. Sixty two patients were valid for the efficacy analysis. The primary outcome measures were erythrocyte sedimentation rate, number of swollen joints, patients self assessment, and complete recovery. RESULTS: Adverse events were mostly mild and occurred in both treatment groups. There were no statistically significant differences in any of the primary or secondary efficacy variables between the study groups at baseline or during the 12 month follow up. All primary outcome measures indicated that the condition of the patients improved during the study. CONCLUSION: Both groups tended to recover. Ciprofloxacin, given as a three month course, had no advantage over placebo treatment.

Immunogenetic differences between patients with familial and non-familial rheumatoid arthritis.

OBJECTIVE: To search for possible immunogenetic differencies between the patients with familial and non-familial rheumatoid arthritis (RA). METHODS: The study compared 129 familial RA patients with 217 non-familial patients for the frequencies of HLA-DR antigens including DR4 subtypes, DR4-DQB1*0301 and DR4-DQB1*0302 haplotypes and HLA-B27 antigen as well as the age of disease onset and existence of rheumatoid factor or joint erosions. RESULTS: Two major differences between familial and non-familial groups were found: firstly, familial RA patients had increased frequency of HLA-DR4 as compared with the non-familial RA group (68.2 v. 54.8%; p = 0.019). Secondly, the mean age at onset of RA was significantly lower in the familial than in the sporadic RA patients (42.0 v. 46.5 years; p = 0.0020) and the difference still remained when the DR4 positive and negative subgroups were compared separately. CONCLUSION: These results confirm the more prominent association with HLA-DR4 in familial than in the non-familial cases and suggest that accumulation of HLA risk genes may, at least partly, explain the familial occurrence of the disease. Other susceptibility genes may also be concentrated in multiplex case families as suggested by an earlier age at the onset of RA in both HLA-DR4 positive and negative familial patients.

Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group.

BACKGROUND: The treatment of rheumatoid arthritis should aim at clinical remission. This multicentre, randomised trial with 2-year follow-up sought evidence on the efficacy and tolerability of combination therapy (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) compared with treatment with a single disease-modifying antirheumatic drug, with or without prednisolone, in the treatment of early rheumatoid arthritis. METHODS: 199 patients were randomly assigned to two treatment groups. 195 started the treatment (97 received combination and 98 single drug therapy). Single-drug therapy in all patients started with sulphasalazine; in 51 patients methotrexate was later substituted. Oral prednisolone was required by 63 patients. The primary outcome measure was induction of remission. Analyses were intention to treat. FINDINGS: 87 patients in the combination group and 91 in the single-therapy group completed the trial. After a year, remission was achieved in 24 of 97 patients with combination therapy, and 11 of 98 with single-drug therapy (p=0.011). The remission frequencies at 2 years were 36 of 97 and 18 of 98 (p=0.003). Clinical improvement (American College of Rheumatology criteria of 50% clinical response) was achieved after 1 year in 68 (75%) patients with combination therapy, and in 56 (60%) using single-drug therapy (p=0.028), while at the 2-year visit 69 and 57 respectively (71% vs 58%, p=0.058) had clinically improved. The frequencies of adverse events were similar in both treatment groups. INTERPRETATION: Combination therapy was better and not more hazardous than single treatment in induction of remission in early rheumatoid arthritis. The combination strategy as an initial therapy seems to increase the efficacy of the treatment in at least a proportion of patients with early rheumatoid arthritis.

Tumour necrosis factor microsatellites in reactive arthritis.

The purpose was to study tumour necrosis factor (TNF)-a, -b and -c microsatellites as potential new susceptibility markers for reactive arthritis (ReA). Fifty-nine patients typed for HLA-B27 were studied for frequencies of TNF microsatellite alleles and compared with allele frequencies determined from 285 random haplotypes and 46 healthy HLA-B27-positive controls. TNFa, -b and -c microsatellite sequences were amplified by the polymerase chain reaction, and the size of the product was defined by an automated sequencer. The frequencies of TNFa6 and -c1 alleles were found to be increased in patients with ReA, whereas TNFa11 and -c2 frequencies were decreased as compared to control haplotypes. The increase in the c1 allele in patients with ReA independently from HLA-B27 suggests that it might be a new susceptibility marker for the disease. The association of ReA with other alleles was due to a linkage disequilibrium with HLA-B27.

TAP2 alleles in inflammatory arthritis.

Sixty patients with reactive arthritis (ReA) and 40 with rheumatoid arthritis (RA), were typed for H LA-B27 and class II antigens DR and DQ, and studied for TAP2 gene polymorphism in comparison with 60 healthy controls. TAP2 polymorphisms at positions 379, 565, 665, and 687 were analyzed using amplification refractory system-based PCR and polymorphisms at positions 386 and 651 using oligonucleotide hybridization. The frequency of the TAP2A/A genotype was 30%(12/40) in RA, in contrast to 13% (8/60) in the controls. This genotype was further associated with DRB1*04 positive RA (10/24, 42%, P=0.01), as well as the TAP2A allele (31/48, 65%, P =0.012). Thr/Thr dimorphism at TAP2 position 665 (24/40, 60%, P=0.024) and Stop/Stop dimorphism at TAP2 position 687 (24/40, 60%, P=0.024) were found to be increased in RA patients as compared to controls. When TAP2I/J polymorphism was studied, TAP2J positivity was found associated with the HLA-B27DR4-DQB1*0301-haplotype in ReA patients. 9/12 of these were positive as compared to 20/60 in random controls (P=0.010). Polymorphisms of the TAP2 gene were found to be associated with subgroups of RA and ReA patients with disease associated markers (e.g. TAP2A in DRB1*04 positive RA, or TAP2J in HLA-B27-DRB1*04-DQB1*0301 positive ReA). These may thus serve as additional markers of specific haplotypes associated with susceptibility to inflammatory arthritis.

A randomized, double-blind, placebo-controlled study of moclobemide and amitriptyline in the treatment of fibromyalgia in females without psychiatric disorder.

OBJECTIVE: To study the usefulness of moclobemide and amitriptyline in the treatment of fibromyalgia (FM) in females without psychiatric disorder. METHODS: In the present four centre, 12 week study, 130 female FM patients not suffering from psychiatric disorders were randomized to receive amitriptyline (AMI; 25 37.5 mg), moclobemide (MOCLO; 450-600 mg) or identical placebo. RESULTS: Seventy-four, 54 and 49 per cent of patients on AMI, MOCLO and placebo, respectively, were judged as responders. The patients on AMI also managed best regarding the respective improvements during the trial in general health, pain, sleep quality and quantity, and fatigue on visual analogue scales (VAS), the areas of the Nottingham Health Profile (NHP), as well as in the three Sheehan's functional disability scales. In the within-group comparisons, MOCLO also improved pain assessed both on VAS and on the NHP pain dimension, but the improvement was invalidated by the poor success of the drug with regard to sleep. The tolerabilities of all three drugs were comparable. CONCLUSION: The study indicates that MOCLO may not be helpful in FM patients free from clinically meaningful psychiatric problems.

Detection of rubella, mumps, and measles virus genomic RNA in cells from synovial fluid and peripheral blood in early rheumatoid arthritis.

OBJECTIVE: To determine, by studying patients with early rheumatoid arthritis (RA), whether rubella virus (rubella), mumps virus (mumps), or measles virus (measles) plays a role in the pathogenesis of RA. METHODS: Polymerase chain reaction combined with reverse transcription was used to detect viral RNA in peripheral blood mononuclear cells (PBMC) or synovial fluid (SF) cells. The patients with RA had newly diagnosed disease (duration < or = 1 year). The controls were patients with other arthropathies. RESULTS: Rubella genomic RNA was not detected in SF cells from patients with early RA or from controls, or in PBMC from patients with RA. It was found in PBMC of one of 46 patients with other arthropathies. Mumps or measles genomic RNA was detected in PBMC samples from 1.8% (1/54) and 9.3% (5/54) of RA, respectively, and from 4.3% (2/46) and 6.5% (3/46) of control patients. The SF cell samples harbored mumps or measles RNA in 4.8% (2/42) and 7.1% (3/42) of patients with RA, respectively; the corresponding value was 6.5% (2/31) for control patients, for both mumps and measles. CONCLUSION: Our findings suggest rubella, mumps, or measles do not play a role in the etiopathogenesis of RA.

Ligase chain reaction in detection of Chlamydia DNA in synovial fluid cells.

Synovial fluid cells from 12 patients with reactive arthritis (ReA) triggered by Chlamydia trachomatis were studied for the presence of Chlamydia DNA using the ligase chain reaction (LCR) LCx (Abbott) and the polymerase chain reaction (PCR) Amplicor (Roche). In addition, peripheral blood leucocytes from 11 of these patients were analysed by LCR. As controls, seven patients with newly diagnosed rheumatoid arthritis (RA) were included. Chlamydia trachomatis DNA was detectable by LCR in samples of synovial fluid cells from 4/12 patients with C. trachomatis-triggered ReA, and in none by PCR. Chlamydia trachomatis DNA was not detectable in the synovial fluid cells of the seven RA patients by either method, neither was C. trachomatis DNA detectable in the peripheral blood leucocytes of the ReA patients (0/11) or controls (0/6) by LCR. The LCR technique may be useful in the demonstration of Chlamydia DNA in synovial fluid cells.

Increase of HLA-DRB1*0408 and -DQB1*0301 in HLA-B27 positive reactive arthritis.

OBJECTIVE: To study HLA class II association in reactive arthritis. METHODS: 63 patients with reactive arthritis and 46 with rheumatoid arthritis were included in the study. HLA-DR alleles were determined by using a sequence specific PCR method. Oligonucleotide hybridisation was used for definition of DRB1*04 subtypes and DQB1 alleles. HLA-B27 was determined by standard microcytotoxity test or by PCR. HLA-B27 subtyping was made by sequencing. RESULTS: 46 (73%) of 63 patients with reactive arthritis were HLA-B27 positive and 24 (38%) were HLA-DRB1*04 positive. When haplotypes were inferred according to the known associations between DRB1 and DQB1 alleles, the frequency of DRB1*04-DQB1*0301 haplotype was found to be 13% (12/92) in HLA-B27 positive reactive arthritis patients, in contrast to 0% in HLA-B27 negative reactive arthritis (P = 0.04) and 1% in random controls (P = 0.0009). However, this combination was also found in 5% of 84 HLA-B27 positive control haplotypes, showing a linkage disequilibrium between B27 and this particular class II haplotype. HLA-DRB1*0408 subtype was found in 8/24 (33%) of the HLA-DRB1*04 alleles in patients with reactive arthritis, accounting for most DQB1*0301 haplotypes, but only in 5/55 (9%) of the DRB1*04 alleles in random controls (P = 0.017). All reactive arthritis patients with this subtype were positive for HLA-B27. DRB1*04-DQB1*0302 haplotype was increased in patients with rheumatoid arthritis (28/92, 30%) compared with reactive arthritis (12/126, 10%) or with the controls (12/100, 12%; P = 0.003). HLA-B*2705 was by far the dominant B27 subtype both in reactive arthritis patients with the particular DRB1*0408-DQB1*0301 haplotype and in controls. It was found in 11 out of 12 DR analysed patients, as well as in 10 out of 11 randomly selected B27 positive controls. CONCLUSIONS: Although no single class II allele was found to be increased among patients with reactive arthritis, HLA-B27, DRB1*0408, and DQB1*0301 might exert a haplotypic effect in the pathogenesis of reactive arthritis, or they may be markers of a subset of B27 haplotypes conferring susceptibility.

Peripheral blood neutrophil leukotriene B4 release and migration in rheumatoid arthritis.

The present study was designed to compare peripheral blood neutrophil migration and leukotriene (LT) release between patients with rheumatoid arthritis (RA) and healthy controls and to correlate the neutrophil functions with clinical disease activity. Nineteen patients with moderately active RA and 19 age and sex matched healthy volunteers participated in this study. Isolated peripheral blood neutrophils from RA patients released equal amounts of LTB4 but their random migration was enhanced as compared with neutrophils from healthy controls. LTB4 release in whole blood was significantly lower in samples from RA patients than in those from the healthy volunteers (13.5 +/- 1.4 and 19.1 +/- 1.4 ng/10(6) neutrophils respectively; P < 0.001). LTB4 release from isolated RA neutrophils correlated with the levels of C-reactive protein, duration of morning stiffness and Ritchie articular swelling index. Concentrations of hyaluronate, cyclic AMP and 13, 14-dihydro-15-keto prostaglandin were not different between patients with RA and healthy volunteers. Neither was there any difference in TXB2 production by platelets during blood clotting. In conclusion, peripheral blood neutrophils of RA patients seem to be primed and/or activated as their random migration is enhanced as compared with those of healthy volunteers. In RA, LTB4 release from peripheral blood neutrophils seems to reflect the clinical activity of the disease. However, RA neutrophils released smaller (in whole blood) or equal (isolated cells) amount of LTB4 as compared with the respective controls. These contradictory findings suggest that LTB4 release from peripheral blood neutrophils has no major role in the regulation of disease activity in rheumatoid arthritis.

Predictive value of synovial fluid analysis in estimating the efficacy of intra-articular corticosteroid injections in patients with rheumatoid arthritis.

The predictive relevance of synovial fluid analysis and some other variables for the efficacy of intra-articular corticosteroid injections in 30 patients with rheumatoid arthritis and hydropsy in a knee joint was evaluated in a prospective study. At the onset of the study, the knee joints were aspirated and 30 mg triamcinolone hexacetonide injected intra-articularly. The circumferences and the tenderness scores of the knee joints were measured at onset, after two months, and at the end of the six months' follow up. Of the variables studied, synovial fluid C4, percentage of synovial fluid polymorphonuclear leucocytes, blood haemoglobin, and serum C3 correlated significantly with the decrease in knee joint circumference after two months, whereas only the percentage of synovial fluid polymorphonuclear leucocytes correlated significantly after six months. Between the patients with and without improvement in the tenderness scores of the knee joints, only serum IgM differed at the examination after two months; this was higher in patients whose scores showed no improvement.