The value of synovial fluid analysis in the assessment of knee joint destruction in arthritis in a three year follow up study

OBJECTIVES: To assess the predictive significance of synovial fluid (SF) analysis for progressive radiological knee joint destruction in arthritis. METHODS: Altogether 55 patients with arthritis and knee joint effusion were included in the study. The diagnosis was rheumatoid arthritis (RA) for 44 of them, chronic seronegative spondylarthropathy for seven and juvenile rheumatoid arthritis for four. The mean age of the patients was 51.8 (SD 14.9, range 19-82) years, and the mean duration of disease 10.9 (SD 9.2, range 0.5-37) years. In addition to the routine laboratory tests, different markers of collagen synthesis and breakdown in serum and SF were assessed. The radiological grade of the knee joint was assessed by Larsen's method at the baseline and after a three year follow up. RESULTS: During the follow up, Larsen's grade deteriorated in 22 (40%) patients. These patients had a significantly higher median level of cross linked carboxyterminal telopeptide of type I collagen (ICTP) in SF at entry than those who had a stable index (p = 0.035). Serum ICTP did not have any predictive value for a specific joint. The median levels of total SF leucocytes (p = 0.012) and the subgroup of polymorphonuclear leucocytes (p = 0.018) were higher in the patients with a stable Larsen's index. However, the relation of SF leucocyte level to radiological progression could not be confirmed in the RA group. CONCLUSION: It is concluded that SF analysis may help in the identification of patients with inflammatory arthritis who are at risk for progressive destruction in a particular joint. A high total SF leucocyte level is not necessarily associated with a poor prognosis. Instead, a high SF ICTP level seems to reflect accelerated bone degradation.     

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.     

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.     

Increased carotid intima-media thickness in men born in east Finland: a twin study of the effects of birthplace and migration to Sweden on subclinical atherosclerosis

BACKGROUND: There is a clear east-west difference in coronary heart disease (CHD) mortality and incidence in Finland, people living in east Finland having higher CHD rate. A study of Finnish immigrants to Sweden has suggested that a long stay in Sweden would be associated with reduced CHD risk. AIM: To determine whether structural and functional markers of subclinical atherosclerosis differ between men originating from east and west Finland, and whether migration to Sweden influences subclinical atherosclerosis. METHOD: Carotid intima-media thickness (IMT) and brachial artery flow-mediated dilatation (FMD) with high-resolution ultrasound and a set of cardiovascular risk factors were measured in 76 middle-aged male twin pairs (55 pairs from east and 21 pairs from west Finland) discordant for migration to Sweden. RESULTS: Among men living in Finland, IMT was significantly higher in men originating from east Finland compared to those from west Finland (0.796 +/- 0.212 versus 0.704 +/- 0.123 mm, P = 0.02). A similar east-west difference was observed in men who had migrated to Sweden (0.766 +/- 0.220 versus 0.686 +/- 0.089 mm, P = 0.03). The east-west difference in IMT persisted after adjustment for the major traditional cardiovascular risk factors. No east-west difference was seen in FMD. Smoking, Framingham risk score and physical activity had a greater impact on IMT in men originating from east compared to west Finland. CONCLUSIONS: Men originating from east Finland, irrespective of their current residence, have a greater degree of subclinical atherosclerosis and they may be more susceptible to the impact of conventional cardiovascular risk factors than men originating from west Finland.     

Metabolism and serum binding of Ru 486 in women after various single doses*

The metabolism of RU 486 was studied in female volunteers followinga single oral administration of 100, 400, 600 or 800 ing ofRU 486. The serum concentrations of RU 486 were generally notaffected by the dose within the range examined and they stayedat micromolar concentrations during the 48 h studied. RU 486was metabolized extensively in a dose-dependent manner by two-stepdemethylation, and by hydroxyl-ation. Serum levels of the monodemethylatedmetabolite always exceeded those of RU 486. The concentrationsof the didemethylated and hydroxylated metabolites equalledor exceeded those of RU 486 when the ingested dose was 400 mgor more. Monodemethylation and hydroxylation were rapid high-capacityreactions, whereas didemethylation was a tower-capacity reaction.In each group of different dosage, positive correlations werefound between the individual mean 1-acid glycoprotein (AAG)concentrations and the peak concentration of RU 486 measuredat 1-2 h, versus the plateau concentration of RU 486 measuredat 6 h. The in-vitro studies showed that the specific serumtransport protein of RU 486, AAG, was saturated by RU 486 concentrationsexceeding 2.5 /tM. In serum at 40 nM and 2.5 /tM RU 486 concentrations,2.7% and 2.4%, respectively, of [³H]RU 486 was not protein bound.Purified AAG in phosphate buffer was able to bind [³H]RU 486in a similar manner to that of serum. Thus our results suggestthat AAG regulates in part the serum concentrations of RU 486,and RU 486 exceeding the specific serum transport capacity iseffectively metabolized.     

Proportions of immunoglobulin isotypes in paralytic poliomyelitis and after vaccination

Immunoglobulin isotype composition of poliovirus antibodies was studied by isotype-specific solid-phase radio-immunoassay (RIA) in four patients with paralytic poliomyelitis, five adults receiving live poliovirus vaccine as a booster immunization, and seven children receiving first doses of inactivated poliovirus vaccine. In paralytic poliomyelitis serum and cerebrospinal flind (CSF) poliovirus antibodies were mainly of IgG1, IgG3, and IgA isotypes. IgM antibodies were found in sera but not in CSF. Either IgG2 and IgG4 antibodies were undetectable or the titers were low. In adults who had received live trivalent poliovirus vaccine, antibodies against poliovirus type 3 were detected in IgG1 (53% of total antibodies), IgG3 (25%), IgM (9%), IgA (8%), IgG2 (3%), and IgG4 (2%) isotypes. In prevaccination and late postvaccination sera the share of IgG3 antibodies was exceptionally high (35%). In children who received inactivated poliovirus vaccine, antibodies developed in IgG1 (53–61% of total antibodies for poliovirus types 1, 2, and 3), IgG3 (12–21%), and IgM (23–33%) isotypes. Antibody levels in IgG2, IgG4, and IgA isotypes were low and observed only in a few cases. Like other viral antibodies IgG1 and IgG3 isotypes were the major IgG subclasses in poliovirus antibodies.     

Screening for mutations in the exon 26 of the apolipoprotein B gene in hypercholesterolemic finnish families by the single-strand conformation polymorphism method

To date, the only known apolipoprotein B (apo B) mutation causing hypercholesteroletnia is the apo B 3500 Arg → Gln or the familial defective apo B (FDB) mutation. This mutation has not been detected in the Finnish population. We have set up a systematic single-strand conformation polymorphism (SSCP) analysis-based screening method to search for other mutations in the exon 26 of the apo B gene in 21 Finnish hypercholesterolemic probands. The 7572-bp exon 26 covers half of the coding region of the gene including the DNA sequence coding for the putative low-density lipoprotein (LDL) receptor binding site on the apo B protein. Exon 26 was amplified as six 1190- to 1435-bp fragments, each of which was further split into three smaller 213- to 579-bp segments by restriction enzymes. These digestion products were run on nondenaturing polyacrylamide gels using at least three different electrophoretic ccnditions and autoradiographed. All previously known genetic variants in the exon 26 were detected by the SSCP method. A C→T change at nucleotide 7064, in complete association with the XbaI site, was characterized by direct sequencing. This variant did not affect the amino acid sequence of the apo B protein. The SSCP-based procedure appears suitable for systematic screening for DNA sequence changes in large coding regions. © 1994 Wiley-Liss, Inc.     

Impact of initial aggressive drug treatment with a combination of disease‐modifying antirheumatic drugs on the development of work disability in early rheumatoid arthritis: A five‐year randomized followup trial

Objective

To compare the efficacy of therapy with a combination of disease‐modifying antirheumatic drugs (DMARDs) versus therapy with a single DMARD in the prevention of work disability in patients with early rheumatoid arthritis (RA).

Methods

In the Finnish Rheumatoid Arthritis Combination Therapy trial, 195 patients with recent‐onset RA were randomly assigned to receive either combination therapy with DMARDs (sulfasalazine, methotrexate, hydroxychloroquine) plus prednisolone or single therapy with a DMARD with or without prednisolone. After 2 years, the drug treatment strategy was no longer restricted. At baseline, 162 patients (80 in the combination‐treatment group and 82 in the single‐treatment group) were still working or at least available for work. After 5 years of followup, data on all sick leave and retirement were obtained from social insurance registers or case records. The main outcome for each patient was the cumulative duration of all sick leaves and RA‐related disability pensions, divided by the observation period during which the patient was not retired because of another disease or because of age.

Results

The cumulative duration of work disability per patient‐observation year was significantly lower in those randomized to combination therapy than in those randomized to single therapy: median 12.4 days (interquartile range [IQR] 0–54) versus 32.2 days (IQR 6–293) (P = 0.008, sex‐ and age‐adjusted P = 0.009). This was mainly due to the difference in sick leaves (i.e., work disability periods ≤300 days): median 11.7 days (IQR 0–44) per patient‐observation year in those treated with combination therapy and 30.0 days (IQR 6–68) in those treated with single therapy (P = 0.002). No statistically significant difference was seen in RA‐related disability pensions.

Conclusion

Aggressive initial treatment of RA with a combination of DMARDs improves 5‐year outcome in terms of lost productivity in patients with RA of recent onset.