[Show abstract][Hide abstract] ABSTRACT: To study the reproductive health history in women with systemic lupus erythematosus (SLE) compared to population controls.
A total of 206 female SLE patients were interviewed regarding demographic and disease data, menstruation, use of contraception and hormone replacement therapy (HRT), infertility, and pregnancies. The control group consisted of 1037 women from the general population of similar age and socioeconomic status living in the same region.
In SLE women compared to population controls, mean age at menarche (13.3 vs. 13.2 years) and frequency of infertility (16% vs. 16%) were similar but menopause occurred earlier (44.9 vs. 46.8 years, p = 0.01). Current use of oral contraceptives (OCs) was less common than in controls [18% vs. 28%, odds ratio (OR) 0.55, 95% CI 0.3-1.0] while previous use of progesterone-containing intrauterine devices (IUDs) was more common (13% vs. 5%, OR 3.2, 95% CI 1.9-5.4). Current use of HRT was similar (22% vs. 21%) but SLE patients had started the use earlier (43.2 vs. 47.1 years, p = 0.003). Mean number of pregnancies was lower in SLE patients compared to controls (2.3 vs. 2.5, p = 0.046) and in lupus nephritis patients compared to SLE patients without nephritis (1.9 vs. 2.5, p = 0.01). No difference was found in the occurrence of spontaneous and induced abortions compared to controls, but pregnancy-associated complications were more common in SLE women.
When compared to population controls women with SLE are normally fertile, use less OCs and more IUDs, have earlier menopause and use HRT as frequently. Family size is reduced, especially in lupus nephritis patients, and pregnancy-associated complications are more common.
[Show abstract][Hide abstract] ABSTRACT: Anti-citrulline antibodies are highly specific to rheumatoid arthritis (RA) and are thus helpful in differential diagnosis. Early and aggressive disease modifying anti-rheumatic drug (DMARD) therapy is essential for a positive treatment result in cases of RA. Remission during the 1st year of treatment predicts permanent remission, milder joint damage and better functional ability. It is recommended that patients with an unsatisfactory response to DMARDs, including methotrexate and a combination of DMARDs, should be treated primarily with TNF blockers, and non-responders with rituximab or abatacept. RA is an independent risk factor for cardiovascular diseases. The assessment of cardiovascular risk must not be forgotten in daily practice.
[Show abstract][Hide abstract] ABSTRACT: We studied causes of death (CoDs) between 1952 and 1991 assessed by a clinician before autopsy and then determined at autopsy by a pathologist in 369 subjects with rheumatoid arthritis (RA) and 370 subjects without RA (non-RA). We analysed clinical data for RA subjects between 1973 and 1991. In RA subjects, leading autopsy-based CoDs were RA, cardiovascular diseases and infections. Between diagnoses of CoDs by the clinician and those determined by the pathologist, RA subjects had lower agreement than did the non-RA regarding coronary deaths (Kappa reliability measure: 0.33 vs. 0.46). In non-RA subjects, autopsy-based coronary deaths showed a decline since the 1970s with no such decline in RA. Between subjects treated at any time during RA with disease-modifying anti-rheumatic drugs and those without, autopsy-based CoDs were similar. Coronary death being less accurately diagnosed in RA subjects may indicate that coronary heart disease in RA patients often remains unrecognized.
Rheumatology International 11/2008; 28(12):1245-52. DOI:10.1007/s00296-008-0685-6 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study the impacts of 1) the delay from the onset of symptoms to the institution of disease-modifying antirheumatic drug (DMARD) therapy, 2) two treatment strategies (treatment with a combination of DMARDs or with a single drug), and 3) the presence of HLA-DRB1 alleles (shared epitope) on the prediction of disease remission after 2 years in patients with early rheumatoid arthritis (RA).
In the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial, 195 patients with recent-onset RA (median duration 6 months) were randomly assigned to receive either 1) a combination of DMARDs (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone) or 2) a single DMARD with or without prednisolone. The presence of a shared epitope was tested for in 165 of the 178 patients completing the study. The additional variables of age, sex, presence of rheumatoid factor, number of fulfilled American College of Rheumatology criteria for the classification of RA, and length of delay from onset of symptoms to institution of therapy were entered into a logistic regression model to determine the significant predictors for remission at 2 years.
The delay to therapy (cut point of 4 months) was the only significant predictor for remission in patients treated using the single-DMARD strategy, while no variable was a significant predictor for remission in those treated using the combination-DMARD strategy. The frequency of achieving remission in the combination-DMARD group after 2 years was similar in patients with short (0-4 months) and long (>4 months) delay periods (11 of 26 patients and 22 of 53 patients, respectively [approximately 42% in each group]), while the corresponding frequencies in the single-DMARD group were 8 of 23 patients (35%) and 7 of 63 patients (11%) (P = 0.021). The presence of a shared epitope was not related to the induction of remission.
The delay of a few months from the onset of symptoms to institution of therapy decreases the ability of the traditional single-drug strategy to induce remission in early RA.
[Show abstract][Hide abstract] ABSTRACT: YKL-40 is a newly discovered major secretory protein of human chondrocytes and synoviocytes. We measured serum levels of YKL-40 in 52 patients with early onset rheumatoid arthritis (RA) by enzyme-linked immunosorbent assay (ELISA) during a 2-year prospective follow-up, correlating values with laboratory and clinical variables and radiographic progression. Levels at baseline before antirheumatic therapy were significantly higher in patients than in healthy controls. The levels of YKL-40 correlated with laboratory and clinical markers of disease activity both at baseline and during follow-up. Baseline YKL-40 values correlated with baseline Larsen scores but did not predict radiographic progression. Baseline and mean YKL-40 values did not differ between fast and slow radiological progressions. Mean YKL-40 levels correlated with the number of swollen joints but were not predictors of radiographic progression. These results suggest that in early RA, serum YKL-40 is an inflammatory marker correlating with disease activity. However, its levels do not predict clinical course or radiographic progression.
Rheumatology International 08/2001; 20(5):192-6. DOI:10.1007/s002960100115 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of a strict uncooked vegan diet on serum lipid and sterol concentrations were studied in patients with rheumatoid arthritis. The subjects were randomized into a vegan diet group (n 16), who consumed a vegan diet for 2-3 months, or into a control group (n 13), who continued their usual omnivorous diets. Serum total and LDL-cholesterol and -phospholipid concentrations were significantly decreased by the vegan diet. The levels of serum cholestanol and lathosterol also decreased, but serum cholestanol:total cholesterol and lathosterol:total cholesterol did not change. The effect of a vegan diet on serum plant sterols was divergent as the concentration of campesterol decreased while that of sitosterol increased. This effect resulted in a significantly greater sitosterol:campesterol value in the vegan diet group than in the control group (1.48 (SD 0.39) v. 0.72 (SD 0.14); P < 0.001). A higher concentration of campesterol compared with sitosterol is normal in omnivorous subjects and can be explained by lower absorption and esterification rates of sitosterol. Our results suggest that a strict uncooked vegan diet changes the relative absorption rates of these sterols and/or their biliary clearance.
British Journal Of Nutrition 03/2001; 85(2):137-9. DOI:10.1079/BJN2000234 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effect of treatment on the outcome of very early RA.
In a 3-year prospective study of 27 patients with very early RA (VERA) (symptoms <4 months before diagnosis) and 122 patients with early RA (symptoms between 4-24 months) the effect of active treatment on the clinical picture, functional capacity, and radiological progression was evaluated.
Initially VERA patients had a more active clinical picture and worse functional capacity. Despite a higher number of DMARDs used in VERA patients, C-reactive protein and Ritchie index remained significantly higher in these patients (although significant improvement occurred). They also had a more rapidly progressive disease (higher Larsen score/month of symptoms) during pre-treatment period, the progression of which was retarded with early, active DMARD therapy. By the end of 3 years, the rate of progression ran parallel in both groups.
Active treatment had an impact on the rate of radiological progression and clinical activity but not on the functional outcome in patients with initially active RA of short duration.
Scandinavian Journal of Rheumatology 02/2001; 30(3):143-8. · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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'.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: To investigate the effect of age on clinical and radiological outcome and on efficacy and tolerance of antirheumatic therapy in early rheumatoid arthritis (RA).
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.
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.
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.
The Journal of Rheumatology 04/2000; 27(3):638-43. · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
The Journal of Rheumatology 04/1999; 26(3):556-62. · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the original Larsen method and the proposed modification of the Larsen method with omission of scoring soft tissue swelling and periarticular osteoporosis, and the Sharp method in measurement of radiographic progression in early rheumatoid arthritis (RA).
Radiographs of hands and feet were assessed by the 3 scoring methods at Months 0 and 12 in 83 patients with recent onset RA. Sensitivity to change was determined using standardized response mean (SRM).
Highly significant radiographic progression was observed by all 3 methods. The modified Larsen method showed the largest SRM (0.88), but the differences were slight between the 3 scoring methods (SRM 0.80 for the original Larsen method, SRM 0.72 for the Sharp method). High interobserver reproducibility was observed for all methods tested.
In early RA the sensitivity to change of all 3 scoring methods was high, but in this patient population the newly modified Larsen method was the most responsive method.
The Journal of Rheumatology 07/1998; 25(6):1063-6. · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To clarify the role of the faecal flora in the diet-induced decrease of rheumatoid arthritis (RA) activity, 43 RA patients were randomized into two groups: the test group to receive living food, a form of uncooked vegan diet rich in lactobacilli, and the control group to continue their ordinary omnivorous diets. Based on clinical assessments before, during and after the intervention period, a disease improvement index was constructed for each patient. According to the index, patients were assigned either to a group with a high improvement index (HI) or to a group with a low improvement index (LO). Stool samples collected from each patient before the intervention and at 1 month were analysed by direct stool sample gas-liquid chromatography of bacterial cellular fatty acids. This method has proved to be a simple and sensitive way to detect changes and differences in the faecal microbial flora between individual stool samples or groups of them. A significant, diet-induced change in the faecal flora (P = 0.001) was observed in the test group, but not in the control group. Further, in the test group, a significant (P = 0.001) difference was detected between the HI and LO categories at 1 month, but not in the pre-test samples. We conclude that a vegan diet changes the faecal microbial flora in RA patients, and changes in the faecal flora are associated with improvement in RA activity.
British journal of rheumatology 02/1997; 36(1):64-8. DOI:10.1093/rheumatology/36.1.64
[Show abstract][Hide abstract] ABSTRACT: To investigate the outcome of early rheumatoid arthritis (RA) when treated according to the "sawtooth" strategy, and to compare the results with the findings of other studies.
In this prospective study, 142 patients with early RA were treated actively with slow-acting antirheumatic drugs (SAARDs) for an average of 6.2 years, and were closely monitored clinically. Several outcome measures were applied, and the results were compared with findings in previously described cohorts.
The mean cumulative number of SAARDs used during the study was 3.3. Treatment changes were made because of inefficacy more often than because of adverse events. The percentage of patients whose disease entered remission increased with time to 32% (45 of 142). Only 24% of the patients (34 of 142) had deterioration to Steinbrocker functional class III or IV. The "sawtooth" treatment strategy seemed to improve the outcome of the patients with early RA.
In the majority of patients with early RA, "sawtooth" therapy remains beneficial for at least 6 years. However, in one-fourth of the patients, the disease fails to respond to this drug treatment strategy.
[Show abstract][Hide abstract] ABSTRACT: The prognostic value of quantitative measurement of rheumatoid factor (RF) by immunoturbidimetry was evaluated in 78 patients with early rheumatoid arthritis (RA) during a 3-yr follow-up. After starting disease-modifying antirheumatic treatment, a significant improvement in conventional clinical and laboratory variables measuring disease activity was observed, while a steady increase was found in radiological progression. Initial RF levels correlated with radiologically determined joint damage up to 3 yr, whereas no correlation of other initially determined conventional variables of disease activity was found. High levels of RF at entry and persistent RF positivity during the follow-up were markers for destructive disease. Initial RF positivity alone was a sensitive predictor for later joint destruction, but quantitative measurement of the initial RF level and especially repeated measurements of RF seemed to add significantly to the prognostic value of RF in distinguishing between progressive and non-progressive disease in early RA.
British journal of rheumatology 01/1996; 34(12):1146-50. DOI:10.1093/rheumatology/34.12.1146
[Show abstract][Hide abstract] ABSTRACT: We compared the effects of intramuscular gold and sulphasalazine on early, active rheumatoid arthritis in 128 consecutive patients. Intramuscular gold was started in the first 70 consecutive patients and sulphasalazine in the subsequent 58 patients. The patient groups were comparable with regard to clinical characteristics. In both groups clinical and laboratory parameters improved, but there was no significant difference between the two groups. The clinical improvement was most pronounced during the first three months. However, despite the clinical improvement a clear progression in radiological changes was observed in both groups, 40% of the patients taking gold and 48% of patients taking sulphasalazine discontinued the treatment because of adverse drug reactions or inefficacy during the one year follow-up. Adverse drug reactions were the main reason in both groups. These findings suggest that intramuscular gold and sulphasalazine seem to have an equal, positive effect on symptoms and clinical variables, but that radiological progression does occur in most patients none the less.
[Show abstract][Hide abstract] ABSTRACT: The new assay of cross-linked carboxyterminal telopeptide of type I collagen (ICTP), a serum marker for bone collagen degradation, was evaluated in serial measurements of 66 patients with early RA during a 3-yr prospective study. Initially 51% of RA patients had elevated levels of serum ICTP compared to healthy controls. During the subsequent months after starting anti-rheumatic treatment, the mean ICTP levels decreased in parallel with the clinical and laboratory variables measuring disease activity. Despite marked clinical improvement with anti-rheumatic treatment, a steady increase in radiological progression of joints was observed. Throughout the follow-up serum ICTP levels correlated with inflammatory parameters and from the first year on with the radiological changes assessed annually. However, initial serum ICTP levels correlated better than the other variables of disease activity with the subsequent erosive progression of joints indicating that measurement of serum ICTP may serve as one of the prognostic markers for joint damage in early RA.
British journal of rheumatology 12/1994; 33(11):1012-6.
[Show abstract][Hide abstract] ABSTRACT: This study focuses on the consequences of T-lymphocyte activation in chronic polyarthritis in terms of expression of cell surface receptors interacting with extracellular matrix (ECM). The expression of the VLA group of integrins was studied on in vitro-stimulated peripheral-blood T cells, and on peripheral-blood and synovial-fluid mononuclear cells (MNC) of patients with polyarthritis. The VLA expression was measured by flow cytometry using monoclonal antibodies (MoAbs) against alpha-subunits of the VLA family. VLA-alpha 4 and VLA-alpha 5, but not VLA-alpha 1, were expressed on a major fraction of unstimulated peripheral-blood T cells both in the patients with polyarthritis and in healthy individuals. Two distinct populations, VLA-alpha 5-high and VLA-alpha 5-low, were found in resting peripheral-blood T lymphocytes. Two days after stimulation by phorbol 12-myristate 13-acetate (PMA) and concanavalin A, most T cells became VLA-alpha 5-high. In patients with chronic polyarthritis, the expression of VLA-alpha 1 and VLA-alpha 5 was always higher on synovial-fluid T cells than on peripheral-blood T cells. These results give further support to the hypothesis that upon activation the induction of the VLA adhesion-molecule expression may be a factor contributing to the accumulation of T cells in the inflamed synovium.
Scandinavian Journal of Immunology 03/1994; 39(2):189-94. · 1.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study focuses on the consequences of T-lymphocyte activation in chronic polyarthritis in terms of expression of cell surface receptors interacting with extracellular matrix (ECM). The expression of the VLA group of integrins was studied on in vitro-stimulated peripheral-blood T cells, and on peripheral-blood and synovial-fluid mononuclear cells (MNC) of patients with polyarthritis. The VLA expression was measured by flow cytometry using monoclonal antibodies (MoAbs) against α-subunits of the VLA family. VLA-α4 and VLA-α5, but not VLA-α1, were expressed on a major fraction of unstimulated peripheral-blood T cells both in the patients with polyarthritis and in healthy individuals. Two distinct populations, VLA-α5-high and VLA-α5-low, were found in resting peuplieral-blood T lymphocytes. Two days after stimulation by phorbol 12-myristate 13-acetatc (PMA) and concanavalin A, most T cells became VLA-α5-high. In patients with chronic polyarthritis, the expression of VLA-α1 and VLA-α5 was always higher on synovial-fluid T cells than on peripheral-blood T cells. These results give further support to the hypothesis that upon activation the induction of the VLA adhesion-molecule expression may be a factor contributing to the accumulation of T cells in the inflamed synovium.