Diagnostic and treatment differences among experienced shoulder surgeons for instability conditions of the shoulder.

OBJECTIVE: To quantify interobserver agreement in the diagnosis and treatment of shoulder instabilities among expert North American shoulder surgeons. We hypothesized that interobserver consistency among this group will be significantly low in both diagnosis and treatment. DESIGN: Survey/Descriptive Epidemiology Study. SETTING: Self-administered survey via e-mail. PARTICIPANTS: Active members of American Shoulder and Elbow Surgeons (ASES) and JOINTS Canada (Joined Orthopaedic Initiatives for National Trials of the Shoulder), whose practices consisted primarily of shoulder surgery. INTERVENTIONS: Participants were sent a self-administered survey via e-mail and polled as to their choice of diagnosis and treatment in 5 different shoulder conditions. MAIN OUTCOME MEASUREMENTS: A Kappa coefficient of agreement, Ksc, was used to measure relative interobserver reliability. RESULTS: Overall response rate was 62.7% (42/67 surveys). The level of interobserver reliability was fair (Ksc 0.38, P < 0.0001) to almost perfect (Ksc 0.97, P < 0.0001) in diagnosing shoulder instability and slight (Ksc 0.23, P < 0.0001) to substantial (Ksc 0.69, P < 0.0001) for therapeutic approach. The greatest diagnostic differences were noted for a painful shoulder in a throwing athlete with subtle anterior instability (Ksc 0.43, P < 0.0001) and for a patient with voluntary posterior instability with an asymptomatic sulcus sign (Ksc 0.38, P < 0.0001). The greatest differences in treatment choice were for the throwing athlete with subtle anterior instability (Ksc 0.38, P < 0.0001), a patient with voluntary posterior instability (Ksc 0.34, P < 0.0001), and a patient with bidirectional instability (Ksc 0.23, P < 0.0001). CONCLUSIONS: These inconsistencies highlight the need for greater awareness and standardization of diagnostic criteria. This work may serve as the foundation for more universal treatment plans and subsequently more meaningful clinical outcomes.

Human airway smooth muscle cells express the high affinity receptor for IgE (Fc epsilon RI): a critical role of Fc epsilon RI in human airway smooth muscle cell function.

Several reports suggest that activated airway smooth muscle (ASM) cells are capable of generating various proinflammatory mediators, including cytokines and chemokines. However, little is known about the mechanism involved in this process. In this regard, we have examined the expression and the role of the high affinity IgE receptor (Fc epsilonRI) by ASM cells. Human ASM cells were found to constitutively express transcripts coding for alpha, beta, and gamma subunits of Fc epsilonRI. Flow cytometry and Western blot analysis confirmed the expression of Fc epsilonRI alpha-chain protein. Interestingly, Fc epsilonRI alpha-chain immunoreactivity was also demonstrated in smooth muscle within bronchial biopsies of asthmatic subjects. Cross-linking of Fc epsilonRI induced mobilization of free calcium in ASM cells, one of the critical signals to trigger smooth muscle contraction. Furthermore, cultured ASM cells released IL-4, IL-13, IL-5, and eotaxin but not IFN-gamma, when sensitized with IgE followed by anti-IgE Ab cross-linking. The addition of anti-Fc epsilonRI alpha-chain Abs directed against IgE binding site inhibited this release. Taken together, these results suggest a potential new and important mechanism by which ASM cells may participate in airway inflammation and bronchoconstriction associated with allergic asthma.

The RhoA/Rho kinase pathway regulates nuclear localization of serum response factor.

RhoA and its downstream target Rho kinase regulate serum response factor (SRF)-dependent skeletal and smooth muscle gene expression. We previously reported that long-term serum deprivation reduces transcription of smooth muscle contractile apparatus encoding genes, by redistributing SRF out of the nucleus. Because serum components stimulate RhoA activity, these observations suggest the hypothesis that the RhoA/Rho kinase pathway regulates SRF-dependent smooth muscle gene transcription in part by controlling SRF subcellular localization. Our present results support this hypothesis: cotransfection of cultured airway myocytes with a plasmid expressing constitutively active RhoAV14 selectively enhanced transcription from the SM22 and smooth muscle myosin heavy chain promoters and from a purely SRF-dependent promoter, but had no effect on transcription from the MSV-LTR promoter or from an AP2-dependent promoter. Conversely, inhibition of the RhoA/Rho kinase pathway by cotransfection with a plasmid expressing dominant negative RhoAN19, by cotransfection with a plasmid expressing Clostridial C3 toxin, or by incubation with the Rho kinase inhibitor, Y-27632, all selectively reduced SRF-dependent smooth muscle promoter activity. Furthermore, treatment with Y-27632 selectively reduced binding of SRF from nuclear extracts to its consensus DNA target, selectively reduced nuclear SRF protein content, and partially redistributed SRF from nucleus to cytoplasm, as revealed by quantitative immunocytochemistry. Treatment of cultured airway myocytes with latrunculin B, which reduces actin polymerization, also caused partial redistribution of SRF into the cytoplasm. Together, these results demonstrate for the first time that the RhoA/Rho kinase pathway controls smooth muscle gene transcription in differentiated smooth muscle cells, in part by regulating the subcellular localization of SRF. It is conceivable that the RhoA/Rho kinase pathway influences SRF localization through its effect on actin polymerization dynamics.