Spinal instrumentation. Biomaterial, biomechanical, and clinical aspects.
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Biocompatible Materials↗
Biomedical subjects
J N Weinstein
Publications and source records attributed to J N Weinstein.
Anatomic and technical considerations of pedicle screw fixation.
Pedicle screw systems provide significant and, in many cases, improved and previously unattainable spinal fixation. However, pedicle screw systems represent difficult surgical techniques involving several potential problems and complications. Only by detailed knowledge of the anatomy of the spine, with a clear understanding of the pedicle screw systems implementation, can the risks of complications be minimized.
Blood Vessels↗
Differential diagnosis and surgical treatment of pathologic spine fractures.
The prognosis for survival has improved dramatically for cancer patients over the past three decades. Advances in systemic therapy have prolonged survival even in those who cannot be cured. The importance of managing spinal column disease and protecting the spinal cord has subsequently been amplified. Almost any patient presenting with detectable neurologic function and enough physical reserve to withstand an operation will benefit from a spinal stabilization, pain relief, and neural decompression; there are few exceptions. Advances in surgical technique and biomaterials have not only improved survival and functional outcome, they have diminished many of the postoperative complications that plagued earlier treatment techniques. Methods of preventing or correcting iatrogenic deformity have improved outcome. Newer fixation techniques promise to eliminate many of the causes of hardware and fixation failure previously seen. Improved medical management, antibiotics, and preoperative planning, along with techniques of preoperative embolization and early postoperative mobilization have made surgical management much less risky. Vertebrectomy, considered a last alternative in the past, is now coming to be seen as the conservative approach to tumor management in many situations. Appropriate surgical treatment can have a dramatic impact on function and outcome in patients with tumors of the spinal column, and should never be dismissed as an option without serious consideration. Advances in fixation systems, local and systemic therapy, and in our understanding of the biology of cancer promise even greater improvements for the future.
Adult↗
New joint prediction algorithm (Q7-JASEP) improves the prediction of protein secondary structure.
The classical problem of secondary structure prediction is approached by a new joint algorithm (Q7-JASEP) that combines the best aspects of six different methods. The algorithm includes the statistical methods of Chou-Fasman, Nagano, and Burgess-Ponnuswamy-Scheraga, the homology method of Nishikawa, the information theory method of Garnier-Osgurthope-Robson, and the artificial neural network approach of Qian-Sejnowski. Steps in the algorithm are (i) optimizing each individual method with respect to its correlation coefficient (Q7) for assigning a structural type from the predictive score of the method, (ii) weighting each method, (iii) combining the scores from different methods, and (iv) comparing the scores for alpha-helix, beta-strand, and coil conformational states to assign the secondary structure at each residue position. The present application to 45 globular proteins demonstrates good predictive power in cross-validation testing (with average correlation coefficients per test protein of Q7, alpha = 0.41, Q7, beta = 0.47, Q7,c = 0.41 for alpha-helix, beta-strand, and coil conformations). By the criterion of correlation coefficient (Q7) for each type of secondary structure, Q7-JASEP performs better than any of the component methods. When all protein classes are included for training and testing (by cross-validation), the results here equal the best in the literature, by the Q7 criterion. More generally, the basic algorithm can be applied to any protein class and to any type of structure/sequence or function/sequence correlation for which multiple predictive methods exist.
Algorithms↗
Relative differences in the binding free energies of human immunodeficiency virus 1 protease inhibitors: a thermodynamic cycle-perturbation approach.
Peptidomimetic inhibitors of the human immunodeficiency virus 1 protease show considerable promise for treatment of AIDS. We have, therefore, been seeking computer-assisted drug design methods to aid in the systematic design of such inhibitors from a lead compound. Here we report thermodynamic cycle-perturbation calculations (using molecular dynamics simulations) to compute the relative difference in free energy of binding that results when one entire residue (valine) is deleted from one such inhibitor. In particular, we studied the "alchemic" mutation of the inhibitor Ac-Ser-Leu-Asn-(Phe-Hea-Pro)-Ile-Val-OMe (S1) to Ac-Ser-Leu-Asn-(Phe-Hea-Pro)-Ile-OMe (S2), where Hea is hydroxyethylamine, in two different (R and S) diastereomeric configurations of the hydroxyethylene group. The calculated (averaged for R and S) difference in binding free energy [3.3 +/- 1.1 kcal/mol (mean +/- SD); 1 cal = 4.184 J] is in good agreement with the experimental value of 3.8 +/- 1.3 kcal/mol, obtained from the measured Ki values for an equilibrium mixture of R and S configurations. Precise testing of our predictions will be possible when binding data become available for the two disastereomers separately. The observed binding preference for S1 is explained by the stronger ligand-protein interaction, which dominates an opposing contribution arising from the large desolvation penalty of S1 relative to S2. This calculation suggests that the thermodynamic cycle-perturbation approach can be useful even when a relatively large change in the ligand is simulated and supports the use of the thermodynamic cycle-perturbation algorithm for screening proposed derivatives of a lead inhibitor/drug prior to their synthesis.
Amino Acid Sequence↗
An analysis of monoclonal antibody distribution in microscopic tumor nodules: consequences of a "binding site barrier".
Rational in vivo application of monoclonal antibodies for diagnosis and therapy of cancer requires an understanding of both the global and microscopic pharmacology of macromolecular ligands. Here, we introduce a new mathematical model for antibody distribution into small, prevascular, densely packed nodules (representing either primary or metastatic tumor). For the analysis, we link together several aspects of antibody pharmacology: the global (whole body) pharmacokinetics; transcapillary transport into normal tissue interstitium surrounding the nodule; diffusion into the nodule; nonspecific binding and/or partitioning; specific binding to tumor antigen; metabolism; and lymphatic outflow from the tissue space. Input parameter values are estimated from experimental studies in vitro, in animals, and in clinical trials. Our aim is to explore the sensitivity of antibody localization to variation in three of the important parameters of this model: the rate of transcapillary transport; the rate of lymphatic outflow; and the antigen density. Predictions based on this analysis include the following: (a) High rates of transcapillary transport influx or low rates of lymphatic efflux will enhance antibody percolation into the tumor nodule at early times after injection and increase the average antibody concentration in the tumor at all times; (b) Changes in antibody influx rate will affect the antibody distribution in the tumor at earlier times than do changes in the efflux rate; (c) Reducing the antigen concentration will increase the uniformity of antibody penetration but lower the average concentration in the tumor at all times after injection; and (d) Counter to intuition, lowering the antigen concentration can increase the peak concentrations achieved toward the center of the nodule. If, in addition, there is any metabolism of bound antibody, the concentration-time integral (i.e., the "area under the curve") for the center of the nodule will also be increased by decreasing the antigen concentration. These predictions directly reflect the "binding site barrier" hypothesis of Weinstein et al. (Ann. NY Acad. Sci., 507: 199-210, 1987) and Fujimori et al. (Cancer Res., 49:5656-5663, 1989; J. Nucl. Med., 31:1191-1198, 1990). In general, and perhaps surprisingly until one considers the problem carefully, the parameters governing antibody percolation can have opposite effects on the uniformity of antibody distribution at early and late times. These calculations, using the PERC program set, were done for antibodies, but we believe that the "binding site barrier" will also prove important for other injected macromolecules, for at least some highly bindable injected small molecules, for lymphokines and cytokines released from transfected cells injected in vivo, and, indeed, for endogenous species such as the autocrine-paracrine factors.
Animals↗
Integrated microscopic-macroscopic pharmacology of monoclonal antibody radioconjugates: the radiation dose distribution.
Accurate dosimetry is essential for the assessment of radioimmunotherapy. Most often studied to date has been the macroscopic dosimetry related to organ and tumor distribution of the radiolabeled antibody, but the question of microscopic dose heterogeneity is also important. To address the latter issue, we have taken an integrated approach to the pharmacology, taking into account whole-body distribution, transcapillary transport, percolation through the tumor interstitial space, antigen-antibody interaction, and antibody metabolism. The first step is to simulate the spatial antibody concentration profile in a tumor as a function of time after i.v. (e.g., bolus) injection, using reasonable values for the parameters involved. The second step is to calculate, also as a function of time, the absorbed radiation dose distribution resulting from each concentration profile. Parameter values for IgG pharmacology and a radiation point source function for 131I are used to explore the effect of antibody distribution profiles on absorbed dose in the tumor. The geometry simulated corresponds to a spherical nodule of densely packed tumor cells. Absorbed doses are calculated for radiation from a single nodule (e.g., a micrometastasis or prevascular primary tumor) and for a cubic lattice of such nodules (e.g., corresponding to nodular lymphoma). As noted in our previous studies, there is a "binding site barrier." Binding to antigen retards antibody percolation into the nodules; high antibody affinity tends to decrease percolation and give a higher absorbed dose near the surface of each nodule. Heterogeneous antibody distribution results in a heterogeneous absorbed dose. This is more apparent in the case of radiation from a single nodule than it is for radiation from within an array of nodules. Dehalogenation results in a lower absorbed dose over time, and the effect is more apparent at later times after injection. PERC-RAD, the computer program package developed for these analyses, provides a convenient and flexible way to assess the impact of macroscopic and microscopic parameters on the distribution of radioimmunoconjugates and on the consequent profile of absorbed radiation dose in tumors. This mathematical model and the general principles developed here can be applied as well to other radiolabeled biological ligands.
Antibodies, Monoclonal↗
Direct intralymphatic injection of radiolabeled 111In-T101 in patients with cutaneous T-cell lymphoma.
Direct intralymphatic administration of radiolabeled monoclonal antibody in targeting antigen-bearing lymphoma cells in regional lymph nodes of patients with cutaneous T-cell lymphoma was evaluated. Seven consecutive patients undergoing staging lymphangiography received intralymphatic infusions of 111In-T101 to evaluate lymph node involvement. This procedure was accomplished without significant complication. The 111In-T101 rapidly distributed throughout the regional lymphatic compartment and passed into the systemic circulation. Tumor-bearing sites in the inguinal-femoral lymph nodes retained from 0.42 to 4.8% of the injected dose of radiolabeled antibody. Three patients were upstaged to Stage IVA based on tumor involvement found after radiolymphoscintigraphy-directed biopsy of groin lymph nodes, selected because of intense radioactivity by gamma camera imaging. Compared with previously reported s.c. antibody administration, there was a marked reduction in the radioactive exposure of normal tissues at the injection sites in the lower extremities. Direct intralymphatic delivery of 111In-T101 appears to be a feasible, efficient method for delivering therapeutic doses of radiolabeled antibody.
Adult↗
Application of extracorporeal shock wave lithotripter (ECSWL) in orthopedics. I. Foundations and overview.
In this paper we have reviewed the feasibility of using a shock wave lithotripter to loosen the interface between the bone and acrylic bone cement for revision arthroplasty. We have reviewed the physics of shock wave and its applications in medicine, especially its interaction with tissues. The calculations show that the energy is greatly reduced at the interface both in the soft tissue-bone interface and cement-bone interface. On the other hand, a tensile and compressive pressure can be operated at the cement-bone interface that can cause the interface to break if the pressure exceeds the tensile strength of the cement-bone interface. Subsequent papers will deal with in vitro and in vivo application of the shock wave in the treatment of the cement from the intramedullary canal.
Arthroplasty↗
Application of extracorporeal shock wave lithotripter (ECSWL) in orthopaedics. II. Dose-response and pressure distribution measurements.
In order to apply the extracorporeal shock wave lithotripter (ECSWL) technique to the loosening of the bone-cement interface for the extraction of the cement during revision arthroplasty it is essential to know the dose-response characteristics. The present study shows that the number of shocks needed to break the interface between a 2- and 6-mm-thick bovine femoral bone and bone cement is similar to the fatigue behavior of a material, that is, Log(N) = C(kV) + D, where N is the number of shock impulses, kV is the power setting of the lithotripter machine in kilovolts, and C and D are constants. Iso-pressure distribution of the traveling shock wave front through a simulated bone in a Plexiglass tube using Fuji pressure film showed quantitative pressure contours from which one can understand the effective area of shock wave and its distribution. The most effective area of the shock wave was about 1.5 cm in diameter at 23 and 25 kV with pressure at least 7.0 MPa which is more than sufficient to break the bone-cement interface in tension.
Animals↗
Application of extracorporeal shock wave lithotripter (ECSWL) in orthopaedics. III. In vitro and in vivo studies.
The present study was conducted to compare the push-out strength of the treated and control samples obtained after implantation of intramedullary rod in canine femurs with bone cement to simulate the femoral stem implantation for 2 weeks, 3 and 6 months. Contralateral femur served as control. The result showed a significant decrease in push-out interfacial strength after shock wave treatment (average 48.4% decrease compared with control, p less than 0.0001) which is similar to the in vitro results. There was no significant difference if the shock treatment was applied and left for 2 weeks or 4 weeks compared to the ones tested immediately after sacrifice. There were some soft tissue damage immediately following shock treatment in the focal area but this returned to normal in 2 weeks. Human cadaveric femoral bone experiment results showed that results are similar for both human cadaveric femoral bones and the canine bone (the dosage level was higher for the human bone than canine). The number of impacts used to extract the bone cement plug out of a human femur segment (5-cm long) decreased about 68% at 23 and 25 kV treatment power level. These preliminary studies indicate that the shock wave can be utilized to reduce the interfacial strength of the bone and bone cement although more studies are needed to assess its efficacy in terms of cost, long-term effect on patients and the exact mechanism of the loosening before this technique can be used clinically.
Animals↗
Ultrastructural changes in the dorsal root ganglion associated with whole body vibration.
Morphological changes were identified in dorsal root ganglion (DRG) neurons of rabbits exposed to whole body vibration. Light- and electron-microscopic analysis were carried out in six vibrated and four control animals. Analysis by light microscopy revealed DRG cells ranging from less than 20 mu to greater than 80 mu in diameter, with much less variation in nuclear diameter. Vibration had no effect on either cell or nuclear dimensions. There was no evidence of acute cellular injury in the vibrated specimens either on light or EM evaluation. However, mitochondria were increased 42% and lysosomes 33% in the vibrated specimens compared to controls. The incidence of nuclear membrane clefts was 2.70 per nucleus in control specimens and 3.74 per nucleus in vibrated specimens, an increase of 39%. These clefts were associated with numerous metabolic organelles, suggesting a relationship to cellular metabolism and, possibly, protein synthesis.
Animals↗
VSP stabilization of lumbar neoplasms: technical considerations and complications.
Variable screw placement (VSP) plates and pedicle screw fixation were used to stabilize eleven lumbar neoplasms. Blood loss and complications were comparable to other methods of posterior segmental fixation, although operative times were longer. Fewer levels were fused than for systems using sublaminar hooks or wires, with 8/11 patients treated with two level fixation. Four preoperatively irradiated patients experienced 43% of all complications and had 70% of the major complications. Wound infections occurred in 18%, vascular injuries in 18%, and transient neurologic deficits in 36% of our patients. Clinical pseudoarthroses developed in two patients, and tumor progression produced late instability in two patients with renal carcinoma. Thecal compression and late collapse led to therapeutic failure in four patients in 12-18 months. Fixation failure occurred in four patients, resulting from loosening of the plate on the screws in three patients, and breakage of a screw in one. Failure to adequately address anterior column disease was the primary cause of treatment failure in these patients. Proper seating of the plate on the pedicle screws is, likewise, crucial to construct stability and longevity. VSP instrumentation provides rigid fixation and allows more extensive tumor resection than traditional systems, while sparing vertebral motion segments. However, failure to address key technical and biomechanical principles may lead to serious complications.
Adult↗
In vitro comparative biomechanical analysis of transpedicular screw instrumentations in the lumbar region of the human spine.
An analysis of the load-displacement behavior of stabilized spines in comparison with intact spines was undertaken using fresh human cadaveric spines (T12/L1--sacrum). The three-dimensional load-displacement data of the five vertebral bodies of an intact specimen in clinically relevant loading cases were recorded using the Selspot II motion measuring system. After testing the intact specimen, an instability was created at the L4-5 level. The unstable motion segment was stabilized sequentially with three transpedicular screw instrumentations. The stabilized specimens were tested, and the data for the stabilized tests were normalized with respect to the intact data to determine the degree of stabilization achieved in various loading modes as a function of the three devices. The results showed that the three transpedicular devices included in this study were effective in imparting stability to the injured ligamentous spinal segment at a p less than 0.01 level of significance. The differences among the devices were not significant.
Aged↗
Effect of disc degeneration at one level on the adjacent level in axial mode.
Nonlinear three-dimensional finite element models of a ligamentous two motion segments spine specimen (L3-L4-L5) were developed to investigate the effects of disc degeneration, simulated at the L4-L5 level, on the biomechanical behavior of the adjacent intact L3-L4 motion segment. The disc degeneration was simulated by removing the hydrostatic capabilities of the nucleus and making the L4-L5 disc stiffer than a normal disc. The results of the degenerated model were compared with the predictions for a model in which the L4-L5 disc was left intact. The loads on the facets decreased, and intradiscal pressure in the intact L3-L4 disc increased as a result of disc degeneration compared with the intact model. The predicted increase in the intradiscal pressure and the associated increase in the disc bulge in the posterior region over time may trigger the degenerative process at the L3-L4 motion segment. This is in accordance with the Wolff's law; living tissue responds to chronic changes in stresses and strains. The limitations of the present two motion segments model and the potentials of multisegmental models are discussed.
Cadaver↗
Effects of rigidity of an internal fixation device. A comprehensive biomechanical investigation.
Internal fixation with instrumentation often accompanies surgical fusion to augment spinal stability, provide temporary fixation while the surgical fusion mass unites, and enhance postoperative mobilization of a patient. Some surgeons, however, feel that the existing plate-screw designs are too rigid and are the primary cause of "iatrogenic" adverse effects clinically observed. A three-part study, involving in vitro experimental protocol, analytical finite-element-based models, and an in vivo canine investigation, was undertaken to study the role of decreasing rigidity of a device on the biomechanical response of the stabilized segments. Two alternatives--the use of one variable screw placement (Steffee plate [unilateral, 1VSP model]) as opposed to two VSP plates (bilateral, 2VSP model) and two VSP plates with polymer washers placed in between the integral nut and plate (2MVSP model)--were considered for achieving a reduction in the rigidity of the conventional VSP system. The load-displacement data obtained from the in vitro experiments and the stress distributions within the stabilized and intact models predicted by the finite-element models revealed that the unilateral VSP system is less rigid and is likely to reduce stress shielding of the vertebral bodies compared with the 2VSP model. The undesirable effects associated with the use of the 1VSP plate system are the presence of coupled motions due to the inherent asymmetry and the likely inability to provide enough rigidity for decompression procedures requiring a complete excision of the disc. The use of two MVSP plates overcomes these deficiencies.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Intraspinal synovial cysts. Magnetic resonance evaluation.
Five intraspinal synovial cysts in four patients were evaluated with noncontrast magnetic resonance imaging and magnetic resonance imaging with the contrast agent gadolinium diethylenetriaminepentaacetic acid. Useful findings included demonstration of both solid and cystic components, early enhancement of the solid component and cyst periphery, delayed enhancement of the cyst, persistent enhancement of the solid component and cyst capsule, enhancement of the apophyseal joint, and recognition of a possible connection between the cyst and apophyseal joint. Although computed tomographic findings of synovial cysts are quite characteristic for the diagnosis in most cases, contrast magnetic resonance imaging may provide additional information for a more definitive diagnosis.
Adult↗