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Biomedical subjects

M Hakala

Publications and source records attributed to M Hakala.

At least 73 records · Page 4Linked to original sources
PubMed1995

Identification of COL2A1 gene mutations in patients with chondrodysplasias and familial osteoarthritis.

OBJECTIVE: To use a recently developed procedure for analysis of blood leukocyte DNA to detect mutations in the gene for type II procollagen (COL2A1) in patients with cartilage diseases ranging from early-onset familial osteoarthritis (OA) to lethal chondrodysplasias. METHODS: The technique of denaturing gradient gel electrophoresis was used to scan polymerase chain reaction (PCR) products from 45 exons and exon-flanking sequences of the COL2A1 gene in more than 70 patients with cartilage diseases whose severity ranged from mild to lethal. PCR products with abnormal migrations were then sequenced. RESULTS: Among the 3 patients with lethal hypochondrogenesis who were analyzed, all 3 were found to have a mutation in the COL2A1 gene. Among 17 patients with spondyloepiphyseal or spondyloepimetaphyseal dysplasia, 2 well-defined and 2 probable mutations were found. Among 15 patients with the Wagner-Stickler syndrome, 2 well-defined and 2 probable mutations were found. Among 45 patients with early-onset familial OA, 1 probable mutation was found. CONCLUSION: Using the procedure developed for analysis of the COL2A1 gene, mutations were detected in > 20% of patients with chondrodysplasias and up to 2% of patients with early-onset familial OA. However, these percentages are only minimal estimates because all possible mutations in the gene cannot be detected with this procedure.

Cartilage, Articular↗
PubMed1995

Application of markers of collagen metabolism in serum and synovial fluid for assessment of disease process in patients with rheumatoid arthritis.

OBJECTIVE: To assess the potential of markers of collagen metabolism to reflect disease processes in rheumatoid arthritis (RA). METHODS: Serum (S) and synovial fluid (SF) from 59 patients with RA, and a knee joint effusion and serum from 90 control subjects were studied with radioimmunoassays for the aminoterminal propeptides of type I and type III procollagens (PINP and PIIINP, respectively). The breakdown of type I collagen was quantified with a radioimmunoassay for the cross linked carboxyterminal telopeptide of type I collagen (ICTP). RESULTS: About 50% of the patients had increased S-ICTP and S-PIIINP values, whereas S-PINP was increased in only 20% of the patients. The mean SF:S ratios of these markers varied between 4 (for ICTP) and 340 (for PIIINP), indicating that markers of collagen metabolism are formed locally and then released into the circulation. SF-PINP and SF-PIIINP correlated with each other (rs = 0.86, p < 0.001) and with SF-ICTP (rs = 0.69, p < 0.001, and rs = 0.65, p < 0.001, respectively). SF-ICTP was clearly related to radiographic findings in the corresponding knee joint, patients with gross bone deformation having the greatest SF-ICTP concentrations. S-ICTP and S-PIIINP also correlated with conventional markers of disease activity, such as C reactive protein and joint swelling score. CONCLUSION: Markers of collagen metabolism both in serum and synovial fluid can be measured to provide an assessment of disease process in patients with RA. ICTP and PIIINP are the most informative.

Adult↗
PubMed1995

Relationship of rheumatoid factor to lung diffusion capacity in smoking and non-smoking patients with rheumatoid arthritis.

We studied the relationship of serum rheumatoid factor (RF) and certain other variables to lung diffusion capacity for carbon monoxide (DLCO) in patients with rheumatoid arthritis (RA). In non-smoking patients none of the examined variables correlated significantly to DLCO whereas in smokers RF showed a significant (p < 0.01) negative correlation in this respect. These results indicate that smoking in connection with RF may contribute to reduced DLCO in RA patients.

Adult↗
PubMed1994

Type I collagen degradation product in serum of patients with early rheumatoid arthritis: relationship to disease activity and radiological progression in a 3-year follow-up.

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.

Adult↗
PubMed1994

Prevalence of cervical spine subluxations and dislocations in a community-based rheumatoid arthritis population.

The prevalence of rheumatoid cervical spine subluxations was studied by plain radiography in a population of 13,000 adults with 98 out of 103 detected cases of rheumatoid arthritis. Anterior atlantoaxial subluxation (AAS) of 4 mm or more was found in 33% of the cases and vertical dislocation in 14% or 27% depending on the diagnostic method. Lateral, posterior and subaxial subluxations were found in 14%, 2% and 21% respectively. These figures agree with former findings in clinical populations. One patient had been operated on for subaxial subluxation. Anterior AAS of 9 mm or more was found in four cases, subaxial subluxation of more than 4 mm in one case and a combination of anterior AAS of 6-9 mm and vertical dislocation in six cases. If these limits are taken as indications for surgery, as recommended earlier, about 10% of the RA patients should be operated, an unrealistic figure. It is concluded that intolerable pain or cervical myelopathy, and not the plain radiological findings alone, are indications for surgery. Most cases are treated by conservative methods.

Aged↗
PubMed1994

Prognostic significance of synovial fluid analysis in estimating the efficacy of intra-articular corticosteroid injection in patients with spondylarthropathy.

The predictive value of synovial fluid (SF) analysis and some other variables for the efficacy of intra-articular corticosteroid therapy of knee joints in 20 patients with spondylarthropathy and hydropsy in a knee joint was estimated in a prospective study. The knee joints were initially aspirated and 30 mg triamcinolone hexacetonide injected intra-articularly. The tenderness scores and the circumferences of the knee joints were measured at the start and after the two months follow up period. Between the patients with and without improvement in tenderness scores of the knee joints SF protein (p = 0.021), SF lactate (p = 0.033), SF IgG (p = 0.018) and SF IgM (p = 0.047) differed significantly, all being lower in patients with improved tenderness scores. There were no significant differences in the variables between patients with at least 2 centimetres decrease of knee joint difference and those with less during follow up.

Adrenal Cortex Hormones↗
PubMed1994

Increased type I collagen degradation in early rheumatoid arthritis.

OBJECTIVE: To evaluate the serum concentration of the mature, crosslinked carboxy terminal telopeptide of type I collagen (ICTP) in patients with early onset rheumatoid arthritis (RA) and to assess its correlation with clinically relevant features of the disease. METHODS: The serum ICTP concentration was measured in 99 adult patients with RA with a duration of disease less than one year. The main clinical outcome measures were joint count, modified Lansbury index, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Larsen index and number of erosions in peripheral joints. RESULTS: There was a strong positive correlation (p < 0.001) between the serum ICTP concentration and the Lansbury joint index and a weaker but still significant correlation (p < 0.01) between the serum ICTP concentration and the number of eroded hand and foot joints. CONCLUSION: Serum ICTP may have value as a marker of tissue destruction in patients with early RA.

Adolescent↗
PubMed1994

More evidence from a community based series of better outcome in rheumatoid arthritis. Data on the effect of multidisciplinary care on the retention of functional ability.

OBJECTIVE: To examine the severity of rheumatoid arthritis (RA), as defined by the American Rheumatism Association (ARA) 1987 revised criteria, at the population level. METHODS: The level of functional disability of the 103 patients with RA who represented practically all subjects with RA in a rural community of 13,000 adult inhabitants was assessed by the ARA Functional Classification and the Health Assessment Questionnaire (HAQ). RESULTS: Only one of the 103 patients was bedridden (ARA Class IV). According to the HAQ Functional Disability Index (FDI) two thirds of the patients had mild or at most moderate disability. Overall, less than 10% of the patients in the community were severely disabled. CONCLUSION: The level of disability in our series is lower than that reported earlier in populations with RA. These patients were treated aggressively with a median interval of one year from the first joint symptoms to the start of disease modifying antirheumatic drugs and had a median number of 2 orthopedic operations. How these interventions influenced the result cannot be accurately assessed on the basis of our cross sectional study protocol. However, high grade impairment due to destruction of large joints of lower limbs was in most instances compensated by total joint replacement surgery, performed in 20% of the cases in the series. This may partly explain the low prevalence of totally disabled patients with severe restriction in mobility in this population.

Adult↗
PubMed1994

Joint impairment is strongly correlated with disability measured by self-report questionnaires. Functional status assessment of individuals with rheumatoid arthritis in a population based series.

OBJECTIVE: To determine how well self-report functional ability reflects the impairment due to the arthritic process in rheumatoid arthritis (RA) and how much it is affected by other factors of health status. METHODS: We examined the relationships between self-report measures such as the Health Assessment Questionnaire (HAQ) and Arthritis Impact Measurement Scales (AIMS) and measures of impairment such as the Keitel function test (KFT), which is intended to reflect the degree of functional limitation of the joints, grip strength and radiological destruction as well as anxiety and depression in a population-based series of RA. RESULTS: First, the HAQ and AIMS had a high correlation coefficient (r = 0.89, p < 0.0001). Second, the above measures of impairment were more significant predictors of self-report functional measures than, for example, mental health perceptions. The AIMS scales also correlated well with the corresponding physical function of the KFT. CONCLUSION: Patients' self-report functional ability in RA reflects their physical impairment due to the arthritic joint disease and is less influenced by other factors such as emotional adjustment.

Aged↗
PubMed1993

Rheumatoid arthritis as a cause of cardiac compression. Favourable long-term outcome of pericardiectomy.

In order to clarify the significance of rheumatoid arthritis (RA) as a cause of cardiac compression, we scrutinized pericardiectomy files of 47 patients over a ten-year period at two university hospitals in Finland. Five patients with RA were found. All the patients with RA were men with seropositive disease and subcutaneous rheumatoid nodules. Two of the patients had pulmonary fibrosis, one had cutaneous vasculitis and three had had rheumatoid pleurisy. There was a mean delay of 10 months from the first cardiac symptom to the diagnosis of cardiac compression, the most common misdiagnosis being primarily a liver disease. On the basis of clinical and operative data, four out of the five patients had constrictive pericarditis and one had an effusive-constrictive form of the disease. The histopathological findings in all cases were consistent with chronic fibrosing pericarditis. A follow-up of seven to seventeen years of four patients has not revealed any signs of recurrent pericardial disease. Our results demonstrate that RA is an important aetiological factor for cardiac compression. The long-term outcome of this manifestation seems to be good after pericardiectomy.

Adult↗
PubMed1993

Increased type I collagen degradation correlates with disease severity in rheumatoid arthritis.

OBJECTIVES: To assess the extent and clinical significance of type I collagen degradation in rheumatoid arthritis (RA). METHODS: Serum samples from 90 consecutive patients with RA from a cross-sectional population based study and 90 age- and sex-matched controls were analysed with the new assay of cross-linked carboxyterminal telopeptide of type I collagen (ICTP). RESULTS: Patients with RA had significantly higher concentrations of ICTP than the controls. ICTP correlated strongly with measures of impairment in RA, such as the erosive state of joint disease (ES) (r = 0.57, p < 0.001) and Keitel function test (KFT) (r = 0.49, p < 0.001), and more weakly with various disease activity markers. When erythrocyte sedimentation rate (ESR), ES or KFT were used as indicators of disease severity among the patients with disease duration over five years, ICTP distinguished the more serious RA from milder cases. CONCLUSIONS: Elevated serum concentrations of ICTP are common in RA and are associated with signs of aggressive disease.

Adult↗
PubMed1993

More evidence of distinctive features of mixed connective tissue disease.

A comparison of clinical, immunological and HLA-D region antigen features was made between 22 patients with mixed connective tissue disease (MCTD) and 118 patients with systemic lupus erythematosus (SLE), scleroderma or primary Sjögren's syndrome. The MCTD patients had hypergammaglobulinemia more often than did those with SLE and scleroderma, but had less skin ulceration, serositis, nephritis, central nervous system disease and hypocomplementemia than the SLE patients. The frequencies of HLA-DR4 and its Dw4 subtype were significantly increased in MCTD as compared with both the other patient groups and healthy controls. Anti-RNP antibodies and the clinical characteristics together seem to illustrate a disease syndrome which is clinically and genetically distinct and fits with the prevailing concept of MCTD.

Adult↗
PubMed1993

The ARA 1987 revised criteria select patients with clinical rheumatoid arthritis from a population based cohort of subjects with chronic rheumatic diseases registered for drug reimbursement.

We tested the traditional format of the American Rheumatism Association (ARA) 1987 revised criteria for the classification of rheumatoid arthritis (RA) in a cohort of 220 subjects with drug reimbursement for chronic rheumatic diseases extracted from the National Sickness Insurance Register, in a community of 18,000 people in Finland. One hundred and nine of the 193 who consented to the study both met the new ARA criteria for RA and had disease onset after 16 years of age, giving a cumulative prevalence of 0.8% in the population of 13,300 over 16 years. The disease of 6 of them, however, fulfilled the criteria and clinical picture of some other rheumatic disease. Thus 103 patients had RA as the only diagnosis. The female:male ratio in the 103 patients was 1.7:1. Ninety-one (88%) had seropositivity at some time in their disease and 99 (96%) had erosive joint disease. In most instances the 12 seronegatives had either mild or nontypical RA and only one of them was male. The 103 patients who met the new ARA criteria had significantly more interventions, such as hospitalization, drug treatment and orthopedic surgery, than the subjects (n = 42) who despite a clinician's primary diagnosis of RA did not fulfill the criteria. Thus the new ARA criteria distinguish clinical and severe cases of RA from nonclinical or non-RA cases when applied to a population based cohort of subjects with chronic rheumatic diseases registered for drug reimbursement.

Adolescent↗
PubMed1992

Predictive value of synovial fluid analysis in estimating the efficacy of intra-articular corticosteroid injections in patients with rheumatoid arthritis.

The predictive relevance of synovial fluid analysis and some other variables for the efficacy of intra-articular corticosteroid injections in 30 patients with rheumatoid arthritis and hydropsy in a knee joint was evaluated in a prospective study. At the onset of the study, the knee joints were aspirated and 30 mg triamcinolone hexacetonide injected intra-articularly. The circumferences and the tenderness scores of the knee joints were measured at onset, after two months, and at the end of the six months' follow up. Of the variables studied, synovial fluid C4, percentage of synovial fluid polymorphonuclear leucocytes, blood haemoglobin, and serum C3 correlated significantly with the decrease in knee joint circumference after two months, whereas only the percentage of synovial fluid polymorphonuclear leucocytes correlated significantly after six months. Between the patients with and without improvement in the tenderness scores of the knee joints, only serum IgM differed at the examination after two months; this was higher in patients whose scores showed no improvement.

Adult↗
PubMed1992

No association between rheumatoid arthritis and insulin dependent diabetes mellitus: an epidemiologic and immunogenetic study.

To acquire more information on the controversial question of a possible association between rheumatoid arthritis (RA) and insulin dependent diabetes mellitus we searched for insulin dependent diabetes mellitus among patients hospitalized due to RA in 2 rheumatism hospitals in Finland. Nine subjects with insulin dependent diabetes mellitus were found among an annual number of 1460 patients admitted to one of the hospitals due to RA. These figures give a frequency of insulin dependent diabetes mellitus in patients with RA of 0.6% (95% confidence interval 0.2-1.0%), which does not exceed the prevalence of insulin dependent diabetes mellitus among the middle aged population of Finland in general (0.5-0.6%). Accordingly, no overrepresentation of homozygosity for HLA-DR4 was found among the total number of 25 patients with RA as well as insulin dependent diabetes mellitus, though the opposite might be expected as these diseases have a common DR4 association--RA with DR4 and DR1 and insulin dependent diabetes mellitus with DR4 and DR3. Instead, an increased frequency of DR1 (p less than 0.0002) and the antigen combination DR1/4 (p less than 0.01) was found in the subjects with both RA and insulin dependent diabetes mellitus compared with the subjects with insulin dependent diabetes mellitus alone.

Adult↗