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W Neal Roberts

Publications and source records attributed to W Neal Roberts.

4 recordsLinked to original sources
PubMed2006

Treatment of skeletal Erdheim-Chester disease with zoledronic acid: case report and proposed mechanisms of action.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by tissue infiltration of lipid-laden macrophages, multinucleated giant cells, and inflammatory infiltrate of lymphocytes and histiocytes. The disease typically involves long bone, but may also affect the central nervous system, the orbit, retroperitoneal organs, and the lungs. Patients with visceral involvement tend to have poorer outcome. There is no proven effective treatment for ECD to date. However, recent data suggested the potential use of bisphosphonates for the treatment of this rare disease. Here we report a case of biopsy-proven skeletal ECD, who received treatment with zoledronic acid, an aminobisphosphonate, with remarkable clinical improvement. We also discuss possible mechanisms of action of bisphosphonates in this disorder, especially their roles in inhibition of inflammatory cytokines and macrophage infiltration.

Bone Density Conservation Agents↗
PubMed2002

Hydroxychloroquine concentration-response relationships in patients with rheumatoid arthritis.

OBJECTIVE: A dose-response relationship for hydroxychloroquine (HCQ), in terms of the proportion of patients achieving the Paulus 20% criteria for improvement, had previously been observed in patients with rheumatoid arthritis (RA) receiving a 6-week loading regimen of 400, 800, or 1,200 mg HCQ daily. This present retrospective analysis was performed to investigate possible relationships between the blood HCQ and HCQ-metabolite concentrations and measures of efficacy and toxicity. In addition, we sought to ascertain whether further investigation of HCQ/HCQ-metabolite levels might lead to testing of one of these substances as a new antirheumatic drug. METHODS: Patients with active RA (n = 212) began a 6-week, double-blind trial comparing 3 different doses of HCQ at 400, 800, or 1,200 mg/day, followed by 18 weeks of open-label HCQ treatment at 400 mg/day. Patients were repeatedly evaluated for treatment efficacy and toxicity. Blood samples were available from 123 patients for analysis of HCQ, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ) levels using high-performance liquid chromatography. Achievement of the modified Paulus 20% improvement criteria for response in RA was used as the primary efficacy parameter. Spontaneously reported adverse events were categorized and analyzed as toxicity outcome variables. The relationship between response (efficacy and toxicity) and drug levels was evaluated using logistic regression analysis. RESULTS: The subset of patients with blood concentration data was equivalent to the larger study population in all demographic and outcome characteristics. The mean HCQ, DHCQ, and DCQ elimination half-lives were 123, 161, and 180 hours, respectively. There was a positive correlation between the Paulus 20% improvement criteria response and blood DHCQ concentrations during weeks 1-6 (P < 0.001). A potential relationship between ocular adverse events and BDCQ levels was found (P = 0.036). Logistic regression analysis of adverse events data showed that adverse gastrointestinal events were associated with higher HCQ levels (P = 0.001-0.021) during weeks 1, 2, and 3. CONCLUSION: There is a weak, but predictable, relationship between blood DHCQ concentrations and efficacy of treatment with HCQ. In addition, there is an association between gastrointestinal adverse events and elevated blood HCQ concentrations. Further investigation of these relationships is warranted to see if DHCQ may be introduced as a new antirheumatic drug.

Adult↗
PubMed2002

Another look at synovial fluid leukocytosis and infection.

Synovial fluid white blood cell counts are considered to be useful in diagnosing infectious arthritis, however, considerable overlap exists between infectious and noninfectious types of inflammatory arthritis. We undertook this review of synovial fluid studies at our institution to better define this degree of overlap and characterize the features of infectious arthritis in relationship to synovial fluid white cell counts. The records of 202 consecutive patients with synovial fluid white blood cell counts >2000/mm were reviewed. Infectious arthritis was diagnosed in 77% (10/13) of patients with counts >100,000, 47% (8/17) in the 50,000-100,000 range, and 5% (9/172) with counts <50,000. Crystal-induced arthritis and rheumatoid arthritis made up 81% of patients in the 15,000-50,000 range. Overall, 10 of 27 (37%) cases of infectious arthritis had white cell counts >100,000, and 18 of 27 (67%) had counts >50,000. A majority of these infections (14/18) were related to Staphylococcus aureus, while 5 of 7 infections associated with counts <20,000 were associated with atypical organisms. This study confirms that a majority of patients with very high synovial fluid white blood cell counts have infectious arthritis, and that the likelihood of infection is markedly reduced, but certainly not excluded, below this level. The presence of atypical infections in a small percentage of patients with low counts emphasizes the importance of clinical judgment in evaluating all patients with inflammatory arthritis, regardless of synovial fluid white cell counts.

Journal Article↗