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Biomedical subjects

R D Scott

Publications and source records attributed to R D Scott.

At least 109 records · Page 6Linked to original sources

Revision of failed unicondylar unicompartmental knee arthroplasty.

In a retrospective review of the cases of twenty-nine patients who had a revision of a failed unicondylar unicompartmental knee replacement, the cause of failure of the original unicondylar arthroplasty was found to be loosening of one or both components in sixteen patients, progression of disease in the opposite compartment in nine, patellofemoral symptoms in two, ligamentous instability in one, and malposition of the tibial component in one. A technical error had been made in sixteen of the patients, and ten of the errors were associated with the ultimate failure of the original unicondylar procedure. Ninety-three per cent of the failed unicompartmental arthroplasties were revised using a posterior cruciate-sparing total knee replacement. Bone grafts, augmentation with screws and cement, a long-stem component, or a combination of these were used in half of the patients. The average follow-up after the revision arthroplasty was 4.6 years.

Aged↗

Function of pyridoxal 5'-phosphate in glycogen phosphorylase: 19F NMR and kinetic studies of phosphorylase reconstituted with 6-fluoropyridoxal and 6-fluoropyridoxal phosphate.

19F NMR spectroscopic properties of glycogen phosphorylase reconstituted with 6-fluoropyridoxal (6-FPAL) and 6-fluoropyridoxal phosphate (6-FPLP) were investigated. Analysis of the contribution of chemical shift anisotropy to the line width of the 6-FPLP-enzyme signal shows that the coenzyme molecule is tightly bound to the protein. The chemical shift of the fluorine nucleus in the free 6-FPLP protein is pH independent from pH 6 to pH 9.1. When the 6-FPLP-enzyme forms complexes with AMP, AMP plus glucose-1-P, and AMP plus inorganic phosphate, signals at -11.0, -13.1, and -10.4 ppm are observed, respectively. These different chemical shifts indicate that the protein in each complex has a distinct conformation. The exchange rate between the 6-FPLP-protein-AMP complex and the same complex with bound glucose-1-P is estimated to be 3300 +/- 700 s-1, and that between the 6-FPLP-protein-AMP complex and with bound inorganic phosphate is 500 +/- 100 s-1. The former exchange rate is 13 times faster than that of the same process for the 6-FPAL-enzyme. Analysis of the effects of temperature on the 19F line shape of the 6-FPLP enzyme in the presence of ligands shows that the exchange rates between different complexes drop significantly between 20 and 10 degrees C. Within this temperature range, Arrhenius plots of the enzymatic activities of the native and 6-FPLP-enzymes at varied temperatures also show a pronounced curvature.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗

Twelve years' experience with posterior cruciate-retaining total knee arthroplasty.

The posterior cruciate ligament can be retained with advantage during routine total knee arthroplasty. This ligament is virtually always intact and functioning, even in rheumatoid patients. It is an important biologic stabilizer of the knee, capable of absorbing anterior-posterior shearing forces that otherwise must be borne by a constrained prosthesis and hence by the bone-cement interface. Its presence allows maintenance of the normal kinematics of the knee. Roll-back of the femur on the tibia can occur, enhancing flexion and improving the quadriceps moment. Substitution of the posterior cruciate ligament with the addition of prosthetic constraint will increase bone-cement reaction forces. These prostheses also require significant intercondylar femoral bone stock resection. The average range of motion of the early cruciate sacrificing design used in Insall's series was 94 degrees, 10 degrees or more less than now routinely seen with cruciate preservation. The bone-cement interface of the early total condylar knee with limited range of motion absorbed less force than it potentially might encounter with greater range of motion and increased function. Predictably, at long-term follow-up examination the newer cruciate-substituting prostheses that allow more physiologic range of motion might show higher radiolucent line rates and higher loosening rates than their cruciate-preserving counterparts. Only this information can settle the argument over whether the posterior cruciate ligament should be preserved, and if the objective is a knee with maximum flexion and maximum functional capability.

Femur↗

Studies of 6-fluoropyridoxal and 6-fluoropyridoxamine 5'-phosphates in cytosolic aspartate aminotransferase.

The chemical and spectroscopic properties of 6-fluoropyridoxal 5'-phosphate, of its Schiff base with valine, and of 6-fluoropyridoxamine 5'-phosphate have been investigated. The modified coenzymes have also been combined with the apo form of cytosolic aspartate aminotransferase, and the properties of the resulting enzymes and of their complexes with substrates and inhibitors have been recorded. Although the presence of the 6-fluoro substituent reduces the basicity of the ring nitrogen over 10 000-fold, the modified coenzymes bind predominately in their dipolar ionic ring forms as do the natural coenzymes. Enzyme containing the modified coenzymes binds substrates and dicarboxylate inhibitors normally and has about 42% of the catalytic activity of the native enzyme. The fluorine nucleus provides a convenient NMR probe that is sensitive to changes in the state of protonation of both the ring nitrogen and the imine or the -OH group of free enzyme and of complexes with substrates or inhibitors. The NMR measurements show that the ring nitrogen of bound 6-fluoropyridoxamine phosphate is protonated at pH 7 or below but becomes deprotonated at high pH around a pKa of 8.2. The bound 6-fluoropyridoxal phosphate, which exists as a Schiff base with a dipolar ionic ring at high pH, becomes protonated with a pKa of approximately 7.1, corresponding to the pKa of approximately 6.4 in the native enzyme. Below this pKa a single 19F resonance is seen, but there are two light absorption bands corresponding to ketoenamine and enolimine tautomers of the Schiff base. The tautomeric ratio is altered markedly upon binding of dicarboxylate inhibitors. From the chemical shift values, we conclude that during the rapid tautomerization a proton is synchronously moved from the ring nitrogen (in the ketoenamine) onto the aspartate-222 carboxylate (in the enolimine). The possible implications for catalysis are discussed.

Animals↗

Resonance Raman spectra of the pyridoxal coenzyme in aspartate aminotransferase. Evidence for pyridine protonation and a novel photochemical H/D exchange at the imine carbon atom.

Resonance Raman (RR) spectra are reported for aspartate aminotransferase from pig heart cytosol, and for inhibitor complexes. They are interpreted with reference to the previously analyzed spectra of pyridoxal phosphate (PLP) Schiff base adducts. This comparison shows that, as expected, the pyridine N atom is protonated in the native enzyme at pH 5, and in the glutarate complexes at pH 8.5, and that it is also protonated in the alpha-methylaspartate complex; the stabilization of the pyridine proton at high pH must be due to the interaction with aspartate 222 seen in the x-ray crystal structure. RR spectra of the erythro-beta-hydroxy-DL-aspartate complex, representing the p-quinoid enzyme intermediate, as well as of AlIII complexes of PLP Schiff bases with phenylalanine and tyrosine ethyl ester have been obtained via the coherent anti-Stokes Raman scattering technique, and partially assigned. A novel H/D exchange at the coenzyme C4' atom has been observed for the native enzyme in D2O, and has been determined, by a combination of NMR and RR measurements, to be due to the Raman laser irradiation. This photoprocess, which is not observed for PLP Schiff bases in aqueous solution, is attributed to a photoexcited p-quinoid intermediate, similar to that implicated in the enzyme mechanism. It is suggested that this intermediate is stabilized by protein interactions which localize charge on the phenolate O atom, plausibly a hydrogen bond from the nearby tyrosine 225. H/D exchange would then follow via the aldimine-ketimine interconversion known to take place in the enzyme reaction.

Animals↗

Clinical value of a sensitive immunoradiometric assay for TSH.

We have investigated a sensitive immunoradiometric assay for serum thyroid-stimulating hormone (TSH) in 45 thyrotoxic patients not on treatment, 464 euthyroid patients and 111 hypothyroid patients on replacement therapy. Forty-three thyrotoxic and seven euthyroid patients were found to have an undetectable TSH (less than 0.2 mIU/L). Previous work has shown a very clear separation of thyrotoxic and euthyroid patients using sensitive TSH assays. However, our extended study here has revealed that a significant number of euthyroid patients with undetectable TSH (1.5% in our study) are likely to be found if TSH becomes the initial test for thyroid function. Thirty of the hypothyroid patients on thyroxine were found to have undetectable TSH, but only one showed clinical signs of thyrotoxicosis. Most of the patients, although having raised serum free T4, had serum free T3 levels within the euthyroid range or just slightly elevated.

Adolescent↗

The use of a modified V-Y quadricepsplasty during total knee replacement to gain exposure and improve flexion in the ankylosed knee.

A modified V-Y quadricepsplasty technique is described that facilitates exposure for prosthetic replacement in the knee with limited preoperative motion. The technique allows increased postoperative flexion without increasing the final postoperative extension lag. Seven patients have undergone knee arthroplasty using this method. The average increase in flexion was 49 degrees. The average ultimate extension lag was 8 degrees.

Ankylosis↗

Total knee arthroplasty in rheumatoid arthritis.

Total knee replacement in rheumatoid arthritis has evolved into a very reliable procedure for the relief of pain and restoration of function. Minimum of two year follow-ups using the most recent components and surgical techniques show that pain relief is good in 97 per cent of patients and range of motion averages 111 degrees. Although the rheumatoid patient presents many potential hazards and problems because of systemic disease most of these can be minimized or overcome by meticulous attention to pre-operative evaluation, planning, and operative technique.

Arthritis, Rheumatoid↗

McKeever metallic hemiarthroplasty of the knee in unicompartmental degenerative arthritis. Long-term clinical follow-up and current indications.

Forty patients with forty-four unicompartmental McKeever metallic uncemented hemiarthroplasties were followed for five to thirteen years (average, eight years). Thirty-nine knees had a medial and five, a lateral arthroplasty. The age at surgery ranged from thirty-two to eight-two years (average, sixty-seven years). At the final follow-up, 70 per cent of the knees were rated as good or excellent. Seventy-nine per cent of the knees in patients who were less than sixty-five years old at the time of surgery were in these categories. Six knees (14 per cent) had required revision to either a unicompartmental or a bicompartmental total knee replacement. The average preoperative and postoperative knee flexion did not change, but knees with initially poor motion improved. The average preoperative flexion contracture of 10 degrees improved postoperatively to 5 degrees. Complications were rare and no cases of infection, peroneal palsy, or clinically detectable phlebitis occurred. Obesity did not seem to adversely affect the outcome. This study indicated that the McKeever unicompartmental metallic hemiarthroplasty can provide an attractive alternative in the treatment of unicompartmental degenerative arthritis when proximal tibial osteotomy is contraindicated or has failed or when the patient is too young, heavy, or active to consider total knee replacement.

Adult↗

Femoral component loosening in total knee arthroplasty.

From experience with over 1600 condylar-type total knee arthroplasties performed between 1974 and 1981, the authors identified 15 knees in which the femoral component had loosened and shifted into flexion on the end of the femur. This mode of failure was related to inadequate support of the prosthetic posterior condyle, which resulted from inaccurate surgical cuts, poor cementing technique, or deficient bone stock either primary or secondary to persistent rheumatoid synovitis. Newer prosthetic designs that allow for greater range of motion and maximal function will further test the critical posterior condylar bone interface, as a result of which a higher incidence of femoral component loosening with flexion shift may be seen. Femoral component design changes and surgical techniques that sustain the posterior femoral condyle metal-bone interface may thus be necessary. Femoral components with intramedullary stems may be appropriate for high-risk patients.

Adult↗

Bone scanning in the assessment of patellar viability following knee replacement.

In an attempt to diagnose avascular necrosis (AVN) of the patella, a potential complication of the surgical procedure, 99mTc-MDP bone scanning was performed pre- and postoperation in 37 patients treated by 41 total knee arthroplasties. The normal immediate postoperative scan should demonstrate increased radionuclide uptake in the patella when compared to preoperative scans. Decreased uptake was seen in four cases in the early postoperative period. This latter group was believed to be at risk for osteonecrosis and stress fracture of the patella. For this reason, prophylactic restriction of activity was instituted, with subsequent return of normal radionuclide uptake in the patella. Bone scanning provides an effective method of early diagnosis of patients at risk for the development of AVN and secondary patellar fractures following total knee arthroplasty.

Adult↗

Obturator-nerve palsy resulting from intrapelvic extrusion of cement during total hip replacement. Report of four cases.

Obturator neuropathy is an infrequently identified complication of total hip replacement that may cause debilitating pain. There have been isolated reports of this complication in the literature, but only one case has been published in which intrapelvic cement was the causative agent. We are describing the cases of four patients with obturator neuropathy after total hip replacement, documented by electromyography and attributed to intrapelvic extension of cement. In each patient the source of the symptoms was not initially apparent. In three of the patients the extruded cement and obturator nerve were explored surgically. One of the three patients was improved by obturator neurectomy. Of the other two patients, both treated by excision of cement, only one was improved. The fourth patient was not treated. Persistent pain in the groin and thigh, intrapelvic cement visible on plain roentgenograms, and adductor weakness after total hip replacement suggest that this complication has occurred. Electromyography can confirm the presence of obturator neuropathy. Based on this limited series, excision of the extruded cement and preservation of the nerve should be attempted only when the nerve is grossly normal and functional as determined by electrical stimulation at the time of surgical exploration; otherwise, obturator neurectomy should be considered.

Bone Cements↗

Tibial component fixation in deficient tibial bone stock.

A stylized wedge-shaped defect was created in the medial plateau of autopsy specimens of the tibia to evaluate methods for fixation in total knee arthroplasty. A series of tibial components was inserted by five different methods. With each method loading of up to 1780 N axially and a varus load of 1340 N at 28 Newton-meters were assessed. The vertical deflections of the medial and lateral sides of the tray relative to the bone were measured while bending of the stem was recorded with strain gauges. The greatest deflections occurred when cement alone filled the defect; only slight improvement resulted from the addition of two cancellous screws to buttress the metal tray. Further improvement occurred when solid spacers of Plexiglas or metal were used. Finally, the most secure support was obtained with an integral custom-made tibial component. A central stem 70 mm long carried 23%-38% of the axial load, considered useful in the situation of deficient proximal bone. A metal wedge was considered an acceptable alternative to a custom-made component and may prove useful in the reconstruction of tibial bone stock defects.

Biomechanical Phenomena↗

Total knee arthroplasty in juvenile rheumatoid arthritis.

From 1971 to 1981, total knee arthroplasty was performed on forty-eight knees in twenty-eight patients with juvenile rheumatoid arthritis at the Robert Breck Brigham (now Brigham and Women's) Hospital. Seventeen of these patients, with twenty-nine knee-replacement arthroplasties, were followed for from two to eleven years (average, five years) and are the basis for this study. The patients' ages at operation ranged from thirteen to thirty-nine years (average, twenty-three years). Six patients had undergone total hip arthroplasty prior to admission for total knee replacement, and five patients had a total hip replacement performed while they were hospitalized for the knee arthroplasty. Thirteen patients (twenty-one knees) had significant preoperative pain but only three (five knees) had severe discomfort. Four patients were unable to walk, three were household walkers, and ten were limited community walkers. Preoperative deformities of the knees ranged from 20 degrees of varus angulation to 35 degrees of valgus angulation. The average preoperative flexion deformity was 23 degrees and the arc of motion averaged 45 degrees. At follow-up, twenty of the twenty-one knees that had been significantly painful preoperatively were completely relieved of discomfort. The average arc of motion increased by 34 degrees, while in all but one knee the angular deformity had been corrected to zero to 10 degrees of valgus angulation. All but one patient became a limited or full community walker. Complications included one late deep infection and one posterior tibial subluxation. Four knees required subsequent resurfacing of the patella for treatment of pain. We now routinely resurface the patella in all patients with juvenile rheumatoid arthritis who have a total knee replacement. To date no prosthesis has required revision for loosening. Radiolucency of one millimeter or less about the prosthesis was noted at follow-up in eight (30 per cent) of the knees. As custom-made components were required in twelve of the twenty-nine knees, it is obvious that preoperative planning is crucial in the treatment of these patients. Our recent experience has shown that the use of preoperative and postoperative serial casts aids greatly in the correction of severe flexion deformity of the knee. Postoperative manipulation was required for twenty-one of the twenty-nine knees. Skeletal immaturity was not an absolute contraindication to surgery. We think that our results, which showed a marked improvement in both knee function and in quality of life, make the short and long-term risks of knee-implant surgery well worth taking in this patient population.

Adolescent↗

Pyrrolopyridine derivatives from pyridoxal 5'-sulfate.

A fluorescent derivative of lysine-258 isolated from the active site of aspartate aminotransferase modified by treatment of the apoenzyme with pyridoxal 5'-sulfate has been characterized as a substituted 2H-pyrrolo[3,4-c]pyridine. Similar pyrrolopyridines are produced in up to 20% yield by reaction of pyridoxal sulfate with simple alkylamines or with amino acids including lysine. The latter forms two products, one of which is identical with that isolated from the enzyme. The pyrrolopyridine derived from ethylamine has been characterized by proton and 13C NMR, ultraviolet-visible, and mass spectroscopy and by its chemical reactions.

Aspartate Aminotransferases↗

Covalently modified peptides isolated from aspartate aminotransferase after reaction with pyridoxal 5'-sulfate.

The apoenzyme form of cytosolic aspartate aminotransferase of pig hearts was allowed to react at room temperature with 1 equiv of pyridoxal 5'-sulfate. The resulting covalently modified enzyme was degraded with pepsin. Fluorescent tri-, tetra-, and hexapeptides were isolated and characterized as fragments of the active site sequence: Phe-Ser-Lys-Asn-Phe-Gly-Leu. This sequence contains a modified form (Lys) of lysine-258 that is known to form a Schiff base with pyridoxal phosphate in the active site. The peptides were further degraded by acid hydrolysis to give a fluorescent derivative of lysine with light absorption and chemical properties similar to those of the original modified enzyme. A related series of peptides were obtained from apoenzyme after reaction with the 5-carboxyethenyl analogue of pyridoxal 5'-phosphate.

Amino Acids↗