Effect of innominate and femoral varus derotation osteotomy on acetabular development in developmental dysplasia of the hip.

BACKGROUND: Open reduction for the treatment of hip dislocation due to developmental dysplasia of the hip in children of walking age is frequently combined with either a femoral varus derotation osteotomy or an innominate osteotomy; however, it remains unclear which of these procedures is preferable in terms of subsequent hip development. The purpose of the present study was to compare acetabular development in patients managed for dislocation of the hip with open reduction combined with one of the two osteotomies. METHODS: Patients between fifteen months and four years of age with hip dislocations that were treated at two different centers were compared. At one center, open reduction combined with a femoral varus derotation osteotomy was performed (thirty-eight patients), and at the other, open reduction combined with an innominate osteotomy was performed (thirty-three patients). In each group, one surgeon performed all of the operations. A total of 490 postoperative radiographs that were made over a mean follow-up period of 6.2 years were analyzed. We compared the change in acetabular index as well as several other radiographic criteria of acetabular development and hip stability over time. RESULTS: After osteotomy, the acetabular index improved in both groups; however, the acetabular index in patients who underwent a varus derotation osteotomy never improved as much as that in patients who underwent an innominate osteotomy, with a mean difference of 9.5 after four years (p < 0.0001). Similarly, the innominate osteotomy group demonstrated better acetabular architecture and hip stability over time as quantified by the change in the acetabular floor thickness (p = 0.03), lateral centering ratio (p < 0.0001), and superior centering ratio (p < 0.0001). CONCLUSIONS: In the present series, acetabular remodeling after open hip reduction and innominate osteotomy was more effective for reversing acetabular dysplasia and maintaining hip stability than open reduction combined with a femoral varus derotation osteotomy was. Long-term follow-up is necessary to determine whether the more favorable hip development following innominate osteotomy is associated with a lower incidence of premature degenerative hip disease.

Signals mediated by transforming growth factor-beta initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease.

It is unclear whether TGF-beta, a critical differentiation factor for T cells producing interleukin 17 (T(H)-17 cells), is required for the initiation of experimental autoimmune encephalomyelitis (EAE) in vivo. Here we show that mice whose T cells cannot respond to TGF-beta signaling lack T(H)-17 cells and do not develop EAE despite the presence of T helper cell type 1 infiltrates in the spinal cord. Local but not systemic antibody blockade of TGF-beta prevented T(H)-17 cell differentiation and the onset of EAE. The pathogen stimulus zymosan, like mycobacterium, induced T(H)-17 cells and initiated EAE, but the disease was transient and correlated with reduced production of interleukin 23. These data show that TGF-beta is essential for the initiation of EAE and suggest that disease progression may require ongoing chronic inflammation and production of interleukin 23.

Modulation of dendritic cell function by naive and regulatory CD4+ T cells.

The consequences of interactions between dendric cells (DCs) and either naive CD4+ T cells or regulatory CD4+CD25+ T cells on the expression of proinflammatory IL-6 and anti-inflammatory IL-10 in DC were examined over a period of 12 h, spanning the time frame during which stable T cell-DC interactions shape the development of tolerance and immunity in vivo. We demonstrate that the basal production of IL-6 and IL-10, which is initiated following DC stimulation with LPS, is modified in distinctly different ways by interaction with the two T cell populations. Naive CD4 T cells skew DC cytokine production toward IL-6 and suppress IL-10, whereas CD4+CD25+ T cells have the opposite effect. CD8 T cells or memory CD4 T cells do not influence basal cytokine production by stimulated DC. The effect of CD4+CD25+ T cells is dominant in coculture with naive CD4 T cells as long as inflammatory LPS is absent; the addition of LPS abrogates the suppression of IL-6. However, the modulating influence of CD4+CD25+ T cells remains evident in the enhancement of IL-10 production. Thus, mutual interactions between DC and CD4+ T cell subpopulations following contact with pathogens are likely to influence the strength and quality of incipient immune responses in the local microenvironment.

TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells.

We describe de novo generation of IL-17-producing T cells from naive CD4 T cells, induced in cocultures of naive CD4 T cells and naturally occurring CD4+ CD25+ T cells (Treg) in the presence of TLR3, TLR4, or TLR9 stimuli. Treg can be substituted by TGFbeta1, which, together with the proinflammatory cytokine IL-6, supports the differentiation of IL-17-producing T cells, a process that is amplified by IL-1beta and TNFalpha. We could not detect a role for IL-23 in the differentiation of IL-17-producing T cells but confirmed its importance for their survival and expansion. Transcription factors GATA-3 and T-bet, as well as its target Hlx, are absent in IL-17-producing T cells, and they do not express the negative regulator for TGFbeta signaling, Smad7. Our data indicate that, in the presence of IL-6, TGFbeta1 subverts Th1 and Th2 differentiation for the generation of IL-17-producing T cells.

Primary synovial chondromatosis of the subtalar joint affecting two brothers.

Primary synovial chondromatosis is a rare benign condition characterized by the formation of multiple cartilaginous nodules in the synovium of joints and on occasions tendon sheaths or bursae. A case of primary synovial chondromatosis affecting the subtalar joint is reported. The patient's brother developed the same condition affecting the same joint 2 years later. The proposed etiologies are discussed including the presence of the proto-oncogene C-erb B-2.