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C Haire

Publications and source records attributed to C Haire.

4 recordsLinked to original sources

HLA-DRB1 typing in rheumatoid arthritis: predicting response to specific treatments.

OBJECTIVE: To determine the predictive value of shared epitope alleles for response to treatment in patients with rheumatoid arthritis. METHODS: Patients from our previously published triple DMARD study were tested for the presence of shared epitope alleles (DRB1 *0401, 0404/0408, 0405, 0101, 1001, and 1402). Patients who were shared epitope positive were then compared with those who were negative to see if there was a differential effect on therapeutic response. RESULTS: Shared epitope positive patients were much more likely to achieve a 50% response if treated with methotrexate-sulphasalazine-hydroxychloroquine compared with methotrexate alone (94% responders versus 32%, p < 0.0001). In contrast shared epitope negative patients did equally well regardless of treatment (88% responders for methotrexate-sulphasalazine-hydroxychloroquine versus 83% for methotrexate). Additionally, a trend toward an inverse relation of the gene dose was seen for response to methotrexate treatment (p = 0.05). CONCLUSIONS: These data suggest that determining shared epitope status may provide clinical information useful in selecting among treatment options.

Adult↗

Efficacy of triple DMARD therapy in patients with RA with suboptimal response to methotrexate.

Rheumatoid arthritis (RA) has a profound effect on patients, producing significant morbidity and in some cases mortality. Because of this, most rheumatologists are moving to disease modifying antirheumatic drug (DMARD) therapy earlier in the course of RA. Methotrexate (MTX) has become the initial DMARD of choice for most rheumatologists. Unfortunately, treatment of RA with a single DMARD, including MTX, often results in a suboptimal response. Therefore, most rheumatologists are now using combinations of DMARD to treat patients with RA who have had incomplete responses to single DMARD therapy. The Rheumatoid Arthritis Investigational Network (RAIN) reported the results of a double blind, controlled comparison of triple drug therapy (MTX-sulfasalazine-hydroxychloroquine) against MTX alone, and against the combination of hydroxychloroquine and sulfasalazine. Twenty-eight patients who had suboptimal responses to MTX or the combination of sulfasalazine and hydroxychloroquine were then treated with triple therapy in an open label study. Fourteen had previously failed MTX therapy, and 14 had previously failed combination therapy with sulfasalazine and hydroxychloroquine. Both groups had statistically significant improvements in sedimentation rates, morning stiffness, swollen joint scores, tender joint scores, patient global status assessment, and physician global status assessment. Statistical significance was reached for all these variables for patients in both groups, but improvement was greater for the patients in the sulfasalazine-hydroxychloroquine group. Patients with RA who have had suboptimal responses to MTX, or to the combination of sulfasalazine-hydroxychloroquine, show both statistical and clinically significant improvement in multiple clinical variables when treated with the combination of MTX 17.5 mg/week, sulfasalazine 500 mg bid, and hydroxychloroquine 200 mg bid.

Adult↗

LY146032 in a hamster model of Staphylococcus aureus pneumonia--effect on in vivo clearance and mortality and in vitro opsonophagocytic killing.

The effect of the new peptolide LY146032 (LY) was studied in a hamster model of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. In vivo, after infection with one of two well-encapsulated strains of MRSA, A83 and A116 (type 8 and type 5), LY was protective only in A116 pneumonia. An in vitro assay of the effect of subinhibitory concentrations of LY on opsonophagocytic killing by pulmonary phagocytes demonstrated marked enhancement of killing of A116 (92.6 and 63.8% kill with 1/10 MIC and 1/50 MIC LY; no kill in the absence of LY). This effect was dependent on the presence of fresh serum. LY in subinhibitory concentrations produces a surface effect that may allow complement binding and activation and subsequent phagocytosis and killing to take place. The opsonizing effect of subinhibitory concentrations of LY was not demonstrable for the A83 strain. Differences in capsular types may be determinants of response to therapy of MRSA infections.

Animals↗