Bone loss: prosthetic and augmentation method.
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Biomechanical Phenomena↗
Biomedical subjects
R D Scott
Publications and source records attributed to R D Scott.
Knee challenges: what would you do?
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Adult↗
Duplication of medial erosion in unicompartmental knee arthroplasties.
Osteoarthritis of the medial compartment of the knee often shows a specific pattern of anterior wear. Review of our revisions from a series of medial metal-backed Brigham unicondylar knee replacements performed between 1983 and 1989 showed that this wear pattern was common on the tibial polyethylene surface. We reviewed these cases retrospectively to compare the pattern of preoperative erosion with the wear of the prosthesis. In all 14 knees with severe anterior wear in a unicompartmental replacement, the prearthroplasty radiographs showed similar patterns, suggesting that the implanted tibial component may continue to be subjected to the same localised stresses that precipitated the failure of the original articular cartilage. Many tibial components implanted during the 1980s had an unacceptably thin anterior rim of polyethylene and it seems that greater thickness is essential at the anterior and peripheral margins of the tibial plateau.
Aged↗
NMR studies of 1H resonances in the 10-18-ppm range for cytosolic aspartate aminotransferase.
Continuing a previous investigation (Kintanar, A., Metzler, C. M., Metzler, D. E., and Scott, R. D. (1991) J. Biol. Chem. 266, 17222-17229), we have recorded 1H NMR spectra at 500 MHz in the 10-18-ppm range for the 93-kDa porcine cytosolic aspartate aminotransferase and for four specific mutant forms of the enzyme in which histidine 68 has been replaced by lysine or histidine 143, 189, or 193 has been replaced by glutamine. We have correlated resonances for apoenzyme, pyridoxamine and pyridoxal phosphate forms, and dicarboxylate complexes and have assigned imidazole NH resonances of active site histidines. The chemical shifts of several resonances undergo pH-dependent changes around the pKa of the Schiff base proton at the active site. Other resonances shift upon binding of dicarboxylates or other ligands. Phosphate or carboxylate ions, which can also occupy the site of the substrate's alpha-carboxylate, cause rapid exchange of the Schiff base proton. Although most resonances in the 10-18-ppm range disappear rapidly in D2O, a few are retained for months in the presence of the dicarboxylate inhibitor glutarate. We demonstrate that changes in chemical shifts and in exchange rates are sensitive indicators of electronic interactions of the enzyme with ligands and of conformational change. Nuclear Overhauser effects from NH protons have allowed us to identify resonances of CH protons of the imidazole rings of histidines 143, 189, and 193. Observed and predicted chemical shifts have been compared. We conclude that the net charge on this histidine cluster is zero but that some negative charge from the aspartate 222 carboxylate is donated inductively into the histidine 143 ring. Studies of the related enzyme from Escherichia coli are provided in an accompanying paper (Metzler, D. E., Metzler, C. M., Scott, R. D., Mollova, E. T., Kagamiyama, H., Yano, T., Kuramitsu, S., Hayashi, H., Hirotsu, K., and Miyahara, I. (1994) J. Biol. Chem. 269, 28027-28033). Our approach should be applicable to the study of active sites of a broad range of relatively large proteins.
Amino Acid Sequence↗
NMR studies of 1H resonances in the 10-18-ppm range for aspartate aminotransferase from Escherichia coli.
We have recorded 500-MHz 1H NMR spectra in the 10-18-ppm range for aspartate aminotransferase from Escherichia coli and for three specific mutant forms. Histidine 143 has been replaced by either alanine or asparagine. In the third mutant, tryptophan 140 has been replaced by phenylalanine. The NMR spectrum of the native enzyme is very similar to that of porcine cytosolic aspartate aminotransferase in the most downfield region. However, the resonances of the proton on the ring nitrogen of the pyridoxal 5'-phosphate (peak A) and on the His-143 imidazole ring (peak B) of the E. coli enzyme are broader and more readily lost at low pH or higher temperatures than those of the porcine enzyme. The possible role of tautomerism in promoting such broadening is discussed. In the histidine mutant proteins, peak A of the pyridoxal 5'-phosphate form is too broad to see under most conditions but is clearly present in the pyridoxamine phosphate form. Peak B is missing in the 2 histidine mutants. Observation of nuclear Overhauser effects further confirms the identity of B as the resonance of HN epsilon 2 of His-143 and that of peak D at approximately 11.8 ppm as HN epsilon 2 of His-189. The mutant spectra also provide insight into electronic interactions between groups in and near the active site which confirm and supplement conclusions drawn from spectra of porcine cAspAT. While no clear loss of a peak was observed for the Trp-140 mutant in its free form, the spectrum of the succinate complex lacked a strong band at 11.26 ppm. This may represent the Trp-140 indole NH proton which has been shifted downfield by binding to a succinate carboxylate group. While our results confirm the basic similarity of cytosolic aspartate aminotransferase and E. coli aspartate aminotransferase 1H NMR spectra, they also point out differences that may be useful in identifying resonances. A large number of mutant proteins have been prepared for the E. coli enzyme. The present results provide essential information for future study of these mutants and for study of NMR spectra of isotopically labeled enzyme.
Alanine↗
NMR spectroscopy of exchangeable protons of glucoamylase and of complexes with inhibitors in the 9-15-ppm range.
1H-NMR spectra have been recorded for glucoamylases I and II from Aspergillus awamori var. X100 and from A. niger in the 9-15-ppm region. At least 17 distinct peaks, many of them arising from single protons, are observed. These are designated A-Q, A being the furthest downfield. At least 9 of these are lost rapidly by exchange when the enzyme is placed in D2O. Peaks A, B, E and H undergo distinct shifts with pH change in the pH region 3-7. Several others undergo smaller shifts. Small differences are also seen between the enzymes from the two different sources. Binding of the pseudotetrasaccharide inhibitor acarbose leads to a 0.50-ppm downfield shift of peak B, other smaller changes, and retention of two additional protons in D2O. delta-D-gluconolactone induces shifts in peaks E, H, and L. The slow substrate maltitol causes peak A to broaden and shift, peaks J and K to shift and a new or greatly shifted resonance to appear at 15.4 ppm. It disappears as the maltitol is hydrolyzed. Treatment with iodoacetamide or diethyl pyrocarbonate leads to disappearance of peak D at 12.3 ppm. When this peak was irradiated strong nuclear Overhauser effects (NOE) were observed at 8.01 ppm and 7.22 ppm, positions expected for the C epsilon 1 and C delta 2 protons of an uncharged imidazole ring. We identify D as arising from the N epsilon 2 proton of His254 which is uncharged except at the lowest pH values. Other NOE and two-dimensional NOE spectra have provided additional information. Three mutant forms of the A. niger enzyme, in which tryptophan residues have been replaced by phenylalanine, have been examined. Because of shifts induced by changes in ring current and other environmental effects it is hard to make a direct identification of the resonances from the replaced indole NH protons. However, on the basis of a distinct NOE between peaks E and H we have identified these resonances as arising from the indole NH protons of Trp52 and Trp120. Other possible assignments are considered. The NMR spectra of the glucoamylases I, which have a starch binding domain of about 104 residues at the carboxyl terminus, show four sharp resonances in the 9.7-10.6-ppm range that are not present in the glucoamylases II, which lack this domain. These resonances no doubt represent the four indole NH ring protons from Trp543, Trp562, Trp590 and Trp615. Three of these are very sharp suggesting a high mobility of this domain.
Aspergillus↗
Bipolar revisions with bone-grafting for cavitary and segmental acetabular defects. A minimum 5-year follow-up study.
Bipolar revisions used in massive uncontained acetabular defects often lead to high migration rates and early clinical failure. Reconstructions for less severe acetabular bone deficiencies were studied radiographically and clinically. Thirty-two bipolar revisions with bone-grafting were performed for cavitary and segmental acetabular defects. The average follow-up period was 6 years (range, 5-8.4 years). Medial migration averaged 2.3 mm (range, 0-7 mm), oblique migration averaged 2.9 mm (range, 0-8 mm), and superior migration averaged 5.9 mm (range, 0-15 mm). Continued migration at the final follow-up evaluation was noted in all but nine hips. Arrested migration was observed when cavitary defects were encountered. Segmental medial wall defects resulted in increased medial migration. Segmental superior rim defects resulted in large amounts of superior migration. Preoperative Harris hip scores averaged 47 before surgery and 86 at the final follow-up evaluation. Postoperative clinical scores did not deteriorate with radiographic evidence of progressive migration. Six reoperations for femoral complications of fracture or loosening were performed at an average of 4.7 years with concomitant conversion of the bipolar prosthesis to a fixed cementless cup. One re-revision was performed for acetabular disassembly at 6.6 years. When cavitary defects exist, allografting with a bipolar endoprosthesis can provide durable reconstructions with excellent clinical function. Bipolar revisions are also a relatively simple means of providing stability in recurrent dislocation cases.
Adult↗
Cruciate-sparing total knee arthroplasty.
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Humans↗
Knee challenges: what would you do?
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Adult↗
Posterior cruciate supplementing total knee replacement using conforming inserts and cruciate recession. Effect on range of motion and radiolucent lines.
This study was performed to determine if a sagittally curved conforming tibial insert can be used with a retained, but balanced, posterior cruciate ligament without deleterious effects on range of motion (ROM) and tibial radiolucencies, as compared with a flatter insert that is less conforming and does not require cruciate balancing. The authors reviewed 50 consecutive primary knees implanted with flatter posterior lipped inserts and 50 consecutive primary knees with curved inserts and posterior cruciate ligament balancing. The average ROM for both groups was the same postoperatively as preoperatively: 111 degrees for the posterior lipped inserts and 113 degrees for the curved inserts. The incidence of tibial radiolucent lines was 8% for both groups. The authors conclude that sagittally curved, more conforming tibial inserts with retained, but balanced, posterior cruciate ligaments, do not adversely effect ROM and tibial radiolucencies. Their use forms an attractive compromise between the schools of cruciate preservation and cruciate substitution, maximizing their advantages while minimizing their disadvantages. Functional ROM can be achieved while bone stock is preserved, the joint line is restored, and wear characteristics are improved.
Female↗
Catastrophic failure of the polyethylene liner of uncemented acetabular components.
Ten cases are described of catastrophic failure of the polyethylene liner of three different designs of uncemented acetabular component. Failure occurred as a result of either 'wearthrough' to the metal backing, liner fracture or a combination of both, at a mean of 4.6 years after implantation (2 to 7.6). At revision there was metallosis in all hips and osteolysis of the femur or the pelvis in six. Catastrophic failure was seen only in cups with a minimum polyethylene thickness of less than 5 mm.
Acetabulum↗
Bipolar socket in protrusio acetabuli. 3-6-year study.
Twenty-two hips with protrusio acetabular deformity in 14 patients received bipolar socket hemiarthroplasty combined with bone-grafting to the medial wall defect. The surgical technique included crushed cancellous grafting and attention to adequate rim contact for the socket. Results were evaluated at a mean of 54 months after surgery (range, 36-76 months). On hip had thigh pain attributable to a loose femoral component. No patient had groin pain at follow-up examination. A satisfactory range of motion was achieved in all but one case, and an average increase of 40 points in the Harris hip score was realized. Radiographically, all acetabuli were returned to a more normal, inferolateral position. Socket migration (measured relative to the teardrop) in the range of 3-7 mm was noted in 5 hips; the remaining 17 hips displayed no or minimal migration of the socket (< 3 mm). The bipolar socket with crushed cancellous graft appears to be an acceptable surgical alternative in protrusio acetabuli, providing a reliable relief of pain, satisfactory functional results, and a restoration of acetabular bone stock in the majority of cases.
Acetabulum↗
Posterior polyethylene wear in posterior cruciate ligament-retaining total knee arthroplasty. A case study.
Controversy over whether to retain the posterior cruciate ligament (PCL) during primary total knee arthroplasty continues. Both the retaining and substituting designs have their respective advantages and disadvantages. In order to capitalize on the advantages of the PCL retaining design, precise techniques in ligament balancing are required. An incorrectly tensioned PCL--too tight or too loose--may exaggerate the disadvantages of the retaining design and lead to early catastrophic failure. Three cases of early catastrophic posterior wear are presented. Although no definite documentation of excessive PCL tension is available, the authors feel that this may have had a significant role in the etiology of this wear pattern. Possible causes of incorrect PCL tension as well as intraoperative techniques to balance the PCL properly are discussed.
Aged↗
Role of apical and basolateral secretion in turnover of glutathione in LLC-PK1 cells.
Previous clearance measurements have established that the rapid turnover of renal proximal tubular glutathione is in part due to apical secretion and degradation by gamma-glutamyltranspeptidase, an ectoenzyme that is primarily associated with the brush-border membrane. The relationship between glutathione turnover and secretion was further characterized using confluent cultures of LLC-PK1 cells grown on nitrocellulose supports. The resulting cell layer was impermeable to [3H]inulin and exhibited a polarized expression of gamma-glutamyltranspeptidase. Incubating cells with 5 mM buthionine sulfoximine, an inhibitor of glutathione synthesis, produced an 86% inhibition of [35S]cystine incorporation into intracellular glutathione. Under these conditions, the prominent intracellular pool of glutathione turns over with an apparent half-life of 4 h and a first-order rate constant of 0.17 h-1. This turnover is unaffected by pretreatment with AT-125, an inhibitor of gamma-glutamyltranspeptidase. The rate of accumulation of glutathione in the apical and basolateral medium of cells pretreated with AT-125 was 22 and 34 nmol.mg protein-1.h-1, respectively. The combined secretion was equivalent to the calculated turnover rate of intracellular glutathione (57 nmol.mg protein-1.h-1). Therefore, the combined processes of apical and basolateral secretion can account for the turnover of intracellular glutathione in LLC-PK1 cells.
Animals↗
The importance of the role of the patient in the outcome of schizophrenia.
The Family Interpersonal Perception Test (FIPT) was used to explore the relationships between schizophrenic patients and their parents, and how these related both to relapse in the year after discharge and to improvement in social functioning. Forty schizophrenic patients and their parents were tested during their first ever admission to hospital and again two years later. Parents' and patient's views of each other were more negative in those with worse outcome, but what most significantly distinguished groups with different outcomes was how patients expected their parents to see them. The FIPT, therefore, reveals patterns of interaction in which the patient's role in outcome is at least as important as that of the parents, and can aid the identification of specific features with which to work in therapy.
Adolescent↗
Capitellocondylar total elbow replacement in rheumatoid arthritis. Long-term results.
We evaluated the long-term results of 202 capitellocondylar total elbow replacements that had been performed, from July 1974 through June 1987, in 172 patients. The duration of follow-up averaged sixty-nine months (range, twenty-four to 178 months). At the most recent follow-up examination, use of a 100-point rating score demonstrated an improvement from an average preoperative score of 26 points (range, 2 to 50 points) to an average postoperative score of 91 points (range, 45 to 100 points). The most improvement occurred in the categories of relief of pain, functional status, and range of motion in all planes except extension. The improvements in these categories and in the roentgenographic appearance that were seen in the early postoperative period did not deteriorate with time. The average preoperative arc of motion at the elbow ranged from -37 degrees of extension to 118 degrees of flexion. The average postoperative arc of motion at the elbow ranged from -30 degrees of extension to 135 degrees of flexion. Supination improved from 45 degrees preoperatively to 64 degrees postoperatively; pronation improved from 56 degrees preoperatively to 72 degrees postoperatively. The roentgenograms showed a radiolucent line adjacent to eight humeral and nineteen ulnar components; most of the lines were incomplete and one millimeter wide or less. Revision of the prosthesis was necessary in three elbows (1.5 per cent) because of loosening without infection, and in three additional elbows because of dislocation of the prosthesis. Complications included deep infection in three elbows (1.5 per cent); problems related to the wound in fifteen (7 per cent); permanent, partial sensory ulnar-nerve palsy in five (2.5 per cent); permanent, partial motor ulnar-nerve palsy in one (0.5 per cent); and dislocation in seven (3.5 per cent).
Adult↗
Can islet cell antibodies predict IDDM in the general population?
OBJECTIVE: To evaluate the likely prognostic significance of ICAs in children with no family history of IDDM. RESEARCH DESIGN AND METHODS: We examined the prevalence of ICAs in 2925 English schoolchildren aged 9-13 yr and in 274 age-matched siblings of children with diabetes from the same region, and we compared the estimated risk of progression to diabetes within 10 yr in the two groups. RESULTS: ICAs were present at levels > or = 4 JDF U in 2.8% of schoolchildren and 6.6% of siblings and at > or = 20 JDF U in 0.8% of schoolchildren and 2.2% of siblings. Although ICAs are only 2-3 times more prevalent in siblings than schoolchildren, the estimated cumulative risk that siblings will progress to diabetes by age 21 is 13 times greater (2.8 vs. 0.21%). CONCLUSIONS: ICAs are unexpectedly prevalent in English schoolchildren, but only a small minority, with this evidence of immune activation directed against islet cells, will progress to diabetes. Although ICAs alone have limited predictive value in the general population, combining two or more predictive tests in series could achieve a level of prediction equivalent to that now obtained in first-degree relatives.
Adolescent↗