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Biomedical subjects

T L Moore

Publications and source records attributed to T L Moore.

142 records · Page 8Linked to original sources
PubMedDate not supplied

Screening for uveitis in juvenile rheumatoid arthritis.

BACKGROUND: Uveitis associated with juvenile rheumatoid arthritis (JRA) is an important cause of visual impairment in children. Because uveitis is often asymptomatic in this age group, frequent ophthalmologic screening examinations are recommended. Recent reports have found a decrease in the prevalence and severity of uveitis in JRA when compared to older data. METHODS: The charts of 52 consecutive patients with JRA seen over a 30-month period were retrospectively reviewed. RESULTS: Eye examination identified uveitis in five (12%) patients. All patients with uveitis were female, ANA positive, and had pauciarticular-onset arthritis. Three patients had the onset of uveitis before the age of 2. All patients have maintained good visual acuity and have not developed serious sight-threatening ocular complications over the follow-up period. CONCLUSIONS: Although the prevalence and severity of JRA-associated uveitis may be decreasing, we strongly recommend continued strict adherence to the current screening guidelines.

Antibodies, Antinuclear↗
PubMedDate not supplied

Correlation of antiperinuclear factor with antibodies to streptococcal cell-wall peptidoglycan-polysaccharide polymers and rheumatoid factor.

Antiperinuclear factor (APF) has been noted in most seropositive rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) patients. The nature of the antigen is unknown; however, there are some suggestions that it might be a glycoprotein or proteoglycan. We studied the correlation of APF with antiproteoglycan antibodies and the reactivity of IgM-rheumatoid factor (RF) with the perinuclear antigen. Ten serum samples were separated to IgG, IgM, and IgM-RF enriched fractions. In seven samples, APF was found in the IgG fraction. Only 4 had APF in their IgM rheumatoid factor (RF)-containing fraction. In two of these, APF activity was present solely in the IgM RF fraction and was inhibited by pre-incubation with IgG. Fifty-five JRA patients' sera were also tested for the presence of antibodies to Streptococcal cell wall peptidoglycan-polysaccharide polymers (PG-PSP). 76% of the APF-positive sera were anti-PG-PSP positive and 59% of the APF-negative sera were also anti-PG-PSP negative. Furthermore, 75% of the APF-positive sera lost their APF activity following adsorption to Streptococcal cell wall PG-PSP. Our results show that in JRA sera APF are polyclonal antibodies of both the IgG and IgM classes. Although the presence of APF correlates with RF positivity, and they sometimes may cross-react, many IgM RF-containing fractions do not show APF activity. However, the presence of APF does correlate with anti-PG-PSP positivity and the data suggest cross-reactivity between these two antibodies. This implies antigenic similarity between Streptococcal cell wall PG-PSP and the perinuclear antigen.

Antibodies↗
PubMedDate not supplied

Diflunisal versus naproxen in the management of rheumatoid arthritis.

Diflunisal (500 mg orally, twice daily) and naproxen (375 mg orally, twice daily) were compared for efficacy and tolerability in a 12-week open-label study in 33 patients with active rheumatoid arthritis (RA). Both drugs resulted in marked reduction in the number of swollen, tender, and painful joints and comparable improvement in patients' assessment of disease activity and pain. There were no significant differences between the two medications in the measured indices of disease activity. No adverse experiences were reported by patients in either treatment group. The results indicate that both diflunisal and naproxen were equally effective and that both agents are generally well tolerated in this group of patients with RA.

Adult↗
PubMedDate not supplied

Longitudinal study of the presence of hidden 19S IgM rheumatoid factor in juvenile rheumatoid arthritis.

Complement-fixing hidden 19S IgM rheumatoid factor (RF), i.e., 19S IgM RF that can be detected in the IgM-containing fraction by the hemolytic assay after separation of the serum by acid gel filtration, was evaluated serially (3 or more evaluations) over a 4-year period in 26 children with juvenile rheumatoid arthritis (JRA) correlating its presence with disease activity. Six children with continually active disease had consistently elevated hidden RF titers (26 evaluations), and the titers of 4 children with inactive disease remained insignificant (12 evaluations). Sixteen children had disease with variable activity over this period. Of these, 11 (43 evaluations) demonstrated positive correlation between disease activity and hidden RF titers. Five patients (8/20 evaluations) did not show correlation of disease activity with hidden RF titers. Thus, the presence of hidden RF correlated with disease activity in 93 of 101 evaluations. When hidden RF titers and the erythrocyte sedimentation rate were determined simultaneously on 40 occasions, the presence of hidden 19S IgM RF correlated significantly better (p less than 0.001) with disease activity.

Arthritis, Juvenile↗
PubMedDate not supplied

Immune complexes in juvenile rheumatoid arthritis: a comparison of four methods.

Fifty-three children with juvenile rheumatoid arthritis (JRA) were tested for immune complexes (IC) by 4 different methods, Clq solid-phase assay (ClqSPA), 2% polyethylene glycol precipitation assay (PEGPA), Raji cell assay (RCA), and the conglutinin assay (KA). Seventy-nine % of JRA patients demonstrated elevated IC levels by at least 1 method. Fifty-eight % of the JRA patients have elevated levels of IC by ClqSPA, 50% by the RCA, 37% by the KA, but 0% by the PEGPA. Seventy-four % of patients with polyarticular-onset, 88% of pauciarticular-onset, and 80% of systemic-onset JRA showed elevated levels of IC by at least 1 method. In the polyarticular-onset group, both in the rheumatoid factor (RF) positive (100%) and RF negative (64%) patients, and in the systemic-onset group (60%) the most elevated levels were demonstrated by the ClqSPA. The most elevated levels were found in the pauciarticular-onset type (69%) by the RCA. The presence of elevated levels of IC by the KA correlated with the presence of RF (p less than 0.01), hidden RF (p less than 0.05), and antinuclear antibodies (p less than 0.005). Elevated levels of IC detected by the ClqSPA correlated with the presence of RF (p less than 0.01), hidden RF (p less than 0.05), and active disease (p less than 0.01).

Antigen-Antibody Complex↗
PubMedDate not supplied

Localized scleroderma and idiopathic thrombocytopenia.

Two patients with localized scleroderma who developed thrombocytopenic purpura are reported. In both patients the thrombocytopenia improved after prednisone therapy, and has not recurred in 5 and 8 yr of subsequent observation without steroids. Both patients had a positive antinuclear antibody (ANA) test and 1 had a positive assay for immune complexes by the Clq solid phase radioimmunoassay. Non-immune causes for the lowered platelets were not found. This possible association may add a new, potentially life-threatening dimension to localized scleroderma.

Adolescent↗
PubMedDate not supplied

Chlorambucil in the treatment of iridocyclitis in juvenile rheumatoid arthritis.

A patient with chronic, progressive, iridocyclitis secondary to pauciarticular juvenile rheumatoid arthritis (JRA) is described. The patient's iridocyclitis was unresponsive to topical, systemic, and subtenon injections of corticosteroids, but did respond to low doses of chlorambucil. The use of immunosuppressives may be indicated in severe, unresponsive iridocyclitis secondary to JRA.

Arthritis, Juvenile↗
PubMedDate not supplied

Ehlers-Danlos syndrome presenting as rheumatic manifestations in the child.

Nine patients with Ehlers-Danlos syndrome (EDS) presented with joint complaints. This represented 5% of the new pediatric arthritis patients seen over a 6-month period. All 9 patients had a history of double-jointedness, and 7 had arthralgias associated with increased physical activity. On physical examination all had hypermobile joints, 7 had joint tenderness, but none had joint swelling. Based on the presence of other features including hyperextensible skin, widened scars, and cardiac clicks and murmurs, 8 were categorized as EDS Type II and 1 as EDS Type III. It posed a significant problem because the diagnosis had not been previously entertained before consultation and erroneous diagnosis had been made. Therefore, EDS should be included in the differential diagnosis of polyarthralgia in the child.

Adolescent↗
PubMedDate not supplied

Hidden 19S IgM rheumatoid factor in synovial fluid.

Synovial fluid (SF) of 16 adult patients with rheumatoid arthritis (RA) and 9 children with juvenile rheumatoid arthritis (JRA) was investigated for the presence of hidden 19S IgM rheumatoid factor (RF). SF was incubated with 500 IU hyaluronidase/g of SF, dialyzed against acetate buffers at decreasing pH, centrifuged and subjected to chromatography on a Sephadex G-200 column. The resulting IgM-containing fraction of SF from 5 seropositive patients (3 adult RA, 2 JRA patients) demonstrated RF activity by the complement-dependent hemolytic assay. Hidden 19S IgM RF was not found in the IgM-containing fractions of SF from 13 adult seronegative RA patients. Hidden 19S IgM RF was shown in the IgM-containing fraction of SF in 4 of 7 children with seronegative JRA.

Adult↗
PubMedDate not supplied

Immune complexes from sera of patients with juvenile rheumatoid arthritis reveal novel 40 and 60 kd bands.

OBJECTIVE: Immune complexes (IC) have been detected in the majority of sera of patients with juvenile rheumatoid arthritis (JRA). Our aim was to determine the possible constituents of these IC. METHODS: One hundred and four sera from patients with JRA were separated on a Sepharose 4B column to which were bound F(ab')2 fragments of goat anti-human IgM antibody to separate IgM-containing IC. The column was sequentially eluted with 1 M ammonia and 0.1 M glycine-HCl buffer, pH 3. The eluted material was treated with sodium dodecyl sulfate (SDS) and simultaneously reduced with 2-mercaptoethanol. Individual components were then separated by SDS-gradient polyaclylamide gel electrophoresis and were transferred to nitrocellulose by Western blotting. The nitrocellulose strips were overlaid with the patient's own serum and developed with specific antiserum to human IgM and IgG. RESULTS: Four bands were noted in the majority of JRA patients, including a band in the 70-80 kD area to the IgM heavy chain and in the 50 kD area to the IgG heavy chain. Additional bands specific for JRA patients' sera were noted in the 40 kD and 60 kD areas. Overall, 61 of 104 sera demonstrated all four bands; 78 showed the 40 kD band and 73 the 60 kD band. CONCLUSION: These IC were previously shown to contain IgM rheumatoid factor (RF), IgG-RF, and IgG in addition to the 40 and/or 60 kD constituents present in the isolates. Preliminary studies on these constituents suggest the possibility of the 60 kD band being the human 60 kD mitochondrial heat shock protein. Further investigations of these immune complex components may aid in the understanding of the pathophysiology of JRA.

Adolescent↗
PubMedDate not supplied

In vitro effects of methotrexate on polyamine levels in lymphocytes from rheumatoid arthritis patients.

OBJECTIVE: Several studies have documented increased levels of polyamines in rheumatoid arthritis (RA). We have suggested that one of the mechanisms of action of methotrexate (MTX) involves the inhibition of polyamine synthesis in lymphocytes. In this study, we sought to establish the inhibitory effect of MTX on polyamine synthesis and its specificity. METHODS: Polyamine levels were determined in stimulated RA lymphocytes incubated in vitro with MTX and compared to levels in lymphocytes incubated with hydrocortisone, D-penicillamine, or medium alone. Lymphocyte polyamine levels were correlated with IgM-rheumatoid factor (RF) synthesis. RESULTS: Incubation with MTX resulted in concentration-dependent decreased intracellular levels of spermidine and spermine, while putrescine levels were not affected. Addition of folinic acid or S-adenosyl-methionine (SAM) prevented this MTX-induced inhibition. Incubation with D-penicillamine or hydrocortisone had no significant effect on polyamine levels. There was a positive correlation between intracellular polyamine levels and the inhibition of IgM-RF synthesis by MTX. CONCLUSION: These data suggest that MTX inhibits the synthesis of spermidine and spermine in stimulated RA lymphocytes through inhibition of the SAM-dependent pathway. This inhibition may be related to the immune-modulating properties of MTX.

Anti-Inflammatory Agents↗
PubMedDate not supplied

Effect of treatment with methotrexate, hydroxychloroquine, and prednisone on lymphocyte polyamine levels in rheumatoid arthritis: correlation with the clinical response and rheumatoid factor synthesis.

OBJECTIVE: Polyamines are increased in activated lymphocytes, including peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis (RA), and are important in modulating immune-mediated cellular responses. In vitro studies have suggested that methotrexate (MTX) interferes with polyamine synthesis. This study evaluated the in vivo polyamine response to MTX compared to other anti-arthritic agents, and correlated it with the clinical and immunological response. METHODS: The polyamine content of PBL was determined in 14 RA patients at initiation of treatment with MTX (n = 8), hydroxychloroquine (HCQ) (n = 3), or prednisone (n = 3), and then monthly for four months. IgM rheumatoid factor (RF) synthesis by PBL in vitro was assessed and tender joints were counted monthly. RESULTS: Polyamines (spermine and spermidine) decreased by 55% at three months in the MTX group compared to 4% and 9% in the HCQ and prednisone groups, respectively (p < 0.01). However, group differences in the clinical and immunological response were not significant. In the MTX group there was a positive correlation between polyamine levels and the joint count. Such a correlation was not observed in the other groups. CONCLUSION: These data suggest that MTX interference with the polyamine pathway is not shared by prednisone and HCQ, and is associated with its beneficial effect in RA.

Adult↗
PubMedDate not supplied

Reduced levels of testosterone and dehydroepiandrosterone sulphate in the serum and synovial fluid of juvenile rheumatoid arthritis patients correlates with disease severity.

OBJECTIVE: The status of androgen levels and their significance in the pathogenesis of juvenile rheumatoid arthritis (JRA) has not been fully investigated. In the present study serum and synovial fluid (SF) from 20 JRA patients (grouped as pre-pubertal and pubertal) were analyzed for their content of testosterone, dehydroepiandrosterone (DHEA) and its sulphated conjugate DHEA-S, progesterone and 17 beta-estradiol. RESULTS: Comparison of the results from JRA patients with that of age-matched controls indicated no significant differences in progesterone and DHEA. Similarly, 17 beta-estradiol levels from the pubertal group were comparable to those of the controls; however, prepubertal patients had no detectable levels of this hormone. DHEA-S values were significantly lower in the pubertal JRA group, 1388.3 +/- 291.8 and 1663.9 +/- 354.1 nmol/l in the serum and SF, respectively (compared to 8206.6 +/- 848.12 in the serum of matching controls). These patients also presented with a much lower testosterone content in their SF than in their serum, 0.09 +/- 0.036 and 0.56 +/- 0.068 nmol/l, respectively (compared to 1.35 +/- 0.146 in the serum of corresponding controls). CONCLUSION: The data presented in this paper demonstrate for the first time an association between low androgen levels and disease in JRA patients. The significance of hypoandrogenicity with respect to the pathogenic mechanisms of arthritic disease and the possible therapeutic strategies that these imply warrants further investigation.

Adolescent↗