Publications

Multistate modeling methods are well-suited for analysis of some chronic diseases that move through distinct stages. The memoryless or Markov assumptions typically made, however, may be suspect for some diseases, such as hepatitis C, where there is interest in whether prognosis depends on history. This paper describes methods for multistate modeling where transition risk can depend on any property of past progression history, including time spent in the current stage and the time taken to reach the current stage. Analysis of 901 measurements of fibrosis in 401 patients following liver transplantation found decreasing risk of progression as time in the current stage increased, even when controlled for several fixed covariates. Longer time to reach the current stage did not appear associated with lower progression risk. Analysis of simulation scenarios based on the transplant study showed that greater misclassification of fibrosis produced more technical difficulties in fitting the models and poorer estimation of covariate effects than did less misclassification or error-free fibrosis measurement. The higher risk of progression when less time has been spent in the current stage could be due to varying disease activity over time, with recent progression indicating an "active" period and consequent higher risk of further progression.

PURPOSE

The purpose of this study was to compare the biomechanical properties of transosseous versus suture anchor repair of the subscapularis tendon. We also performed real-time measurement of contact area and pressure of the repair site under rotational loads.

METHODS

Six paired human cadaveric shoulders were subjected to rotational loading after repair of the subscapularis tendon. Both shoulders were randomized to transosseous or suture anchor repairs. Real-time pressure sensors were placed between the subscapularis tendon and lesser tuberosity. The repair was subjected to cyclical rotational loading and load-to-failure testing.

RESULTS

No significant difference was detected in initial pressurized contact area between transosseous repairs (1.70 +/- 0.99 cm(2), 57.88 +/- 30.02% footprint) and suture anchor repairs (1.08 +/- 0.58 cm(2), 34.26% +/- 17.32% footprint). Under cyclical loading, the conditioning elongation of transosseous repairs (0.64 +/- 0.40 mm) was significantly lower (P < .05) than that of suture anchor repairs (2.38 +/- 1.58 mm). No significant difference was found in mean pressurized contact area between the transosseous repairs (2.72 +/- 1.25 cm(2), 94.2% +/- 37.4% footprint) and suture anchor repairs (2.01 +/- 0.89 cm(2), 65.9% +/- 27.9% footprint). For suture anchor repairs, repair-site contact area was significantly (P < .05) smaller than the area of corresponding native insertional footprints; for transosseous repairs, no significant difference was detected. There were no significant differences in peak pressures between the 2 repairs. In the load-to-failure tensile test, there was no significant difference between transosseous repairs (453.2 +/- 66.1 N) and suture anchor repairs (392.6 +/- 78.0 N).

CONCLUSIONS

Transosseous and suture anchor repairs of the subscapularis tendon have comparable biomechanical properties. Despite increased conditioning elongation in suture anchor repairs, we found no significant differences in mean contact area between the 2 repairs under cyclical loading. The suture anchor repairs do have a smaller contact area than the native insertional area. Real-time pressure and contact area measurements enabled mapping of the repair site throughout cyclical loading.

CLINICAL RELEVANCE

Rotational loading of the subscapularis tendon may provide a more accurate representation of subscapularis tendon injuries. Both techniques showed adequate repair strength; however, neither surgical technique exhibited normal insertional behavior in this time-zero biomechanical study.

Ferritin is a spherical molecule composed of 24 subunits of two types, ferritin H chain (FHC) and ferritin L chain (FLC). Ferritin stores iron within cells, but it also circulates and binds specifically and saturably to a variety of cell types. For most cell types, this binding can be mediated by ferritin composed only of FHC (HFt) but not by ferritin composed only of FLC (LFt), indicating that binding of ferritin to cells is mediated by FHC but not FLC. By using expression cloning, we identified human transferrin receptor-1 (TfR1) as an important receptor for HFt with little or no binding to LFt. In vitro, HFt can be precipitated by soluble TfR1, showing that this interaction is not dependent on other proteins. Binding of HFt to TfR1 is partially inhibited by diferric transferrin, but it is hindered little, if at all, by HFE. After binding of HFt to TfR1 on the cell surface, HFt enters both endosomes and lysosomes. TfR1 accounts for most, if not all, of the binding of HFt to mitogen-activated T and B cells, circulating reticulocytes, and all cell lines that we have studied. The demonstration that TfR1 can bind HFt as well as Tf raises the possibility that this dual receptor function may coordinate the processing and use of iron by these iron-binding molecules.