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P Kurki

Publications and source records attributed to P Kurki.

At least 19 recordsLinked to original sources
PubMed2002

Long term efficacy and safety of cyclosporin versus parenteral gold in early rheumatoid arthritis: a three year study of radiographic progression, renal function, and arterial hypertension.

OBJECTIVE: To compare the three year safety and efficacy of cyclosporin and parenteral gold in the treatment of early, active, severe rheumatoid arthritis (RA), and to study the reversibility of cyclosporin associated renal dysfunction in patients who discontinued cyclosporin treatment. METHODS: The patients continued to receive cyclosporin or parenteral gold in an 18 month open extension to an 18 month randomised, parallel group study. The main efficacy variable was blinded evaluation of radiographic progression of joint damage. Safety variables included serum creatinine, calculated creatinine clearance, and blood pressure. RESULTS: Radiographic progression during follow up was similar in both groups. About 60% of the patients in the intention to treat groups (n=272) and about half of the patients in the completer groups (n=114) had definite radiographic progression in joint damage (increases >6 in the Larsen-Dale score), and about one in three also had substantial progression (>18 increase in Larsen-Dale score). Both systolic and diastolic blood pressure were significantly increased in the cyclosporin group compared with the gold group, and 12/139 (9%) versus 3/139 (2%) (p=0.03) had notably raised blood pressure. The mean serum creatinine increased by 28% at the treatment end point in the cyclosporin group as compared with 7% in the gold group. The mean calculated creatinine clearance was reduced by 16% and increased by 1% in the cyclosporin and gold groups, respectively, at the end of the study. At the final follow up visit after discontinuation of cyclosporin (at least three months after treatment was stopped) the mean serum creatinine was increased by 15% and creatinine clearance reduced by 16%. Sustained increases in serum creatinine at this post-treatment end point were mostly seen in patients with a raised serum creatinine during treatment of at least 50%. CONCLUSION: Three year changes in radiographic damage during cyclosporin and parenteral gold were similar in patients with early, active RA. Abnormal renal function and raised blood pressure were often seen in the cyclosporin treated patients.

Activities of Daily Living↗
PubMed2001

Association of autoantibodies to filaggrin with an active disease in early rheumatoid arthritis.

OBJECTIVE: To evaluate the clinical significance of antifilaggrin antibodies (AFA) measured by an enzyme linked immunosorbent assay (ELISA) in serial specimens from patients with recent onset rheumatoid arthritis (RA). METHODS: Filaggrin was purified from human skin and used as an antigen in ELISA. The AFA test was applied to five serial specimens from 78 patients with recent onset RA followed up for three years. Rheumatoid factor (RF) had been measured earlier from the same samples by quantitative immunoturbidimetry. RESULTS: The mean AFA level was highest at entry (54% positive), followed by a statistically significant decline at six months and a slight increase at three years. AFA were persistently positive in 23 patients and persistently negative in 28 patients. Eleven of the latter patients were persistently negative for RF. At study entry AFA levels correlated to some degree with RF levels. In general, raised AFA levels at entry were associated with an active and treatment resistant disease, but they did not predict radiological progression. CONCLUSIONS: The test for AFA has potential for an additional immunological test for RA.

Adult↗
PubMed2001

Treatment strategy, disease activity, and outcome in four cohorts of patients with early rheumatoid arthritis.

OBJECTIVE: To compare four different inception cohorts of patients with early rheumatoid arthritis (RA) with respect to treatment strategies, disease activity, and outcome during a five year follow up period. METHOD: Data from cohorts of patients with early RA, with a standardised assessment at least every six months for five years from four different centres, were included in one database. Owing to slight differences in the individual study designs, linearly interpolated values were calculated to complete the standard follow up schedule. RESULTS: Despite similar inclusion criteria, significant differences in demographic factors and baseline disease activity were found between the different cohorts. During the follow up an aggressive treatment strategy was followed in the Dutch and Finnish cohort, an intermediate strategy in the British cohort, and a conservative strategy in the Swedish cohort. A significant improvement in disease activity was seen in all cohorts, though the most rapid and striking improvement was seen in those receiving aggressive treatment. This resulted in less radiographic destruction in the long run. CONCLUSION: This observational study of cohorts of patients with early RA confirms that early aggressive treatment results not only in a more rapid reduction of disease activity but also in less radiographic progression in the long term.

Adult↗
PubMed1999

Antifilaggrin antibodies in recent-onset arthritis.

We evaluated the sensitivity and prognostic value of an enzyme-linked immunosorbent assay (ELISA) for the measurement of antifilaggrin antibodies (AFA), using filaggrin purified from human skin as an antigen. The AFA test was applied to a series of 306 patients with various recent-onset inflammatory joint diseases. The results were compared to those of the conventional immunofluorescence tests for antikeratin antibody (AKA) and antiperinuclear factor (APF) and of the rheumatoid factor (RF) tests from a previous study. There was a very good agreement between the results of the tests for APF and AFA (kappa-value 0.79 in patients with peripheral poly/oligoarthritis). The agreement between the tests for AKA and AFA was significant but less pronounced (kappa-value 0.50). The AFA test detected 10/22 of the RF-negative erosive cases, particularly those with a large number of erosive joints. Thus, the test for AFA supplements RF in the prediction of erosiveness.

Adult↗
PubMed1999

Role of HLA in congenital heart block: susceptibility alleles in mothers.

In congenital heart block (CHB), abnormal maternal immunisation leads to autoantibody production against SS-A/Ro and SS-B/La antigens. These maternal antibodies are transferred across the placenta to the unborn child and are believed to transmit irreversible immunological injury in developing foetal heart tissue, thus causing 3rd-degree atrioventricular block. The mothers may suffer from systemic lupus erythematosus (SLE) or primary Sjögren's syndrome (SS), but they may be asymptomatic. Women with primary SS show a typical autoimmune HLA antigen pattern, namely higher frequency of HLA B8 and DR3 than in the normal population. The HLA pattern may affect individual ability to resist infecting bacteria and viruses and to response in various ways to autoantigens. It is probable that other factors such as genetic regulation of immune response are involved in CHB. We compared the HLA class I and class II alleles of mothers having CHB children with those of women suffering from primary SS and having healthy children, and with those of healthy Finns. Antibodies against 52-kD and 60-kD SS-A/Ro and 48-kD SS-B/La antigens were compared between the two groups of mothers. Our results show that anti-SS-A/Ro antibody-positive mothers all show a strong association with known autoimmune-predisposing HLA alleles, however, the mothers of CHB children differ in some HLA class I alleles, and especially in HLA haplotypes, from mothers of healthy children. Mothers with HLA A1, Cw7, B8 and without B15 are at particularly high-risk of having CHB children.

Alleles↗
PubMed1998

Immune-mediated congenital heart block (CHB): identifying and counseling patients at risk for having children with CHB.

OBJECTIVE: To identify patterns of maternal antibodies associated with an increased risk of having a child with congenital heart block (CHB) and to provide a basis for counseling women with a previously affected child. METHODS: This retrospective clinical study of the obstetric histories of 46 Finnish women with a CHB child compared the strength and specificity of the immune response to SS-A/Ro and SS-B/La, as determined by immunoblot and ELISA, in 44 affected women with 85 women with systemic lupus erythematosus (SLE) and 32 women with primary Sjögren's syndrome (SS) with healthy children. RESULTS: High levels of anti-SS-A/Ro and anti-SS-B/La by practically all assays were associated with a significantly increased risk of having a CHB child. The best single test to identify high-risk mothers was anti-52 kd SS-A/Ro by immunoblot (OR 18.9), and it was the only assay to detect mothers at increased risk of CHB as compared with controls with primary SS. Low risk of CHB was indicated by undetectable or low levels of antibodies in the ELISA assays and no reactivity on immunoblot. Mothers with a previous child with CHB had a history of fetal loss (mostly spontaneous abortions) or a history of recurrent fetal losses (> or = 3) slightly more often than controls. Late-trimester obstetric complications in non-CHB pregnancies were insignificant. The relative risk for a female child compared with a male child to have CHB was 1.9 (1.2-2.9, P = .009), and the risk of the mother having another child with CHB was 12% (4 of 34). CONCLUSION: Although there is no unique antibody profile specific for CHB, mothers with a high or low risk of having a child with CHB can be identified. Female children appear to have an increased risk of CHB, but the risk of the mother having another child with CHB is low.

Abortion, Spontaneous↗
PubMed1998

Progression of joint damage in early active severe rheumatoid arthritis during 18 months of treatment: comparison of low-dose cyclosporin and parenteral gold.

OBJECTIVE: This study compared the progression of joint damage in patients with early active severe rheumatoid arthritis (RA) treated with cyclosporin or parenteral gold. METHODS: In this open, randomized, multicentre study with a blinded radiological endpoint, 375 patients who had suffered from active severe RA for <3 yr were randomized to be treated for 18 months with low-dose cyclosporin or parenteral gold. The groups were stratified with regard to corticosteroid use. Primary efficacy variables were numbers of erosions, erosion score and the Larsen-Dale joint damage score. RESULTS: Joint damage progressed at similar rates in both treatment arms. In both groups, patients receiving corticosteroids had less X-ray progression. Rheumatoid factor positivity, high swollen joint count, high erythrocyte sedimentation rate and pre-existing X-ray abnormalities predicted progression of joint damage. Although numbers of serious adverse events were similar, more gold patients (n = 65) than cyclosporin patients (n = 45) withdrew from study medication because of adverse events. CONCLUSION: Cyclosporin was comparable to parenteral gold in retarding progression of joint damage and was better tolerated in terms of adherence to therapy. The open label design should be kept in mind when assessing this difference.

Adolescent↗
PubMed1998

Purification of filaggrin from human epidermis and measurement of antifilaggrin autoantibodies in sera from patients with rheumatoid arthritis by an enzyme-linked immunosorbent assay.

BACKGROUND: The so-called antikeratin antibody (AKA) and the antiperinuclear factor (APF) that recognize proteins related to human epidermal filaggrin belong to the most specific serological markers of rheumatoid arthritis (RA). However, assays for the detection of AKA and APF are currently based on immunofluorescence, a method that is subject to arbitrary interpretation and inadequate standardization of the substrates. METHODS: Proteins extracted from human epidermis were separated by reversed-phase high-performance liquid chromatography (HPLC). Filaggrin-containing fractions, identified in immunoblotting by monoclonal antifilaggrin antibodies, were then subjected to gel filtration HPLC and, finally, to a second reversed-phase HPLC step. Tryptic digestion, amino acid sequencing and mass spectrometry were used to confirm the identity of the purified protein. Filaggrin was used as antigen in enzyme-linked immunosorbent assay (ELISA) to measure IgG class antifilaggrin antibodies. RESULTS: The filaggrin preparation obtained gave a single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, binding monoclonal antifilaggrin antibody in immunoblotting. Amino acid sequences of all 10 tryptic peptides analyzed were shown to originate from human filaggrin. Antifilaggrin antibody levels exceeded the 99th percentile level of 100 middle-aged blood donors in 26/55 (47%) RA sera. At a similar cutoff level 28/55 (51%) of the RA sera were positive in the AKA test. Of the 26 antifilaggrin-positive sera, 21 were also AKA-positive. CONCLUSION: Human filaggrin can be purified by standard biochemical techniques, despite the heterogeneity of the protein, and used in ELISA for testing autoantibodies to filaggrin. The sensitivity of the assay equals that of the AKA test.

Adult↗
PubMed1997

Serum immunoglobulins and the risk of rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is associated with several autoantibodies that can precede the clinical disease. The immunoglobulin concentrations in serum samples before illness were studied to learn more about the immunological process before RA. METHODS: A case-control study was nested within a Finnish cohort of 19,072 adults who had neither arthritis nor a history of it at the baseline examination during 1973-1977. By late 1989, 124 had developed RA, of which 89 were positive for rheumatoid factor (RF). Three controls per each incident case were individually matched for sex, age, and municipality. The concentrations of IgG, IgA, and IgM were measured from stored serum samples. RESULTS: Serum IgG before illness was found to be directly proportional to the risk of RF positive RA, and a non-linear association was present between serum IgA and the risk of RF positive RA. These associations were constant between men and women and other subgroups of the study population and not confounded by serum orosomucoid concentration, level of education, smoking, alcohol intake or body mass index. As adjusted for these factors, the odds ratios (95% confidence intervals) of RF positive RA in the lowest, mid, and highest tertiles of IgG distribution were 1.00, 1.55 (0.81, 2.97), and 2.22 (1.16, 4.26), and in the tertiles of IgA 1.00, 2.23 (1.14, 4.36), and 1.78 (0.89, 3.57), respectively. The associations persisted throughout the entire observation period but were most distinct when the period to the onset of clinical RA was > or = 10 years. IgM carried no predictive significance. None of the serum immunoglobulins predicted the development of RF negative RA. CONCLUSIONS: Increased IgG levels may reflect some, at present unknown process in the early events leading to the development of RA, typically occurring > or = 10 years before the onset of clinical disease.

Adult↗
PubMed1997

Antibody to stratum corneum (antikeratin antibody) and antiperinuclear factor: markers for progressive rheumatoid arthritis.

The purpose of this study was to examine the relationship between circulating antibodies to stratum corneum (AKA) and antiperinuclear factors (APF) on one hand, and the x-ray progression of joint damage in chronic poly/oligoarthritis on the other hand. The analysis involved 133 patients with either rheumatoid or nonspecific arthritis derived from a cohort of 442 patients with recent onset arthritis. The patients were followed up for eight years with regular clinical, laboratory, and radiological evaluations. Radiographic evidence of joint destruction was quantitated by a radiographic index based on the Larsen grading. AKA and APF were detected, either at entry or at follow-up, in 26 and 54 patients, respectively. Seventy-six of the 133 patients had developed erosions. All AKA-positive patients had a rheumatoid factor-positive erosive poly-arthritis. The presence of APF was also associated with a progressive arthritis although four APF-positive patients had a non-erosive disease. Neither AKA nor APF were able to distinguish a particularly severe form of progressive RA.

Adolescent↗
PubMed1996

Is continuous intranasal salmon calcitonin effective in treating axial bone loss in patients with active rheumatoid arthritis receiving low dose glucocorticoid therapy?

OBJECTIVE: To investigate the efficacy of intranasal salmon calcitonin (sCT) in treating axial bone loss in patients with rheumatoid arthritis (RA) taking low dose glucocorticoids. METHODS: In this open, multicenter study 32 women with RA were treated one year with sCT 100 IU/day and calcium (Ca) 500 mg/day; 31 women were treated with Ca alone. Bone mineral density (BMD) was measured at the lumbar spine and proximal femur (femoral neck, Ward's triangle, trochanter) before sCT therapy and again after 6 and 12 months. RESULTS: Among valid completers treated with sCT and Ca (n = 26), the mean BMD increased at the lumbar spine (L1-L4), femoral neck, and Ward's triangle. In contrast, valid completers treated with Ca (n = 23) showed bone loss at the spine (L1-L4), femoral neck, Ward's triangle, and trochanter area. The differences of the changes in BMD were statistically significant between these groups at the femoral neck, Ward's triangle, and trochanter. There were no significant differences between groups in bone loss over 12 months at the lumbar spine (L1-L4), although analysis of the upper segment (L1-L2) suggested some possible benefit of sCT. CONCLUSION: Intranasal sCT (100 IU/day) appears to have beneficial effects on bone loss at the proximal femur in patients with active RA treated with low dose glucocorticoids for 12 months; longer studies are needed to exclude transient bone remodelling effects.

Administration, Intranasal↗
PubMed1996

Diclofenac combined with cyclosporine in treatment refractory rheumatoid arthritis: longitudinal safety assessment and evidence of a pharmacokinetic/dynamic interaction.

OBJECTIVE: (1) To characterize potential changes in diclofenac pharmacokinetics and renal function in patients with rheumatoid arthritis (RA) treated with diclofenac and cyclosporine; (2) to prospectively collect longitudinal safety data during use of this drug combination. METHODS: Twenty patients with severe, treatment refractory RA were sequentially treated with stable doses of diclofenac (100-200 mg/day) for one month followed by diclofenac combined with cyclosporine (3 mg/kg/day) for one month. Pharmacokinetic profiles of diclofenac were obtained at the end of each treatment period. Combined therapy was continued for an additional 5 months, during which doses of both drugs could be individually titrated and safety data collected. RESULTS: During co-administration, diclofenac exposure doubled, as shown by an average 104% increase in the area-under-the-curve. Diclofenac half-life was not altered. Serum creatinine was significantly elevated from a baseline value of 0.8 +/- 0.1 mg/dl on diclofenac alone to 1.0 +/- 0.3 mg/dl after one month co-administration with cyclosporine. The magnitude of creatinine elevation was not correlated with that of change in diclofenac exposure, suggesting the pharmacokinetic interaction per se may not additionally contribute to the effect on renal function resulting from this drug combination. During longterm treatment with both medications, prospectively collected safety data indicated that renal function could be stabilized when drug doses were individually titrated in response to serial clinical and laboratory evaluations. The overall pattern of adverse events and laboratory abnormalities in the study population were similar to those reported in patients with RA treated with other nonsteroidal antiinflammatory agents and concomitant cyclosporine. CONCLUSION: Diclofenac can be safely combined with cyclosporine in the management of RA when appropriate clinical monitoring and dose titrations are performed. Due to the pharmacokinetic interaction that increases diclofenac systemic exposure, it would be prudent to start combination therapy with diclofenac doses at the lower end of the therapeutic dose range.

Adult↗
PubMed1995

Maternal HLA antigens and antibodies to SS-A/Ro and SS-B/La. Comparison with systemic lupus erythematosus and primary Sjögren's syndrome.

To study the maternal immunogenetics in congenital heart block (CHB), 31 mothers of affected children were HLA typed for class I and II antigens, and the results were compared with the corresponding HLA types in 900 healthy controls, in 45 mothers with systemic lupus erythematosus (SLE) and in 21 mothers with primary SS who had healthy children. An enzyme-linked immunosorbent assay was used to study the autoantibody responses to the recombinant 52 and 60 kDa SS-A/Ro, and 48 kDa SS-B/La proteins, and to the affinity-purified SS-A/Ro and SS-B/La antigens. Mothers of children with CHB had HLA B8 and DR3 significantly more often than healthy controls [71 vs 10%; relative risk (RR) 9.8, P < 0.00001 and 74 vs 23%; RR9.8, P < 0.001, respectively]. HLA B35 was protective (RR 0.1, P = 0.0029). Compared to controls with SLE, mothers of children with CHB were more often HLA DR3 and DQ2 positive (RR 4.1, P = 0.0057 and RR 3.1, P = 0.031, respectively), and compared to controls with primary SS less often HLA B15 positive (RR 0.1, P = 0.010). In general, the HLA antigen profile in mothers of children with CHB was more closely related to primary SS than to SLE. Levels of antibodies to all three SS-A/Ro antigens were significantly higher in mothers of children with CHB than in controls with SLE and primary SS (P = 0.0001-0.0014). With regard to SS-B/La, the autoantibody responses were similar (P = 0.32-0.66).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Prevalence of antikeratin antibodies in Greek patients with rheumatoid arthritis. A clinical, serologic, and immunogenetic study.

OBJECTIVE: The presence of antikeratin antibodies (AKA) has been associated with rheumatoid arthritis (RA) in patients from north and central Europe. Our aim was to investigate the prevalence of AKA in Greek patients with RA. METHODS: One hundred and twenty two sera of Greek patients with RA were tested for the presence of AKA by an indirect immunofluorescence technique, and HLA-DR typing was performed by restriction fragment length polymorphism. RESULTS: Nineteen of 122 (16%) Greek patients with RA were positive for AKA. The percentage of AKA in Greek patients with RA is lower than described previously. These antibodies correlated with a male preponderance (p < 0.01) and were associated with the presence of rheumatoid factor (RF) (p < 0.05) and with HLA-DR1 antigen (p < 0.05). CONCLUSION: Our results suggest that AKA are present frequently in Greek patients with RA. Their presence was found to be associated with RF and HLA-DR1 antigen. This emphasizes the different clinical expression of RA in Greece.

Adult↗
PubMed1994

Marker antibodies of rheumatoid arthritis: diagnostic and pathogenetic implications.

Rheumatoid arthritis (RA) is associated with several autoantibodies specific enough to serve as diagnostic and prognostic markers. These include rheumatoid factor (RF), antikeratin antibody (AKA), antiperinuclear factor (APF), and anti-RA33. The first three, and possibly also anti-RA33, may precede the onset of clinical RA. The prevalence of positive test reactions depends on the period between taking the specimen and onset of disease; when the period is short, the prevalence is nearly the same as in established disease. Thus, RA has a long asymptomatic period with broadening immunological activity. The assays for AKA and APF (and possibly also for anti-RA33), compared with RF testing, yielded greater specificity rather than the ability to define any subgroup with particularly severe disease. Used together, the above marker antibodies may form a new and more enlightened basis for defining seropositive RA. It is commonly believed that genetically mediated immune response plays an important role in the initiation of RA. However, the role of the major histocompatibility complex antigens may be in modulation of the inflammatory reaction in a later phase.

Antibodies, Antinuclear↗