[Reduction of unstable and dislocated hips applying the Tübingen hip flexion splint?]. / Die Tübinger Hüftbeugeschiene als Repositionsorthese?

BACKGROUND: The indication for the use of the Tübingen hip flexion splint is a dysplastic hip without instability. According to current knowledge dysplastic unstable or dislocated hips should be treated with a stable retention device such as a modified Fettweis cast. The aim of this study was to evaluate the treatment effect of the Tübingen hip flexion splint when applied to dysplastic unstable hips (type IIc unstable according to the classification of Graf) and dislocated hips (types D, III and IV according to the classification of Graf) within the first week of life. PATIENTS AND METHODS: All newborns with an unstable hip type IIc or worse detected by ultrasound in the first week of life were treated with a Tübingen hip flexion splint. A prospective cohort trial was performed between November 2007 and December 2010. The initial hip type according to the ultrasound classification of Graf, the start and the duration of treatment with the Tübingen hip flexion splint as well as the rate of success were evaluated. Due to the small number of patients non-parametric tests were used for statistical analysis. RESULTS: A total of 50 dysplastic unstable or dislocated hips in 42 newborns were treated with the Tübingen hip flexion splint. The distribution of pathological hip types was 6 type IIc unstable, 33 type D, 10 type III and 1 type IV. Therapy was started on average on day 3.5 (range 1-8 days) of life and 49 out of 50 hips were successfully treated with the Tübingen hip flexion splint. Solely the type IV hip could not be reduced in the Tübingen hip flexion splint. Thus 98% of the dysplastic unstable or dislocated hips were successfully converted into type I hips with an α-angle of more than 64° in the splint. The mean time for achieving an α-angle ≥ 64° was 51.6 ± 18.9 days (range 21-87 days). No statistically significant relationship was found between the duration of therapy and the time when treatment was started, early or late within the first week of life (p = 0.152). Furthermore, no correlation was detected between the duration of therapy and the initial hip type determined by ultrasound (p = 0.886). In all successfully treated cases therapy could be discontinued during the exponential part of Tschauner's maturation curve of hip development. CONCLUSION: When recognized within the first week of life dysplastic unstable hips (type IIc unstable according to the classification of Graf) and dislocated hips with a cranially dislocated cartilage roof (types D and III according to the classification of Graf) can be successfully treated with the Tübingen hip flexion splint provided that the parents show good compliance concerning the treatment regimen.

Qualitative highly divergent nuclear export signals can regulate export by the competition for transport cofactors in vivo.

Nucleo-cytoplasmic transport of proteins is mediated by nuclear export signals, identified in various proteins executing heterologous biological functions. However, the molecular mechanism underlying the orchestration of export is only poorly understood. Using microinjection of defined recombinant export substrates, we now demonstrate that leucine-rich nuclear export signals varied dramatically in determining the kinetics of export in vivo. Thus, nuclear export signals could be kinetically classified which correlated with their affinities for CRM1-containing export complexes in vitro. Strikingly, cotransfection experiments revealed that proteins containing a fast nuclear export signal inhibited export and the biological activity of proteins harboring a slower nuclear export signal in vivo. The affinity for export complexes seems therefore predominantly controlled by the nuclear export signal itself, even in the context of the complete protein in vivo. Overexpression of FG-rich repeats of nucleoporins affected a medium nuclear export signal containing protein to the same extent as a fast nuclear export signal containing protein, indicating that nucleoporins appear not to contribute significantly to nuclear export signal-specific export regulation. Our results imply a novel mode for controlling the biological activity of shuttle proteins already by the composition of the nuclear export signal itself.