RESUMEN
Operative fixation of midshaft clavicle fractures is controversial with few biomechanical data to assist surgical decision making. The purpose of this 2-phase biomechanical investigation is to report on the effects of plate location and selection on the stability of midshaft clavicle fractures. Thirty matched pairs of human adult formalin-fixed clavicles were used. In the first phase, in which a 3.5-mm reconstruction plate and simulated midshaft transverse clavicle osteotomies were used, we observed the effect of superior plate placement compared with anterior placement on fracture rigidity, construct stiffness, and strength. In the second phase, in which simulated midshaft oblique clavicle osteotomies were repaired on the superior aspect, we compared the fracture rigidity, construct stiffness, and strength of the 3.5-mm reconstruction, 3.5-mm limited contact dynamic compression (LCDC), and 2.7-mm dynamic compression (DC) plates. Intact clavicles were prepared, potted, and tested for axial and torsional stiffness in an Instron test frame equipped with gimbaled fixtures. Clavicles were band-sawed to simulate an osteotomy, repaired, re-mounted on the test frame with shear and opening extensometers placed across the osteotomy site, and then tested to observe axial and torsional fracture rigidity and stiffness. Constructs were then loaded to failure in compression. First-order regressions were used to estimate fracture rigidity (in kilonewtons per millimeter)and retained construct stiffness (in kilonewtons per millimeter), whereas the maximum applied compressive load at collapse or gross deformation determined the failure load. Values for the comparisongroups were tested for significance at the 95% confidence level. In the first phase we found that constructs plated at the superior aspect of the clavicle exhibited significantly greater fracture rigidity and mean retained stiffness than the anterior location (P <.05). In the second phase we found that the torsional fracture rigidity of LCDC-plated constructs significantly exceeded that of the reconstruction and DC plates (P <.05), whereas the axial fracture rigidity of the LCDC-plated constructs significantly exceeded that of the reconstruction plate (P <.05). In retained stiffness the performance of the LCDC-plated constructs significantly exceeded that of the DC plate in torsion (P <.05), whereas in load to failure the LCDC plate withstood significantly more compressive load than the reconstruction plate (P <.05). We concluded that clavicles plated at the superior aspect exhibit significantly greater biomechanical stability than those plated at the anterior aspect. Furthermore, we concluded that the LCDC plate offers significantly greater biomechanical stability than the reconstruction and DC plates.
Asunto(s)
Placas Óseas , Clavícula/lesiones , Osteotomía/métodos , Anciano , Fenómenos Biomecánicos , Diseño de Equipo , Humanos , Ensayo de Materiales , Persona de Mediana Edad , Resultado del Tratamiento , Heridas y Lesiones/fisiopatología , Heridas y Lesiones/cirugíaRESUMEN
T-cell responses to alloantigens can occur either by "direct" recognition of donor MHC molecules, or "indirect" recognition of MHC peptides in association with self-MHC. To evaluate human T cells mediating indirect allorecognition, a CD4+ TCL and clones specific for HLA-A1 or HLA-B8 (residues 60-84) were generated from normal PBLs (A2,29 B62,- DR1,4 DQ3). Most clones were A1 specific (16 out of 17 tested), HLA-DR4 restricted (8 out of 8), and lysed targets pulsed with A1 peptide (16 out of 16). An amino acid substitution at position 86 of the DR4 beta chain (G -> V) abrogated the capacity of CD4+ CTLs to lyse target cells. Chloroquine treatment of A1-pulsed targets reduced their susceptibility to lysis, indicating a requirement for peptide processing. The TCL and clones were stimulated to proliferate by cells bearing intact HLA-A1 when autologous APCs were present, indicating that the epitope contained within the A1 60-84 peptide being recognized is produced when APCs process native HLA-A1. Furthermore, the clones and TCL did not recognize HLA-A1 on target cells carrying this allele plus self-HLA-DR4. These studies suggest a much wider role for CD4+ T cells in allograft immunity.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Antígenos HLA/inmunología , Fragmentos de Péptidos/inmunología , Linfocitos T Citotóxicos/inmunología , Presentación de Antígeno , Línea Celular , Células Clonales/inmunología , Citotoxicidad Inmunológica , Rechazo de Injerto , Antígeno HLA-A1/inmunología , Antígeno HLA-B8/inmunología , Antígenos HLA-DR/inmunología , Antígeno HLA-DR4/inmunología , Cadenas HLA-DRB1 , Humanos , Activación de Linfocitos , Fragmentos de Péptidos/síntesis químicaRESUMEN
To elucidate mechanisms by which human CD4+ cells mediated cytolytic activity, we studied the expression of cytolytic proteins and the effects of inhibitors and mAbs on T-cell clones. Of seven cytolytic CD4+ clones, three were specific for the HLA-DR17, while four recognized DR18. Anti-HLA-DR mAb and anti-CD4 mAb blocked lysis. In addition, N alpha-p-tosyl-L-lysine chloromethylketone (TLCK), a serine esterase inhibitor, as well as cytochalasin B and monensin, antagonists of secretory pathways, inhibited CD4+ CTLs, whereas the absence of extracellular Ca+2 or the presence of Ca+2 channel blockers partially inhibited cytotoxicity. CD4+ CTLs induced apoptosis of target cell nuclei and membrane damage simultaneously. The CD4+ clones synthesized perforin and granzyme B and expressed the granule-associated protein TIA-1. Our studies indicate that two distinct mechanisms may contribute to cytolysis by CD4+ clones: (1) a Ca+2-dependent mechanism associated with the cytotoxic granules and (2) a Ca+2-insensitive mechanism.