The influence of patient-related factors and the position of the acetabular component on the rate of dislocation after total hip replacement.

The senior one of us performed 438 primary and 181 revision total hip arthroplasties with use of so-called modern prostheses between July 1983 and January 1994. Fifty-three patients, who had had forty-seven primary procedures and twelve revisions, either died or were lost to follow-up less than two years after the operation and were excluded from the study. The results for the remaining 446 patients (391 primary procedures and 169 revisions) were analyzed to determine the influence of patient-related and operative factors and the position of the acetabular component on the rate of dislocation. Dislocation occurred after thirty-two (6 per cent) of the 560 total hip arthroplasties: seventeen (4 per cent) of the 391 primary procedures and fifteen (9 per cent) of the 169 revisions (p = 0.046). There was no relationship between the variables of age, gender, obesity, or preoperative diagnosis and dislocation after either primary or revision arthroplasty. Seven (23 per cent) of the thirty arthroplasties in the patients who had a history of excessive intake of alcoholic beverages (more than 2.1 liters [seventy-two ounces] of beer or more than 0.2 liter [six ounces] of other alcoholic beverages a day) were followed by a dislocation compared with twenty-five (5 per cent) of the 530 arthroplasties in the patients who did not have such a history. This difference was significant for the patients who had had a revision arthroplasty (p = 0.00005), but with the numbers available we could not detect a difference for those who had had a primary arthroplasty (p = 0.264). Radiographic analysis was performed for thirty-two hips that had dislocated and thirty-two that had not (seventeen primary procedures and fifteen revisions in each group), matched exactly according to the type of prosthesis and the operative approach (but not age). We detected no association between either the version or the abduction angle of the acetabular component (within the range of 39 to 56 degrees for the primary prostheses and 38 to 57 degrees for the revision prostheses) and the risk of dislocation. Thirty of the thirty-two hips in each group had an abduction angle of the acetabular component that was in the so-called safe range of 30 to 50 degrees.

Structure and energetics of a non-proline cis-peptidyl linkage in a proline-202-->alanine carbonic anhydrase II variant.

The crystal structure of a human carbonic anhydrase II (CAII) variant, cis-proline-202-->alanine (P202A), has been determined at 1.7-A resolution, indicating that the wild-type geometry, including the cis-peptidyl linkage, is retained upon substitution of proline by alanine. The CO2 hydrase activity and affinity for sulfonamide inhibitors of P202A CAII are virtually identical to those of wild type. However, the substitution of cis-alanine for cis-proline decreases the stability of the folded state by approximately 5 kcal mol-1 relative to both the unfolded state and an equilibrium intermediate in guanidine hydrochloride-induced denaturation. This destabilization can be attributed mainly to the less favorable cis/trans equilibrium of Xaa-alanine bonds compared to Xaa-proline bonds in the denatured state although other factors, including increased conformational entropy of the denatured state and decreased packing interactions in the native state, also contribute to the observed destabilization. The high catalytic activity of P202A CAII illustrates that unfavorable local conformations are nonetheless endured to satisfy the precise structural requirements of catalysis and ligand binding in the CAII active site.

Engineering a cysteine ligand into the zinc binding site of human carbonic anhydrase II.

Substitution of cysteine for threonine-199, the amino acid which hydrogen bonds with zinc-bound hydroxide in wild-type carbonic anhydrase II (CAII), leads to the formation of a new His3Cys zinc coordination polyhedron. The optical absorption spectrum of the Co(2+)-substituted threonine-199-->cysteine (T199C) variant and the three-dimensional structure [Ippolito, J. A., & Christianson, D. W. (1993) Biochemistry (following paper in this issue)] indicate that the new thiolate side chain coordinates to the metal ion, displacing the metal-bound solvent molecule. The engineered thiolate ligand increases zinc binding (4-fold) and decreases catalytic activity substantially (approximately 10(3)-fold) but not completely. However, this residual activity is due to an active species containing a zinc-bound solvent ligand with the cysteine-199 side chain occupying an alternate conformation. The equilibrium between these conformers reflects the energetic balance between the formation of the zinc-thiolate bond and structural rearrangements in the Ser-197-->Cys-206 loop necessary to achieve this metal coordination. This designed His3Cys metal polyhedron may mimic the zinc binding site in the matrix metalloproteinase prostromelysin.