Search PubMed⌕ Search

Biomedical subjects

M Leirisalo-Repo

Publications and source records attributed to M Leirisalo-Repo.

At least 73 records · Page 4Linked to original sources
PubMed2000

Ultrasonography in the quantification of arterial involvement in Takayasu's arteritis.

OBJECTIVE: To evaluate the accuracy of ultrasonography (US) in the detection and quantification of arterial involvement in Takayasu's arteritis (TA). METHODS: The common carotid and subclavian arteries, and the abdominal aorta of 15 patients with TA were studied by Color Doppler (CD) US and Doppler spectral analysis and compared with angiography. RESULTS: The mean difference (+/-SD) between the percent luminal stenoses measured at angiography and by CD US was 2.0+/-10.3% for the common carotid artery, 4.0+/-23.6% for the subclavian artery and -1.3+/-16.8% for the abdominal aorta. The differences were not statistically significant. However, the agreement of the methods was less than satisfactory as shown by the wide standard deviations. CONCLUSIONS: More efforts are needed to improve the less than optimal agreement of US with angiography regarding the severity of individual stenoses. The technique performs best in the study of carotid arteries.

Adult↗
PubMed2000

Prediction of disease progression in early rheumatoid arthritis by ICTP, RF and CRP. A comparative 3-year follow-up study.

OBJECTIVE: To test the predictive value of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP; a marker of type I collagen degradation), rheumatoid factor (RF) and C-reactive protein (CRP) for disease progression in patients with early rheumatoid arthritis (RA) METHOD: We tested the value of baseline values of RF, CRP and ICTP for the prediction of radiological joint progression over 3 yr in 63 consecutive patients with early RA who were treated with the 'saw-tooth strategy'. RESULTS: Age- and sex-adjusted risks as odds ratios (95% confidence intervals) of elevated serum ICTP, RF positivity and increased CRP for progressive joint disease (defined as an increase of > 20 in Larsen's index on radiographs of the hands and feet) were 3.9 (1.3, 11.9), 3.9 (1.0, 15.5) and 2.6 (0.9, 7.5), respectively. Better prediction was achieved when the tests were used in combination, and where there was both elevated ICTP and positive RF the odds ratio was 9.1 (2.5, 32.9). This test combination showed good sensitivity and specificity (71 and 77%, respectively), with a positive predictive value of 65% and a likelihood ratio of 3.1. CONCLUSION: This kind of risk profile, in which the tests used reflect different aspects of the disease process, may be useful in early disease assessment to find patients who will need the most active drug therapy.

Adolescent↗
PubMed2000

Effect of age on 3 year outcome in early rheumatoid arthritis.

OBJECTIVE: To investigate the effect of age on clinical and radiological outcome and on efficacy and tolerance of antirheumatic therapy in early rheumatoid arthritis (RA). METHODS: In a prospective 3 year study 113 patients (83 women, 30 men) were divided into 2 groups according to age at onset of disease: before (n = 55) and after 55 years of age (n = 58). For clinical outcome, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor, Ritchie index, and number of swollen joints were measured. Radiological progression was analyzed by Larsen score. The principles of the "sawtooth" strategy were applied in the treatment of all patients. RESULTS: At baseline, inflammatory activity (ESR, CRP) and the Larsen score for hands were significantly higher in patients with late onset RA (LORA) and they also developed more extraarticular symptoms compared to patients with early onset RA (EORA). However, no differences were found in Ritchie index, number of swollen joints, or CRP values between the groups. Also during the followup there was a trend toward increased inflammatory activity (ESR) among LORA patients. After the initiation of antirheumatic therapy a parallel improvement in clinical activity was observed in the 2 groups. The frequencies of remissions, side effects, and withdrawals due to drug inefficacy did not differ significantly between the 2 groups. The radiological progression was also comparable. CONCLUSION: The onset of RA was more active in patients with LORA. However, the clinical course and the radiological progression were parallel in LORA and EORA patients. The "sawtooth" therapy was equally tolerated in both patient groups.

Adolescent↗
PubMed2000

Expression of alpha4-integrins on human neutrophils.

alpha4 Integrins are important adhesion molecules mediating binding of lymphocytes, monocytes, and eosinophils to multiple cellular and extracellular ligands. Mature neutrophils have been recently suggested to express alpha4-integrins as well. We studied whether human neutrophils can synthesize alpha4-integrins upon activation in vitro or in vivo. Two anti-alpha4 mAbs, but not multiple subclass-matched non-binding controls, reacted with granulocytes in an inducer and time-dependent manner. Nevertheless, staining with Ig subclass-specific second-stage reagents surprisingly revealed that commercial anti-alpha4 mAbs contain two distinct Igs, the alpha4-specific IgG1 and an IgG2a of an unknown specificity. We showed that in vitro inductions used by us and others only induce the binding of nonspecific IgG2a from the commercial HP2/1 to activated neutrophils. By reverse-transcriptase polymerase chain reaction, alpha4 mRNA was not detectable in purified neutrophils. Our results show that alpha4 integrin protein and mRNA are absent from normal and stimulated human neutrophils.

Antigens, CD↗
PubMed1999

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.

Adult↗
PubMed1999

Salmonella-triggered reactive arthritis: use of polymerase chain reaction, immunocytochemical staining, and gas chromatography-mass spectrometry in the detection of bacterial components from synovial fluid.

OBJECTIVE: To investigate whether microbial components are present in the cells of synovial fluid or peripheral blood from patients with Salmonella-triggered reactive arthritis (ReA). METHODS: Synovial fluid cells and/or peripheral blood cells from 23 patients with Salmonella-triggered ReA and from 19 control patients with newly diagnosed rheumatoid arthritis were studied using 3 different polymerase chain reaction (PCR) techniques and immunocytochemical staining. Muramic acid from the synovial fluid was studied by gas chromatography-mass spectrometry. RESULTS: Salmonella chromosomal DNA was not detectable in the synovial fluid cells and peripheral blood leukocytes of patients with Salmonella ReA. Initially, positive reactions were observed in the synovial fluid cells and peripheral blood leukocytes of 3 of 17 and 3 of 18 patients with ReA, respectively, but in the subsequent PCR studies, these findings were not reproducible. Salmonella-specific antigen was detectable by immunofluorescence in the synovial fluid cells and peripheral blood leukocytes of 4 of 11 and 2 of 7 patients with ReA, respectively. Muramic acid was present in 2 of 15 synovial fluid samples from patients with ReA, but the bacterial cultures from synovial fluid were negative. CONCLUSION: These findings indicate the presence of bacterial degradation products, but not bacterial DNA, in the inflamed joints of patients with Salmonella-triggered ReA.

Adolescent↗
PubMed1999

Modulation of peripheral blood mononuclear cell activation status during Salmonella-triggered reactive arthritis.

OBJECTIVE: To determine the activation status of mononuclear cells in the peripheral circulation during the acute phase and the recovery phase of Salmonella-triggered reactive arthritis (ReA). METHODS: Peripheral blood mononuclear cells (PBMC) were obtained from 8 patients with Salmonella infection (4 with ReA and 4 without) and were studied by reverse transcription-polymerase chain reaction for messenger RNA (mRNA) of proinflammatory and antiinflammatory cytokines, by flow cytometry (FC) for cell surface activation and adhesion molecules, by immunofluorescence (IF) microscopy for bacterial antigens, and by FC, IF, and DNA fragmentation on gel for signs of apoptosis. RESULTS: During the acute phase of the infection, PBMC were activated in all patients, as characterized by high levels of expression of CD14, CD11b, and CD11c on monocytes. In the patients with ReA, PBMC also had the capacity to produce interleukin-1beta (IL-1beta), IL-6, IL-8, IL-10, and tumor necrosis factor alpha. During the amelioration of disease, monocyte activation was decreased in all patients. A complete down-regulation of CD14 was detected only in the patients with ReA, whereas the expression of CD14 in the patients without ReA was positive and was similar to that in healthy controls. In addition, cytokine mRNA levels decreased regardless of the presence of Salmonella antigens in blood cells in all 4 patients with ReA. CONCLUSION: High levels of expression of some activation and adhesion molecules and elevated levels of mRNA for certain cytokines that are predominantly produced by monocytes were found in PBMC from patients with acute Salmonella-triggered ReA, which suggests that these cells are activated. On the other hand, complete down-regulation of CD14 and a marked decrease in the cytokine production capacity during amelioration of the disease suggest that suppression of PBMC activity might be involved in recovery from ReA.

Acute-Phase Reaction↗
PubMed1999

Agalactosyl IgG is elevated in patients with active spondyloarthropathy.

Patients with rheumatoid arthritis or with Crohn's disease have deficient galactosylation of serum IgG [Gal(0)]. To study whether such deviation occurs in patients with spondyloarthropathy (SPA), we studied the percentage incidence of Gal(0) corrected for age [Gal(0)corr] in 47 SPA patients undergoing ileocolonoscopy and correlated the findings with clinical variables and prognosis of the patients. Gal(0)corr was elevated in 36% of the patients. Such patients had a higher number of inflamed joints (P < 0.02), higher ESR (P < 0.001) and CRP (P < 0.001). Elevated Gal(0)corr was also of prognostic significance: at 6-month follow-up those with elevated levels had a higher number of inflamed joints (P < 0.02) and ESR (P < 0.05). The presence of high Gal(0)corr did not associate with gut inflammation. In conclusion, a proportion of SPA patients has elevated levels of Gal(0), the amount of which correlates with severity of the disease and is a prognostic marker for chronicity of the disease.

Adult↗
PubMed1999

Juvenile chronic arthritis in adult life: a study of long-term outcome in patients with juvenile chronic arthritis or adult rheumatoid arthritis.

We compared the prognostic factors and outcome of 30 patients with juvenile chronic arthritis (JCA) extending into adult life with those of 30 patients with adult rheumatoid arthritis (RA) at a university adult rheumatology clinic; pairs were matched for sex and duration of disease (mean 8 years). One-third of JCA patients had seronegative polyarticular disease and another third had oligoarticular disease. In a third of the JCA patients, the clinical presentation changed during the follow-up. Over half of the RA patients had seropositive polyarticular and a one-third had seronegative polyarticular disease. Fewer seropositive patients were recorded in the JCA group than in the RA group both at the beginning (16.7% versus 56.7%; p=0.003) and at the end of the follow-up (14.3% versus 59.3%; p=0.001). JCA patients developed less radiographic changes than RA patients (46.7% versus 76.7%; p=0.034); oligoarthritis in the JCA group had the best prognosis whereas seropositive polyarthritis in the RA group had the worst prognosis. Significantly more patients with JCA than RA (60% versus 23%; p=0.009) were in remission at the end of the follow-up. In conclusion, when studied in adult life, the long-term prognosis is better in patients with JCA than in those with RA.

Adolescent↗
PubMed1999

Enterobacterial infection modulates major histocompatibility complex class I expression on mononuclear cells.

Major histocompatibility complex (MHC) class I expression is reduced in several viral infections, but it is not known whether the same happens during infections caused by intracellular enterobacteria. In this study, the expression of MHC class I antigens on peripheral blood mononuclear cells (PBMC) from 16 patients with Salmonella, Yersinia, or Klebsiella infection was investigated. During or after the acute infection, the expression of MHC class I antigens was markedly decreased in eight patients, all with genotype HLA-B27, and six out of eight with reactive arthritis (ReA). A significant decrease of monomorphic MHC class I was found in three patients, of HLA-B27 in eight (P<0.05) and of HLA-A2 in two. However, patients negative for the HLA-B27 genotype, or healthy HLA-B27-positive individuals, did not have a significant decrease of MHC class I antigens. During the decreased expression on the cell surface, intracellular retention of MHC class I antigens was observed, whereas HLA-B27 mRNA levels did not vary significantly. This is the first evidence that enterobacterial infection may down-regulate expression of MHC class I molecules in vivo and that down-regulation is predominant in patients with the HLA-B27 genotype.

Adolescent↗
PubMed1999

Chlamydia pneumoniae as a triggering infection in reactive arthritis.

OBJECTIVE: To determine the role of Chlamydia pneumoniae as a triggering infection in reactive arthritis (ReA). METHODS: Sixty patients with acute arthritis were screened for the evidence of triggering infections. In all patients, bacterial stool cultures, culture of Chlamydia trachomatis in urethra/cervix, and/or bacterial serology were studied. Chlamydia pneumoniae antibodies were measured by specific microimmunofluorescence test. RESULTS: Thirty-five of 60 patients fulfilled the diagnostic criteria for ReA. Thirty-one patients had microbial/serological evidence of preceding infection due to Salmonella, Yersinia, Campylobacter or Chlamydia trachomatis, or they had enteritis or urethritis prior to arthritis. Four additional patients had high antibody titre for C. pneumoniae. Three of these four patients had preceding lower respiratory symptoms, and were positive for HLA-B27. The clinical picture of C. pneumoniae-positive ReA patients was similar to that of ReA patients with other definite aetiology. CONCLUSION: Chlamydia pneumoniae is a triggering factor in approximately 10% of patients with acute ReA.

Adult↗
PubMed1999

Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components.

OBJECTIVES: To investigate the potential clinical benefit of a combination therapy. METHODS: 205 patients fulfilling the ACR criteria for rheumatoid arthritis (RA), not treated with disease modifying antirheumatoid drugs previously, with an early (< or = 1 year duration), active (Disease Activity Score (DAS) > 3.0), rheumatoid factor and/or HLA DR 1/4 positive disease were randomised between sulphasalazine (SASP) 2000 (maximum 3000) mg daily (n = 68), or methotrexate (MTX) 7.5 (maximum 15) mg weekly (n = 69) or the combination (SASP + MTX) of both (n = 68). RESULTS: The mean changes in the DAS during the one year follow up of the study was -1.15, -0.87, -1.26 in the SASP, MTX, and SASP + MTX group respectively (p = 0.019). However, there was no statistically significant difference in terms of either EULAR good responders 34%, 38%, 38% or ACR criteria responders 59%, 59%, 65% in the SASP, MTX, and SASP + MTX group respectively. Radiological progression evaluated by the modified Sharp score was very modest in the three groups: mean changes in erosion score: +2.4, +2.4, +1.9, in narrowing score: +2.3, +2.1, +1.6 and in total damage score: +4.6, +4.5, +3.5, in the SASP, MTX, and SASP + MTX groups respectively. Adverse events occurred more frequently in the SASP + MTX group 91% versus 75% in the SASP and MTX group (p = 0.025). Nausea was the most frequent side effect: 32%, 23%, 49% in the SASP, MTX, and SASP + MTX groups respectively (p = 0.007). CONCLUSION: This study suggests that an early initiation therapy of disease modifying drug seems to be of benefit. However, this study was unable to demonstrate a clinically relevant superiority of the combination therapy although several outcomes were in favour of this observation. The tolerability of the three treatment modalities seems acceptable.

Antirheumatic Agents↗
PubMed1999

Systemic inflammatory response syndrome without systemic inflammation in acutely ill patients admitted to hospital in a medical emergency.

Criteria of the systemic inflammatory response syndrome (SIRS) are known to include patients without systemic inflammation. Our aim was to explore additional markers of inflammation that would distinguish SIRS patients with systemic inflammation from patients without inflammation. The study included 100 acutely ill patients with SIRS. Peripheral blood neutrophil and monocyte CD11b expression, serum interleukin-6, interleukin-1beta, tumour necrosis factor-alpha and C-reactive protein were determined, and severity of inflammation was evaluated by systemic inflammation composite score based on CD11b expression, C-reactive protein and cytokine levels. Levels of CD11b expression, C-reactive protein and interleukin-6 were higher in sepsis patients than in SIRS patients who met two criteria (SIRS2 group) or three criteria of SIRS (SIRS3 group). The systemic inflammation composite score of SIRS2 patients (median 1.5; range 0-8, n=56) was lower than that of SIRS3 patients (3.5; range 0-9, n=14, P=0.013) and that of sepsis patients (5.0; range 3-10, n=19, P<0.001). The systemic inflammation composite score was 0 in 13/94 patients. In 81 patients in whom systemic inflammation composite scores exceeded 1, interleukin-6 was increased in 64 (79.0%), C-reactive protein in 59 (72.8%) and CD11b in 50 (61.7%). None of these markers, when used alone, identified all patients but at least one marker was positive in each patient. Quantifying phagocyte CD11b expression and serum interleukin-6 and C-reactive protein concurrently provides a means to discriminate SIRS patients with systemic inflammation from patients without systemic inflammation.

Acute Disease↗
PubMed1999

Conversion of patients with rheumatoid arthritis from the conventional to a microemulsion formulation of cyclosporine: a double blind comparison to screen for differences in safety, efficacy, and pharmacokinetics.

OBJECTIVE: To assess whether patients with rheumatoid arthritis (RA) may be converted, on a milligram-to-milligram basis, from conventional cyclosporin A (CyA, Sandimmun) to the microemulsion formulation (Neoral) with maintenance of longterm safety, and to compare cyclosporin A (CyA) pharmacokinetics between formulations. METHODS: In this double blind, multicenter, parallel group study, 51 patients receiving stable conventional CyA maintenance treatment were randomized to continue conventional CyA (n = 27) or to convert to CyA microemulsion (n = 24) and were monitored for 52 weeks. Trough blood CyA levels were measured before and at intervals after conversion. CyA steady-state area under the curve was assessed one week before and 2 and 6 weeks after randomization in 15 patients in each treatment arm. CyA trough levels and pharmacokinetic results remained unknown to investigators throughout the study. CyA doses were titrated as necessary on the basis of clinical evaluation and disease activity assessments. RESULTS: Initial mean daily doses were 3.5 mg/kg/day (conventional CyA) and 3.3 mg/kg/day (CyA microemulsion) and did not change significantly during the study. The mean bioavailability of CyA from the microemulsion formulation was 23% higher than from conventional CyA. Replicate assessments indicated a more reproducible pharmacokinetic profile with CyA microemulsion. The overall incidence and nature of adverse events and changes in vital signs and laboratory variables were similar in both groups. No clinically relevant differences in efficacy were found between treatments. No loss of efficacy and no tolerability problems occurred after conversion from conventional to microemulsion CyA. CONCLUSION: Existing CyA dosing guidelines, formulated for conventional CyA, are suitable for longterm CyA microemulsion therapy of patients with RA. These results indicate the pharmacokinetic advantages of the microemulsion formulation.

Antirheumatic Agents↗
PubMed1999

Recurrent reactive arthritis associated with urinary tract infection by Escherichia coli.

We describe a patient with recurrent Escherichia coli urinary tract infection followed by recurrent reactive arthritis. During a 9 year period the patient developed 4 episodes of arthritis. During each attack, triggering infections were thoroughly investigated but no other causative infection was found. Although the urinary tract is not routinely targeted for triggering infections for reactive arthritis, we suggest that urinary tract infections should be included in the diagnostic investigations of patients with acute arthritis.

Acute Disease↗