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Biomedical subjects

R Luukkainen

Publications and source records attributed to R Luukkainen.

At least 19 recordsLinked to original sources
PubMed2006

Poor relationship between joint swelling detected on physical examination and effusion diagnosed by ultrasonography in glenohumeral joints in patients with rheumatoid arthritis.

The purpose of this study was to assess the relationship between swelling detected on physical examination and effusion diagnosed by ultrasonography (US) in glenohumeral (GH) joints in patients with rheumatoid arthritis (RA). Fifty consecutive patients with RA entered the study and 20 healthy control persons formed a control group. Altogether 100 GH joints of the RA patients and 40 of the controls were evaluated. The clinical assessments were carried out by one doctor and the US investigations by another, and they were blinded to each other's results. The clinical examination and US gave similar results in 70 GH joints, whereas they differed in the remaining 30 GH joints. The kappa coefficient between these investigations was 0.202, showing poor agreement. These results showed poor agreement between the clinical assessment of swelling and effusion detected by US in GH joints. Therefore, US may considerably improve the accuracy of diagnosis of effusion in GH joints, which usually means synovitis in patients with RA.

Adult↗
PubMed2006

Biological treatment in rheumatic diseases: results from a longitudinal surveillance: adverse events.

The objective of this study was to assess the long-term safety and tolerability of biologicals in a clinical setting. Data on adverse events (AEs) have been collected over a 5-year period by means of detailed reports sent in to the National Register of Biological Treatment in Finland (ROB-FIN) and validated by information collected by the National Agency for Medicines. Three hundred and eight reports on AEs were filed, concerning a total of 248 patients; this corresponds to 17% of all patients in the ROB-FIN register who started biological treatments. Skin reactions and infections comprised 35 and 28% of the AEs, respectively. Some cases of tuberculosis and other infections, heart failure and demyelinating conditions were seen. Our work demonstrates no unexpected AEs in a Finnish patient cohort consisting of rheumatoid arthritis and spondylarthropathy patients, although many of them were treated with combination treatments in common use in Finland. Biological treatment appears safe in the hands of the Finnish rheumatologists.

Adolescent↗
PubMed2005

Monetary value of lost productivity over a five year follow up in early rheumatoid arthritis estimated on the basis of official register data on patients' sickness absence and gross income: experience from the FIN-RACo trial.

OBJECTIVE: To explore the monetary value of rheumatoid arthritis related loss of productivity in patients with early active disease. METHODS: In a prospective cohort substudy of the FIN-RACo Trial, 162 patients with recent onset rheumatoid arthritis, aged 18 to 65 years and available to the workforce, were followed up for five years. Loss of work productivity in euros 2002 was estimated by data on absence for sickness and on income (human capital approach) from official databases. Treatment responses were evaluated by area under the curve (AUC) of the ACR-N measure and by increase in number of erosions in radiographs of hands and feet. The health assessment questionnaire (HAQ) at six months was linked to the International Classification of Functioning, Disability and Health (ICF). RESULTS: In all, 120 (75%) patients, women more often (82%) than men (61%) (p=0.002), lost work days. The mean lost productivity per patient-year was euro7217 (95% confidence interval (CI), 5561 to 9148): for women, euro6477 (4858 to 8536) and for men, euro8443 (5389 to 12,898). There was an inverse correlation with improvement: euro1101 (323 to 2156) and euro14 952 (10,662 to 19,852) for the highest and lowest quartiles of AUC of ARC-N, respectively. Lost productivity was associated with increase in the number of erosions and with disability in "changing and maintaining body position" subcategory of the ICF. CONCLUSIONS: Despite remission targeted treatment with disease modifying antirheumatic drugs, early rheumatoid arthritis results in substantial loss of productivity. A good improvement in the disease reduces the loss markedly.

Adolescent↗
PubMed2005

CD4+ CD25+ T cells with the phenotypic and functional characteristics of regulatory T cells are enriched in the synovial fluid of patients with rheumatoid arthritis.

CD4(+) CD25(+) regulatory T (T(reg)) cells play a critical role in the maintenance of peripheral tolerance and the prevention of autoimmunity. In the present study, we have explored the characteristics of CD4(+) CD25(+) T(reg) cells in patients with rheumatoid arthritis (RA). The frequency and phenotype of CD4(+) CD25(+) T cells in paired samples of synovial fluid (SF) and peripheral blood (PB) from patients with RA and PB from normal controls were analysed. An increased frequency of CD4+ cells T cells expressing CD25 was detected in SF compared to PB from patients with RA. No significant difference was observed in the numbers of CD4(+) CD25(+) T cells in PB from patients and controls. SF CD4(+) CD25(+) T cells expressed high levels of CTLA-4 (both surface and intracellular), GITR and OX40, as well as Foxp3 transcripts. Functionally, SF CD4(+) CD25(+) T cells were impaired in their proliferative responses and could suppress the proliferation of their CD4(+) CD25(-) counterparts. In conclusion, these data demonstrate that CD4(+) CD25(+) T(reg) cells, with the potential to regulate the function of effector T cells and antigen-presenting cells, accumulate in the synovium of patients with RA.

Adult↗
PubMed2004

Relationship between clinically detected joint swelling and effusion diagnosed by ultrasonography in elbow joints in patients with rheumatoid arthritis.

The aim of this study was to compare the relationship between clinically detected swelling and effusion diagnosed by ultrasonography (US) in elbow joints in patients with rheumatoid arthritis (RA). Fifty consecutive patients with RA entered the study and 20 healthy persons formed a control group. Altogether 100 elbow joints of the RA patients and 40 of the controls were studied. All the clinical assessments were performed by one doctor and the US investigations by the other and they were blinded to each others results. In 77 elbow joints of the RA patients the clinical assessment and the US gave similar results, whereas they differed in the remaining 23 joints. The kappa coefficient between these investigations was 0.371. In the control group no elbow joint showed either swelling in the clinical assessment or effusion in the US investigation. The results of this study indicate that clinical assessment of swelling and evaluation of effusion by US in elbow joints in patients with RA show only fair agreement. Thus, US may improve the accuracy of diagnosis of synovitis in many cases in these patients.

Adult↗
PubMed2004

Sindbis viruses and other alphaviruses as cause of human arthritic disease.

Amongst the arthritis-causing arboviruses, i.e. those spread by insects, the alphavirus group is of special interest. These viruses occasionally cause vast outbreaks, such as O'nyong-nyong in Africa in 1959. In Fennoscandia, Sindbis-related Ockelbo, Pogosta, or Karelian fever viruses have been found to cause significant morbidity. The major symptoms in addition to joint inflammation are fever, fatigue, headache and rash. The joint symptoms may persist for weeks, even months. The diagnosis is based on the clinical picture and serology. The causative viruses are closely related but not identical. It appears that at least in Finland the Pogosta disease is more common than thought, and the symptoms may often be overlooked. Several factors related to the viruses, their hosts, and global environmental changes may affect the spread of these viruses. All over the world arbovirus-caused diseases have increased, because of global changes.

Alphavirus Infections↗
PubMed2004

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.

Arthritis, Rheumatoid↗
PubMed2003

The prevalence of antibodies against Sindbis-related (Pogosta) virus in different parts of Finland.

OBJECTIVE: To study the occurrence of Sindbis-related (Pogosta) disease in Finland by serological means. METHODS: A total of 2250 serum samples from five different areas were included in the study. Four hundred samples were collected from healthy blood donors and 1850 samples from patients who were suspected to have some viral infection. Antibodies of IgG and IgM classes against Pogosta virus were measured. RESULTS: Eleven per cent of 2250 samples were positive for IgG and 0.6% were positive for IgM class antibodies against Pogosta virus. The antibody prevalence in Finland was almost equally distributed, being highest in western Finland (17%) and lowest in southern and northern Finland (9%). Of all samples with IgG class antibodies, 25% were taken from children under 10 yr of age. CONCLUSIONS: The prevalence of antibodies against Pogosta virus was much higher than we expected. Additionally, they were detected from all locations studied and not only in eastern Finland, which has been thought to be the main endemic area for this disease. Pogosta disease has been considered to affect mainly middle-aged persons, but our results indicate a high prevalence also among children.

Adolescent↗
PubMed2003

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.

Acute Disease↗
PubMed2001

HLA haplotype analysis in Finnish patients with rheumatoid arthritis.

OBJECTIVE: To further characterize the HLA gene products that play an important role in the pathogenesis of rheumatoid arthritis (RA). METHODS: One hundred thirty-four haplotypes from 67 Finnish RA patients and 77 control haplotypes were analyzed for HLA-DRB1 loci, associated alleles of the HLA-DQB1 locus, alleles of the type 2 transporter-associated antigen processing (TAP2) genes, and HLA-B27. In addition, a panel of microsatellite markers within the HLA class I and class III regions was studied. RESULTS: The frequency of HLA-DRB1*04 in the haplotypes of RA patients was found to be 34% (45 of 134) compared with 14% (10 of 72) in control haplotypes (P = 0.004). The frequency of HLA-DRB1*13 was decreased in RA haplotypes (4%, or 5 of 134) in contrast to control haplotypes (24%, or 17 of 72) (P = 0.000031). The decrease in DRB1*13 was not secondary to the increase in DRB1*04, since it was also found among DRB1*04-negative haplotypes (P < 0.001). The DRB1*13-associated DQB1*0604 allele was similarly decreased in RA haplotypes (P = 0.025). The TAP2I allele of I/J dimorphism was increased in RA patients (85%, or 114 of 134) as compared with controls (69%, or 49 of 71) (P = 0.011). Of the tumor necrosis factor (TNF) microsatellite alleles, TNFa6 and TNFb5 were found to be increased in RA haplotypes (for a6 27% versus 5% in controls [P = 0.00043], and for b5 43% versus 26% in controls [P = 0.037]). CONCLUSION: Both protection-associated and susceptibility-associated alleles can be found among HLA class II genes, and the results suggest that loci outside DR/DQ may contribute to the pathogenesis of RA.

Arthritis, Rheumatoid↗
PubMed2001

The coexistence of systemic lupus erythematosus and multiple sclerosis in a mother and daughter.

The occurrence of both multiple sclerosis (MS) and systemic lupus erythematosus (SLE) has previously been described in several members within the same family and in twins of successive generations, but the finding of both diseases in one patient is a great rarity. We here report on a rare coexistence of MS and SLE both in mother and daughter. Both patients fulfill the diagnostic criteria of primary-progressive subtype of MS as well as SLE. The finding constitutes supporting evidence of a common genetic background for these two autoimmune disorders.

Adult↗
PubMed2001

Non-steroidal anti-oestrogens inhibit the differentiation of synovial macrophages into dendritic cells.

BACKGROUND: Dendritic cells (DC) have been suggested to play an important role in the pathogenesis of rheumatoid arthritis (RA). Agents that inhibit DC differentiation and function may have a therapeutic value in the treatment of RA. OBJECTIVE: To examine the effect of the non-steroidal anti-oestrogens toremifene and tamoxifen on the differentiation of synovial fluid (SF) macrophages into DC. METHODS: SF macrophages from patients with RA were cultured with interleukin (IL)-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF) in the presence or absence of anti-oestrogens. The expression of cell surface markers on SF antigen-presenting cells (APC) was studied by flow cytometry. The capacity of SF APC to stimulate allogeneic T cells was studied using the mixed lymphocyte reaction. The production of tumour necrosis factor-alpha, IL-10 and transforming growth factor-beta1 was studied using ELISA. RESULTS: Anti-oestrogens inhibited the differentiation of SF macrophages into DC and the capacity of SF macrophage-derived DC to stimulate allogeneic T cells. CONCLUSIONS: By inhibiting the differentiation of SF macrophages into DC, non-steroidal anti-oestrogens may have beneficial effects in RA.

Aged↗
PubMed2001

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.

Adult↗
PubMed2001

Type I collagen degradation does not diminish with RA disease duration.

OBJECTIVE: To assess the relation between type I collagen degradation and the duration of rheumatoid arthritis (RA). METHODS: The serum concentrations of cross linked carboxyterminal telopeptide of type I collagen (ICTP) measured earlier in a community based series (90 patients) and a hospital based series (59 patients) were re-evaluated with reference to the duration of RA. RESULTS: The serum ICTP showed a positive correlation with the duration of the disease in the hospital based series (r(s)=0.40, p<0.01) but not in the community based one (r(s)=0.18, p=0.10). CONCLUSIONS: Type I collagen degradation predominantly reflecting pathological bone destruction does not seem to diminish in longlasting RA.

Arthritis, Rheumatoid↗
PubMed2000

Combination drug therapy retards the development of rheumatoid atlantoaxial subluxations.

OBJECTIVE: To compare the efficacy of combination therapy with disease-modifying antirheumatic drugs (DMARDs) versus single therapy with DMARDs in the prevention of early cervical spine changes in patients with rheumatoid arthritis (RA). METHODS: One hundred ninety-five patients with recent-onset RA (mean disease duration 8 months) were randomly assigned to receive a combination of DMARDs (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone) or a single DMARD with or without prednisolone. After 2 years of followup, cervical spine radiographs were taken of 176 of these patients (85 in the combination-therapy group and 91 in the single-therapy group). These radiographs were evaluated, and the findings were correlated with the therapy strategies as well as with peripheral joint destruction and clinical and laboratory variables describing the disease activity. RESULTS: Anterior atlantoaxial subluxation (aAAS), atlantoaxial impaction (AAI; i.e., vertical subluxation), and subaxial subluxation (SAS) were found in only 6 (3.4%), 2 (1.1%), and 5 (2.8%) of the patients, respectively. Interestingly, none of the patients in the combination-therapy group had aAAS or AAI. The incidences of aAAS and AAI in the single-therapy group were 6.6% and 2.2%, respectively. SAS was present in 2 patients (2.2%) in the single-therapy group and in 3 patients (3.5%) in the combination-therapy group. The difference in the incidence of aAAS between the treatment groups was statistically significant (P = 0.029). None of the patients with cervical spine changes achieved remission of RA during the study. CONCLUSION: In the present study, the incidence of cervical spine subluxations in patients treated with single-drug therapy was in accord with findings of previous studies. However, none of the patients in the combination-therapy group had aAAS or AAI. These findings suggest that early, aggressive combination-DMARD therapy with sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone can prevent or retard the development of rheumatoid atlantoaxial disorders.

Adult↗
PubMed2000

Interleukin-15 up-regulates the expression of CD154 on synovial fluid T cells.

To investigate the role of the CD40-CD154 interaction in rheumatoid arthritis (RA), we analysed the expression of CD154 on CD3+ and CD4+ T cells in synovial fluid (SF) from patients with RA and in peripheral blood (PB) from patients and normal controls. As interleukin (IL)-15 is a potent activator of synovial T cells we wanted to study whether IL-15 also regulated the expression of CD154 on these T cells. Freshly isolated synovial T cells did not express significant levels of CD154, as evaluated using flow cytometry, whereas the expression of CD86 and human leucocyte antigen (HLA)-DR was significantly elevated on SF T cells when compared with PB T cells from patients or controls. Synovial T cells could up-regulate their CD154 expression following activation with phorbol 12-myristate 13-acetate (PMA) + ionomycin or anti-CD3 + anti-CD28 monoclonal antibodies (mAbs), but the maximal level of expression remained lower than in control T cells. IL-15 significantly increased the expression of CD154 on SF and PB T cells from patients, whereas IL-2 had minimal effects. Furthermore, IL-15 induced extensive proliferation in SF T cells. Our results show that SF T cells up-regulate the expression of CD154 in the presence of IL-15, a cytokine present in the synovium of patients with RA. These results further emphasize the role of IL-15 in the pathogenesis of RA.

Adult↗