ABSTRACT
The purpose of this study was to compare knowledge in managing low back pain (LBP) between physical therapists and family practice physicians. Fifty-four physical therapists and 130 family practice physicians currently serving in the U.S. Air Force completed standardized examinations assessing knowledge, attitudes, the usefulness of clinical practice guidelines, and management strategies for patients with LBP. Beliefs of physical therapists and family practice physicians about LBP were compared using relative risks and independent t tests. Scores related to knowledge, attitudes, and the usefulness of clinical practice guidelines were generally similar between the groups. However, physical therapists were more likely to recommend the correct drug treatments for patients with acute LBP compared to family practice physicians (85.2% vs. 68.5%; relative risk: 1.24 [95% confidence interval: 1.06-1.46]) and believe that patient encouragement and explanation is important (75.9% vs. 56.2%; relative risk: 1.35 [95% confidence interval: 1.09-1.67]). In addition, physical therapists showed significantly greater knowledge regarding optimal management strategies for patients with LBP compared to family practice physicians. The results of this study may have implications for health policy decisions regarding the utilization of physical therapists to provide care for patients with LBP without a referral.
Subject(s)
Health Knowledge, Attitudes, Practice , Low Back Pain/therapy , Military Personnel , Physical Therapists , Physicians, Family , Adult , Aerospace Medicine , Female , Guideline Adherence , Humans , Male , Middle Aged , Practice Guidelines as Topic , United StatesABSTRACT
B cell activation factor of the TNF family (BAFF) is a potent B cell survival factor. BAFF overexpressing transgenic mice (BAFF-Tg mice) exhibit features of autoimmune disease, including B cell hyperplasia and hypergammaglobulinemia, and develop fatal nephritis with age. However, basal serum IgA levels are also elevated, suggesting that the pathology in these mice may be more complex than initially appreciated. Consistent with this, we demonstrate here that BAFF-Tg mice have mesangial deposits of IgA along with high circulating levels of polymeric IgA that is aberrantly glycosylated. Renal disease in BAFF-Tg mice was associated with IgA, because serum IgA was highly elevated in nephritic mice and BAFF-Tg mice with genetic deletion of IgA exhibited less renal pathology. The presence of commensal flora was essential for the elevated serum IgA phenotype, and, unexpectedly, commensal bacteria-reactive IgA antibodies were found in the blood. These data illustrate how excess B cell survival signaling perturbs the normal balance with the microbiota, leading to a breach in the normal mucosal-peripheral compartmentalization. Such breaches may predispose the nonmucosal system to certain immune diseases. Indeed, we found that a subset of patients with IgA nephropathy had elevated serum levels of a proliferation inducing ligand (APRIL), a cytokine related to BAFF. These parallels between BAFF-Tg mice and human IgA nephropathy may provide a new framework to explore connections between mucosal environments and renal pathology.
Subject(s)
B-Cell Activating Factor/genetics , B-Cell Activating Factor/immunology , Glomerulonephritis, IGA/etiology , Animals , Antibodies, Antinuclear/blood , Antibodies, Bacterial/blood , B-Cell Activating Factor/blood , DNA-Binding Proteins/blood , Disease Models, Animal , Female , Gene Expression , Glomerulonephritis, IGA/genetics , Glomerulonephritis, IGA/immunology , Glomerulonephritis, IGA/pathology , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Kidney/immunology , Kidney/pathology , Male , Mice , Mice, Transgenic , Transcription Factors/bloodABSTRACT
OBJECTIVE: The IKK complex regulates NF-kappaB activation, an important pathway implicated in the rheumatoid arthritis (RA) disease process. This study was undertaken to assess the efficacy of N-(6-chloro-7-methoxy-9H-beta-carbolin-8-yl)-2-methylnicotinamide (ML120B), a potent and selective small molecule inhibitor of IKKbeta. METHODS: Polyarthritis was induced in rats by injection of Freund's complete adjuvant into the hind footpad. ML120B was administered orally twice daily, either prophylactically or therapeutically. Paw volumes and body weights were measured every 2-3 days throughout the study. We assessed bone erosions by several methods: histologic evaluation, quantitative micro-computed tomography (micro-CT) imaging analysis, and measurement of type I collagen fragments in the serum. Quantitative polymerase chain reaction was used to evaluate expression of messenger RNA for genes related to inflammation and to bone and cartilage integrity. RESULTS: Oral administration of ML120B inhibited paw swelling in a dose-dependent manner (median effective dosage 12 mg/kg twice daily) and offered significant protection against arthritis-induced weight loss as well as cartilage and bone erosion. We were able to directly demonstrate that NF-kappaB activity in arthritic joints was reduced after ML120B administration. Also, we observed that down-regulation of the NF-kappaB pathway via IKKbeta inhibition dampened the chronic inflammatory process associated with rat adjuvant-induced arthritis. CONCLUSION: The results of the present study suggest that IKKbeta inhibition is an effective therapeutic approach to treat both the inflammation and the bone/cartilage destruction observed in RA. Methods for the determination of serum markers for bone and cartilage destruction, as well as micro-CT analysis, may aid in predicting and evaluating the therapeutic efficacy of IKKbeta inhibition therapy in humans.
