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ABSTRACT: To investigate how inflammation and metabolic syndrome (MetS) are associated with adipokine levels in patients with inflammatory arthritis.
Fifty-four female patients with arthritis were enrolled in the study. Twenty (37%) of these patients had MetS, which was diagnosed according to the definition of the International Diabetes Federation (IDF). Interleukin (IL)-6 and four adipokines (resistin, leptin, adiponectin, and adipsin) were determined by immunoassay. Healthy women with body mass index (BMI) between 22 and 25 kg/m(2) served as controls.
The patients with arthritis had higher levels of resistin than the healthy controls. This difference was clear in patients without MetS (17.4 in patients vs. 10.8 ng/mL in controls, p < 0.001), and even higher resistin levels were found in the patients with MetS (20.7 ng/mL; p < 0.001 vs. healthy controls; and p = 0.095 vs. patients without MetS). In the patients with arthritis and MetS, resistin correlated positively with IL-6 (Pearson's r = 0.5, p = 0.03). Leptin levels were increased in arthritis patients with MetS as compared to healthy controls, but not in patients without MetS. The statistically significant difference between patients with MetS and controls remained when leptin was adjusted with BMI. Accordingly, adiponectin levels were lower in patients with MetS than in healthy controls (p < 0.05). Leptin, adiponectin, and adipsin did not correlate with the inflammatory cytokine IL-6 or with C-reactive protein (CRP).
The results show that high resistin levels are associated with arthritis independently of MetS, whereas leptin is increased only in arthritis patients with MetS.
Scandinavian journal of rheumatology 04/2011; 40(4):256-62. · 2.51 Impact Factor
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Scandinavian journal of rheumatology 01/2011; 40(3):236-8. · 2.51 Impact Factor
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ABSTRACT: To describe the effects of rituximab therapy in patients with rheumatoid arthritis (RA) in routine clinical practice in Finland.
Data were collected retrospectively from patient records in five rheumatology clinics in Finland. All RA patients treated during 2005-2008 (n = 81) were included. Information on disease-modifying anti-rheumatic drugs (DMARDs), DMARD combinations, and biologics prior to rituximab use was collected as well as treatment responses after initiating rituximab therapy. The Disease Activity Score using 28 joint counts (DAS28) was used to determine disease activity and European League Against Rheumatism (EULAR) responses.
Mean disease duration was 14 (range 0-47) years and the median number of prior DMARDs and biologics used were 7 (1-12) and 2 (0-4), respectively. Efficacy analysis was performed on 57 patients with available DAS28 data at treatment onset and follow-up visits. Median DAS28 declined from 6.07 (3.19-7.70) to 3.99 (1.53-6.55) by the first rituximab treatment course. Altogether 77% of the patients achieved a EULAR response, 26% with a good response including 18% with remission. Furthermore, the patients treated concomitantly with DMARDs other than methotrexate (MTX) achieved a EULAR response slightly more often than the patients on MTX (85% vs. 70%) only. A second course of rituximab was given to 48% of the patients on an average of 9 months after initial therapy, with the median DAS28 score declining further to 3.49 (0.1-5.74). Safety and tolerability assessment of the 81 patients indicates rituximab to be well tolerated.
Rituximab can effectively control disease activity in patients with active disease and poor response to previous therapies, in combination with MTX but also with other DMARDs.
Scandinavian journal of rheumatology 08/2009; 38(5):323-7. · 2.51 Impact Factor
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ABSTRACT: To study the effect of isometric neck strength exercises on upper cervical stability in patients with rheumatoid arthritis (RA).
Twenty patients with a mean (SD) age of 58 (9) years and duration of RA of 27 (10) years volunteered for the study. Lateral radiographs of the cervical spine were taken to measure the current atlantoaxial distance (AAD) in flexion and extension. Maximal isometric neck flexion and extension strength values were measured by a dynamometer. Thereafter, AADs were measured from radiographs taken at 80-90% resistance of maximal strength.
According to the full flexion radiographs at baseline, the patients were classified into three groups: eight patients without anterior atlantoaxial subluxation (aAAS) [AAD = 2.1 (2-3) mm], seven with unstable aAAS [AAD = 6.6 (5-8) mm], and five with stable aAAS [AAD = 5.5 (5-7) mm]. During resisted flexion the AAD decreased by 5 (3-7) mm (p<0.001) in the unstable aAAS group, while in the other two groups the changes were minor. During resisted extension the AAD increased by 3 (2-6) mm (p<0.001) in the cases with unstable aAAS only.
Isometric exercising towards flexion decreases the AAD in cases with unstable aAAS. Submaximal loading of the neck extensors by pushing the back of the head against the resistance even in the neutral position of the cervical spine leads to a decrease in the width of the cervical spine canal and is not recommended in unstable aAAS.
Scandinavian journal of rheumatology 07/2008; 37(5):343-7. · 2.51 Impact Factor
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E Jaakkola,
I Herzberg,
K Laiho,
M C N M Barnardo,
J J Pointon, M Kauppi,
K Kaarela,
E Tuomilehto-Wolf,
J Tuomilehto,
B P Wordsworth,
M A Brown
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ABSTRACT: To determine the influence of HLA-B27 homozygosity and HLA-DRB1 alleles in the susceptibility to, and severity of, ankylosing spondylitis in a Finnish population.
673 individuals from 261 families with ankylosing spondylitis were genotyped for HLA-DRB1 alleles and HLA-B27 heterozygosity/homozygosity. The frequencies of HLA-B27 homozygotes in probands from these families were compared with the expected number of HLA-B27 homozygotes in controls under Hardy-Weinberg equilibrium (HWE). The effect of HLA-DRB1 alleles was assessed using a logistic regression procedure conditioned on HLA-B27 and case-control analysis.
HLA-B27 was detected in 93% of cases of ankylosing spondylitis. An overrepresentation of HLA-B27 homozygotes was noted in ankylosing spondylitis (11%) compared with the expected number of HLA-B27 homozygotes under HWE (4%) (odds ratio (OR) = 3.3 (95% confidence interval, 1.6 to 6.8), p = 0.002). HLA-B27 homozygosity was marginally associated with reduced BASDAI (HLA-B27 homozygotes, 4.5 (1.6); HLA-B27 heterozygotes, 5.4 (1.8) (mean (SD)), p = 0.05). Acute anterior uveitis (AAU) was present in significantly more HLA-B27 positive cases (50%) than HLA-B27 negative cases (16%) (OR = 5.4 (1.7 to 17), p<0.004). HLA-B27 positive cases had a lower average age of symptom onset (26.7 (8.0) years) compared with HLA-B27 negative cases (35.7 (11.2) years) (p<0.0001).
HLA-B27 homozygosity is associated with a moderately increased risk of ankylosing spondylitis compared with HLA-B27 heterozygosity. HLA-B27 positive cases had an earlier age of onset of ankylosing spondylitis than HLA-B27 negative cases and were more likely to develop AAU. HLA-DRB1 alleles may influence the age of symptom onset of ankylosing spondylitis.
Annals of the Rheumatic Diseases 07/2006; 65(6):775-80. · 8.73 Impact Factor
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ABSTRACT: To study the prevalence of cervical spine subluxation in patients with rheumatoid arthritis waiting for orthopaedic surgery, and symptoms that might be associated with the disorders.
194 patients with rheumatoid arthritis were referred for orthopaedic surgery at Jyväskylä Central Hospital, 154 (79%) of whom volunteered for the present study including clinical examination, laboratory tests, radiographs of the cervical spine, hands, and feet, and self report questionnaires. Definition of anterior atlantoaxial subluxation (aAAS) was >3 mm and of subaxial subluxation (SAS)>or=3 mm. Atlantoaxial impaction (AAI) was analysed following to the Sakaguchi-Kauppi method.
67 patients (44%) had cervical spine subluxation or previous surgical fusion. The prevalence of aAAS, AAI, SAS, or previous fusion was 27 (18%), 24 (16%), 29 (19%), and 8 (5%), respectively; 69% of patients with cervical spine subluxations (those with fusions excluded) reported neck pain, compared with 65% of patients without subluxations (p=0.71). The prevalence of occipital, temporal, retro-orbital, and radicular pain in upper extremities was similar in patients with or without cervical spine subluxations (54% v 43%; 17% v 31%; 25% v 24%; 47% v 48%, respectively). However, patients with subluxations were older, had longer disease duration, more active disease, poorer function according to the Health Assessment Questionnaire, and had more often erosive disease.
Asymptomatic cervical spine subluxation is common in patients with rheumatoid arthritis waiting for orthopaedic surgery. Regardless of symptoms, the possibility of cervical spine subluxation in patients with severe rheumatoid arthritis should be considered in preoperative evaluation.
Annals of the Rheumatic Diseases 07/2006; 65(7):884-8. · 8.73 Impact Factor
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M F Seldin,
R Shigeta,
K Laiho,
H Li,
H Saila,
A Savolainen,
M Leirisalo-Repo,
K Aho,
E Tuomilehto-Wolf,
K Kaarela, M Kauppi,
H C Alexander,
A B Begovich,
J Tuomilehto
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ABSTRACT: Several studies have identified the PTPN22 allelic variant 1858 C/T that encodes the R620W amino-acid change as a putative susceptibility factor in autoimmune diseases. The current study was undertaken to examine a large cohort of Finnish rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) subjects using both population control and, importantly, family-based association methods. The latter is particularly important when, as is the case for the 1858 C/T polymorphism, the frequency of the variant allele (T) differs in both major ancestral populations and in subpopulations. The analysis of rheumatoid factor-positive 1030 RA probands from Finland provides strong support for association of this variant in both population studies (allele specific odds ratio (OR)=1.47, 95% confidence interval (CI)=1.27-1.70, P=3 x 10(-7)) and in family studies (P<10(-6)). In contrast, no allelic association was seen with JIA (230 probands) and only weak evidence for a genotypic effect of 1858T homozygotes was observed in this population.
Genes and Immunity 12/2005; 6(8):720-2. · 3.87 Impact Factor
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ABSTRACT: To describe the functional capacity for daily activities in old people with clinical rheumatoid arthritis (including juvenile rheumatoid arthritis (JRA)) in a population based cohort.
A cohort of 700 people was randomly collected from the population older than 75 years in a Finnish town. Altogether 601 persons (86%) participated. Data were collected from clinical records and by interview, clinical examination, and questionnaire. Ability to carry out activities of daily living (ADL) was assessed by the Barthel index, and the IADL (instrumental activities of daily living) by the Lawton and Brody questionnaire.
16 people had clinical rheumatoid arthritis (one with JRA). The prevalence was 16/601 (2.7% (95% confidence interval, 1.7% to 4.5%)). Eight patients with rheumatoid arthritis (50%) obtained the best possible ADL figures, while three (19%) had very poor results. Seven (44%) could not dress themselves without help. Three (19%) were unable to walk, and five (31%) could not climb stairs. Sex and age adjusted results showed no statistical difference (ADL and IADL) between patients with clinical rheumatoid arthritis and rest of the cohort. Four patients (25%) had dementia, which was associated with the poor functional capacity.
The prevalence of the disease was unexceptional. The ability of old people with rheumatoid arthritis to carry out activities of daily living did not differ from the general population, but the disease may lead to severe disability on an individual level, especially when associated with dementia. It therefore remains a considerable challenge to the health care and social systems.
Annals of the Rheumatic Diseases 02/2005; 64(1):56-8. · 8.73 Impact Factor
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ABSTRACT: We have developed and validated a semi-automated fluorescent method of genotyping human leucocyte antigen (HLA)-DRB1 alleles, HLA-DRB1*01-16, by multiplex primer extension reactions. This method is based on the extension of a primer that anneals immediately adjacent to the single-nucleotide polymorphism with fluorescent dideoxynucleotide triphosphates (minisequencing), followed by analysis on an ABI Prism 3700 capillary electrophoresis instrument. The validity of the method was confirmed by genotyping 261 individuals using both this method and polymerase chain reaction with sequence-specific primer (PCR-SSP) or sequencing and by demonstrating Mendelian inheritance of HLA-DRB1 alleles in families. Our method provides a rapid means of performing high-throughput HLA-DRB1 genotyping using only two PCR reactions followed by four multiplex primer extension reactions and PCR-SSP for some allele groups. In this article, we describe the method and discuss its advantages and limitations.
Tissue Antigens 08/2004; 64(1):88-95. · 2.59 Impact Factor
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ABSTRACT: Abstract We have developed and validated a semi-automated fluorescent method of genotyping human leucocyte antigen (HLA)-DRB1 alleles, HLA-DRB1*01–16, by multiplex primer extension reactions. This method is based on the extension of a primer that anneals immediately adjacent to the single-nucleotide polymorphism with fluorescent dideoxynucleotide triphosphates (minisequencing), followed by analysis on an ABI Prism 3700 capillary electrophoresis instrument. The validity of the method was confirmed by genotyping 261 individuals using both this method and polymerase chain reaction with sequence-specific primer (PCR-SSP) or sequencing and by demonstrating Mendelian inheritance of HLA-DRB1 alleles in families. Our method provides a rapid means of performing high-throughput HLA-DRB1 genotyping using only two PCR reactions followed by four multiplex primer extension reactions and PCR-SSP for some allele groups. In this article, we describe the method and discuss its advantages and limitations.
Tissue Antigens 06/2004; 64(1):88 - 95. · 2.59 Impact Factor
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ABSTRACT: We report a case of acute anterior uveitis (AAU) in association with an outbreak of Campylobacter jejuni infection, with the first estimation of the incidence of AAU triggered by Campylobacter, and discuss reactive ophthalmological complications (AAU, iritis, and conjunctivitis) attributable to Campylobacter.
Scandinavian Journal of Rheumatology 02/2004; 33(1):55-7. · 2.47 Impact Factor
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E Jaakkola,
A M Crane,
K Laiho,
I Herzberg,
A-M Sims,
L Bradbury,
A Calin,
S Brophy, M Kauppi,
K Kaarela,
B P Wordsworth,
J Tuomilehto,
M A Brown
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ABSTRACT: To determine whether genetic polymorphisms in or near the transforming growth factor beta1 (TGFB1) locus were associated with susceptibility to or severity of ankylosing spondylitis (AS).
Five intragenic single-nucleotide polymorphisms (SNP) and three microsatellite markers flanking the TGFB1 locus were genotyped. Seven hundred and sixty-two individuals from 184 multiplex families were genotyped for the microsatellite markers and two of the promoter SNPs. One thousand and two individuals from 212 English and 170 Finnish families with AS were genotyped for all five intragenic SNPs. A structured questionnaire was used to assess the age of symptom onset, disease duration and disease severity scores, including the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index).
A weak association was noted between the rare TGFB1 +1632 T allele and AS in the Finnish population (P = 0.04) and in the combined data set (P = 0.03). No association was noted between any other SNPs or SNP haplotype and AS, even among those families with positive non-parametric linkage scores. The TGFB1 +1632 polymorphism was also associated with a younger age of symptom onset (English population, allele 2 associated with age of onset greater by 4.2 yr, P = 0.05; combined data set, allele 2 associated with age of onset greater by 3.2 yr, P = 0.02). A haplotype of coding region SNPs (TGFB1 +869/+915+1632 alleles 2/1/2) was associated with age of symptom onset in both the English parent-case trios and the combined data set (English data set, haplotype 2/1/2 associated with age of onset greater by 4.9 yr, P = 0.03; combined data set, haplotype 2/1/2 associated with greater age of onset by 4.2 yr, P = 0.006). Weak linkage with AS susceptibility was noted and the peak LOD score was 1.3 at distance 2 cM centromeric to the TGFB1 gene. No other linkage or association was found between quantitative traits and the markers.
This study suggests that the polymorphisms within the TGFB1 gene play at most a small role in AS and that other genes encoded on chromosome 19 are involved in susceptibility to the disease.
Rheumatology 02/2004; 43(1):32-8. · 4.06 Impact Factor
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ABSTRACT: To examine whether functional radiography and functional magnetic resonance imaging (MRI) are equally efficient in detecting the extent of unstable anterior atlantoaxial subluxation (aAAS) in rheumatic patients.
23 patients with unstable aAAS (diagnosed by functional radiography) were examined by functional MRI because of a neck symptom. Twenty two patients had rheumatoid arthritis and one had juvenile idiopathic arthritis. aAAS was diagnosed if the anterior atlantoaxial diameter (AAD) was >3 mm and was considered unstable if the AAD differed by >2 mm between flexion and extension radiographs. The AAD was measured from radiographs (flexion and extension) and MRI images (flexion and neutral).
The extent of aAAS during flexion measured by radiography was greater than that found by MRI in all 23 patients (mean difference 3 mm (95% confidence interval 2 to 4)). In four (17%) patients flexion MRI could not demonstrate aAAS detected by radiography. The difference between the AAD measurements during flexion by these two methods was substantial (that is, >or=4 mm) in nine (39%) cases. Severe aAAS (>or=9 mm) was seen in 15 (65%) patients by functional radiography and in four (17%) by functional MRI.
The magnitude of aAAS was often substantially smaller when measured by functional MRI rather than by functional radiography. Thus one cannot rely on the result of functional MRI alone; functional radiographs are needed to show the size of unstable aAAS. The maximal extent of the subluxation must be taken into account when the possible compression of neural structures is evaluated by MRI.
Annals of the Rheumatic Diseases 03/2003; 62(3):254-6. · 8.73 Impact Factor
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ABSTRACT: To evaluate the validity and reliability of the Finnish version of the Arthritis Impact Measurement Scales (AIMS2) in Finnish patients with rheumatoid arthritis (RA).
The reliability of the Finnish AIMS2 (Finn-AIMS2) questionnaire was assessed by test retest procedure and internal consistency of health-status scales. Construct validity was assessed by factor analysis, and convergent validity by correlation coefficients, with several disease activity and functional status variables.
Internal consistency was 0.79-0.89 and test retest reliability 0.72-0.97. Factor analysis identified three factors: physical, psychosocial, and pain. There were strong correlations between the Finn-AIMS2 health-status scales and the Health Assessment Questionnaire (HAQ).
The Finn-AIMS2 questionnaire is a reliable and valid instrument for measuring health status in middle-aged Finnish patients with RA. The results also support the applicability of AIMS2 in comparisons in multinational studies.
Scandinavian Journal of Rheumatology 02/2003; 32(5):300-5. · 2.47 Impact Factor
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V Goedecke,
A M Crane,
E Jaakkola,
W Kaluza,
K Laiho,
D E Weeks,
J Wilson, M Kauppi,
K Kaarela,
J Tuomilehto,
B P Wordsworth,
M A Brown
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ABSTRACT: Genetic polymorphisms of the IL10 promoter region have been implicated in many autoimmune diseases, including seronegative spondyloarthropathies. We studied three SNPs (IL10-1087, -824, and -597) and two microsatellites (IL10R and IL10G) lying within the promoter region of IL10 for association with susceptibility to and clinical manifestations of ankylosing spondylitis (AS), a common form of spondyloarthritis. Four hundred and sixty-eight individuals from 182 Finnish families affected with AS were studied. No association between individual IL10 promoter region polymorphisms or marker haplotype was observed with susceptibility to AS, but weak association was noted between the IL10-597 and -824 SNPs and age of disease onset (P=0.01 for each SNP). The IL10.G4 allele was associated with BASFI (corrected for disease duration) (P=0.03). We conclude that IL10 promoter polymorphisms have no significant effect on susceptibility to AS, but may play a minor role in determining age of disease onset and disease severity.
Genes and Immunity 02/2003; 4(1):74-6. · 3.87 Impact Factor
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ABSTRACT: To assess the significance of ultrasonography (US) in detecting hip joint synovitis in patients with rheumatic diseases.
Forty patients with rheumatic disease and suspected hip joint synovitis underwent MRI and US of the hip joint. In addition to the throughout MRI evaluation, the anterior collum-capsule distance (CCD) was determined by both MRI and US. Thirteen healthy volunteers were examined with MRI to establish the criteria for normal findings in MRI when classifying hip joints to those with synovitis and those without. MRI was used as a gold standard.
Synovitis was found using MRI in 31 hips of 22 patients (9 patients had bilateral synovitis). The intraclass correlation was 0.61 between MRI and US in measuring CCD. In classifying hip joint synovitis with US, the sensitivity of the method was 87% and specificity 42%, when the CCD criterion for synovitis was determined to be > or = 7 mm. If the cut-off point was raised to 9 mm, the sensitivity decreased to 61% while specificity increased to 94%. A difference in CCD of > or = 1 mm between the hips as an additional criterion for synovitis increased the number of false-positive findings.
Measurement of CCD with US proved to be a rather inaccurate method to point out synovitis in rheumatic patients when using MRI as a reference. The main reason for this result was the thickened capsule, which US could not differentiate from a thickened synovium.
Acta Radiologica 01/2003; 44(1):72-8. · 1.37 Impact Factor
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Joint Bone Spine 01/2003; 69(6):622-3. · 2.27 Impact Factor
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ABSTRACT: Purpose: To assess the significance of ultrasonography (US) in detecting hip joint synovitis in patients with rheumatic diseases.Material and Methods: Forty patients with rheumatic disease and suspected hip joint synovitis underwent MRI and US of the hip joint. In addition to the throughout MRI evaluation, the anterior collum-capsule distance (CCD) was determined by both MRI and US. Thirteen healthy volunteers were examined with MRI to establish the criteria for normal findings in MRI when classifying hip joints to those with synovitis and those without. MRI was used as a gold standard.Results: Synovitis was found using MRI in 31 hips of 22 patients (9 patients had bilateral synovitis). The intraclass correlation was 0.61 between MRI and US in measuring CCD. In classifying hip joint synovitis with US, the sensitivity of the method was 87% and specificity 42%, when the CCD criterion for synovitis was determined to be ≥7 mm. If the cut-off point was raised to 9 mm, the sensitivity decreased to 61% while specificity increased to 94%. A difference in CCD of ≥1 mm between the hips as an additional criterion for synovitis increased the number of false-positive findings.Conclusion: Measurement of CCD with US proved to be a rather inaccurate method to point out synovitis in rheumatic patients when using MRI as a reference. The main reason for this result was the thickened capsule, which US could not differentiate from a thickened synovium.
Acta Radiologica 12/2002; 44(1):72 - 78. · 1.37 Impact Factor
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ABSTRACT: The aim of this radiographic study was to ascertain the extent of inflammatory cervical spine disorders in patients with rheumatoid arthritis (RA) complicated by secondary amyloidosis (SA). The study involved 147 patients with RA and SA, whose cervical spine radiographs were available. They were treated at the Rheumatism Foundation Hospital, Heinola, during the period 1989-2000 and had had RA for a mean of 24 years. The inflammatory abnormalities of the cervical spine were studied from radiographs taken at or after the diagnosis of SA during flexion and extension. One-hundred and eleven (76%) patients had subluxations, impaction or apophyseal joint ankylosis. Atlantoaxial impaction (AAI) was seen in 76 (52%) patients and anterior atlantoaxial subluxation (AAS) in 59 (40%). Apophyseal joint ankylosis was the third most frequent finding, seen in 34 (23%) cases. A combination of AAI and apophyseal joint ankylosis was noted in 26 (18%) patients. Eight (5%) patients had undergone surgery on the cervical spine. In conclusion, inflammatory and destructive changes are frequent in the cervical spine of patients with RA and SA. Characteristic changes are AAI and AAS. RA patients with SA have more severe disease than those in epidemiological studies when cervical spine disorders are concerned.
Clinical Rheumatology 07/2002; 21(3):227-30. · 2.00 Impact Factor
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ABSTRACT: To establish the incidence of clinically important inflammatory cervical spine abnormalities in radiographs of patients with psoriatic arthritis (PsA).
Patients were selected from a rheumatological outpatient clinic and one ward of the Rheumatism Foundation Hospital, Heinola, Finland, by examining 160 consecutive PsA cases. A total of 65 patients (38 women, 27 men) with PsA were identified who had cervical spine radiographs available. These were evaluated for inflammatory changes, and patient records studied for disease characteristics, laboratory and clinical findings.
In 12 cases (18%) inflammatory cervical spine changes were seen in the cervical spine radiographs. The most frequently detected was apophysial joint ankylosis, seen in seven patients (11%). Anterior atlantoaxial subluxation (aAAS) was seen in five (8%) and atlantoaxial impaction in three (5%). In 20 of the 40 patients who had the rotational range of neck motion measured the measurement was < or =45 degrees either to the left or the right side.
Inflammatory cervical spine changes were not commonly seen in radiographs of patients with PsA. Apophysial joint ankylosis and aAAS were detected most often. PsA may decrease the rotational range of neck motion significantly.
Annals of the Rheumatic Diseases 07/2002; 61(7):650-2. · 8.73 Impact Factor
