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Biomedical subjects

Thomas D Brown

Publications and source records attributed to Thomas D Brown.

18 recordsLinked to original sources
PubMed2003

Phase II trial of systemic continuous fluorouracil and subcutaneous recombinant interferon Alfa-2b for treatment of hepatocellular carcinoma.

PURPOSE: Because cirrhosis is extremely common in hepatocellular carcinoma (HCC) in the United States, and it precludes the use of several chemotherapy agents, this phase II trial of fluorouracil (FU) and recombinant interferon alfa-2b (rIFNalpha2b) in HCC was launched with the assumption that it could be tolerated by cirrhotics. PATIENTS AND METHODS: Forty-three patients with HCC (34), and fibrolamellar HCC (FLHCC; nine) were treated with continuous intravenous (IV) FU (200 mg/m2/d x 21 every 28 days) and subcutaneous (SC) rIFNalpha2b (4 million U/m2) three times weekly. Survival was determined in all 43 patients, and response could be assessed in 28 HCC and 8 FLHCC patients. RESULTS: The median ages of the patients were 63.5 and 19 years among HCC and FLHCC patients, respectively. Liver cirrhosis was present among 71% of HCC patients but among none of the FLHCC patients. Nine of 36 (25%; four of 28 [14%] HCC patients; five of eight [62.5%] FLHCC patients) patients in which a response could be assessed had a complete response (CR; one patient with FLHCC and no patients with HCC) or partial response (PR; eight patients [four HCC and four FLHCC patients]). Four HCC patients underwent resection, and two had a histologic CR; one HCC patient with a PR underwent orthotopic liver transplantation. One FLHCC patient also underwent resection without clear margins. Overall median survival was 19.5 months (95% confidence interval [CI], 11.2 to 27.8 months); median survival was 15.5 months (95% CI, 8.5 to 22.5 months) among HCC patients, and that of FLHCC patients was 23.1 months (95% CI, 10.3 to 35.9 months). Overall grade 3 or 4 toxicity included stomatitis (32.6%), fatigue (4.7%), and hematologic toxicity (9.3%). CONCLUSION: Continuous IV FU and thrice-weekly SC rIFNalpha2b are an effective treatment, especially for FLHCC, and may have a neoadjuvant role in this disease. This regimen has activity in HCC and can be tolerated even by cirrhotic patients.

Adolescent↗
PubMed2003

Kinematics, kinetics, and finite element analysis of commonplace maneuvers at risk for total hip dislocation.

Dislocation remains a disturbingly frequent complication of total hip arthroplasty (THA). Over the past several years, increasingly rigorous biomechanical approaches have been developed for studying dislocation, both experimentally and computationally. Realism of the input motion challenge data has lagged behind most other aspects of this body of work, and anterior dislocation maneuvers remain unstudied. To enhance realism of biomechanical studies of dislocation, motion data are here reported for ten THA-aged subjects, each repeatedly performing seven maneuvers known to be dislocation-prone. An optoelectronic motion tracking system and a recessed force plate captured the kinematics and ground reaction forces of these maneuvers. Using an established inverse dynamics model to estimate hip joint loading, 354 motion trials were evaluated using an existing finite element model of THA dislocation. Worst-case-scenario THA constructs were simulated (22 mm femoral head, acetabular cup orientations at the limit of the accepted safe zone), in order to deliberately induce impingement and dislocation. The results showed a high incidence of computationally predicted dislocation for all movements studied, but also that risk was very maneuver-dependent, with patients being six times more likely to dislocate from a low-sit-to-stand maneuver than from stooping. These new motion data hopefully will help facilitate systematic efforts to reduce the incidence of dislocation.

Activities of Daily Living↗
PubMed2003

Focal cryogen insults for inducing segmental osteonecrosis: computational and experimental assessments of thermal fields.

Orthopaedic management of femoral head osteonecrosis is a common clinical problem for which there presently is no good solution. Current animal models are inappropriate to study potential new solutions, since it has been difficult to replicate the natural history of structural collapse seen in the human disorder. Recently, progression to collapse was obtained for cryogenically induced osteonecrosis in emus, although the lesions involved were imprecisely controlled in terms of size or location. A new cryo-insult probe is here reported for the purpose of delivering well-prescribed local thermal insults in this new animal model, while minimizing damage to non-targeted regions. Finite element analysis was used to elucidate the influence of operator-controlled parameters upon the temporal/spatial variation of the thermal field. The numerical formulation includes convective heat transfer attributable to tissue bed perfusion. The computational results agreed closely with the results of thermocouple recordings in a companion bench-top experiment. The cryo-insult probe successfully produced segmental lesions in the emu model of sizes comparable to the computed freeze front diameters.

Animals↗
PubMed2003

Orthopaedic crossfire--Larger femoral heads: a triumph of hope over reason! In the affirmative.

The authors' wear studies of total hip arthroplasty cohorts have shown that less polyethylene wear and less deleterious effects of third body debris were found when smaller femoral head sizes were used. The authors' sliding-distance-coupled finite element model findings were corroborated by these clinical wear studies. Thus, with polyethylene on metal bearing surfaces, less wear should occur when smaller head sizes are used. Careful, precise component positioning is important to prevent dislocation.

Finite Element Analysis↗
PubMed2003

Gait cycle finite element comparison of rotating-platform total knee designs.

Functional load transmission and kinematic performance were compared for standard versus posterior-stabilized versions of a rotating-platform total knee implant, over a standardized loading cycle, using three-dimensional contact finite element analysis. These two design variants differ primarily in terms of the latter's polyethylene insert having a cam that engages with the femoral component during appreciable flexion, thereby inducing femoral component rollback. The finite element model, previously validated experimentally, afforded direct comparisons of anterior lift-off of the insert from the tibial tray, of bearing mobility (insert rotation about the pivot post), of femoral rollback, and of metal-on-polyethylene contact stresses at the bearing and backside surfaces of the insert. Both design variants generally performed comparably, exhibiting an internal and external rotation range of approximately 5 degrees, approximately 1.5 mm peak lift-off at the anterior aspect of the insert, and approximately 15 mm of posterior rollback, the respective maxima for both designs occurring at approximately the same instants in the gait cycle. However, the posterior-stabilized design had slightly more rollback, and slightly less anterior lift-off and rotation, than did the standard rotating-platform design. Peak polyethylene stresses occurred on the backside of the insert near the posterior edge of the medial compartment, the magnitude being approximately 18% higher for the posterior-stabilized design (21 MPa) than for the standard design.

Finite Element Analysis↗
PubMed2003

A biomechanical analysis of polyethylene liner cementation into a fixed metal acetabular shell.

BACKGROUND: A common clinical scenario encountered by an orthopaedic surgeon is a patient with a secure cementless acetabular shell and a failed polyethylene liner. One treatment option is to cement a new liner into the fixed shell. The purpose of this study was to evaluate technical variables to improve the mechanical strength of such cemented liner constructs. METHODS: The contributions of shell texturing, liner texturing, and cement mantle thickness (between the liner and the shell) were evaluated by comparing torsional strength (among nine groups of constructs) and lever-out strength (among eight groups of constructs). RESULTS: Failure almost always occurred at the cement-liner interface. The two exceptions (failure at the shell-cement interface) occurred with a polished, untextured shell with no screw-holes. This finding indicates that if a shell has existing texturing (such as holes), further intraoperative scoring of the shell is unnecessary, but some sort of texturing is necessary to avoid construct failure at the shell-cement interface. Textured liners had significantly (a = 0.05) greater torsional and lever-out strength than untextured liners. The greatest construct strength occurred when liner grooves were oriented so as to oppose the applied loading. A 4-mm-thick cement mantle resulted in slightly greater torsional strength than a 2-mm-thick cement mantle, and a 2-mm-thick cement mantle resulted in considerably greater lever-out strength than a 4-mm-thick cement mantle, but these differences were not significant. CONCLUSIONS: When cementing a liner into a well-fixed shell, a surgeon should ensure that both the shell and the liner are textured, as interdigitation of the cement with the shell and the liner is crucial to the mechanical strength of this construct.

Arthroplasty, Replacement, Hip↗
PubMed2002

Interfragmentary surface area as an index of comminution energy: proof of concept in a bone fracture surrogate.

Fracture mechanics theory postulates a monotonic relationship between energy absorption and fracture surface generation. We hypothesized that this relationship was demonstrable to the point that, on a continuous scale, comminuted fractures created with disparate levels of energy delivery could be discriminated. Using a bone fracture surrogate in conjunction with digital image analysis of CT fracture data, we measured the surface area freed by controlled, discrete fracture simulations. Prior to these simulations, the reproducibility of the digital image analysis algorithm was validated with repeated measurements by two different operators. The parametric fracture series results showed a statistically significant difference in measured de novo surface area between four specimen groups, over a range of input energies from 1.4 x 10(10)-9.1 x 10(10)J/m(3) (or 12.5-80.2J/specimen). The results of this study provide confirmation that comminution severity can indeed be measured on a continuous scale, based on energy absorption (another clinically meaningful index).

Algorithms↗
PubMed2002

Spatial distribution of hip capsule structural and material properties.

Contemporary computational models potentially allow the practical incorporation of the effects of a joint capsule on both motion and the loads transmitted to the other parts of the joint. However, the required material properties have not been available for this purpose. To determine these properties we took both hip joints from five fresh-frozen, nondiseased cadavers. Following dissection and potting of the hemi-pelvis, distraction of the intact joint was conducted to measure the structural tangent stiffness of the joint capsule. Anatomical insertion points of the hip capsule were then recorded, and a complete capsulectomy was performed. Once excised, the capsule was sectioned into eight, approximately even sectors, and initial geometrical measurements were recorded for material property calculations. Material properties (i.e., structural tangent stiffness, failure load, ultimate strength, tangent modulus) were calculated using the load-displacement and geometric data collected for each of the sectors. This specimen-to-specimen thickness variability reveals significantly lower (p<0.01) average tangent structural stiffness values in the posterior-inferior portion of the capsule. Explorations of hip stability using numerical models can now be enhanced by incorporation of these experimental capsule data.

Aged↗
PubMed2002

Effects of acetabular component orientation on dislocation propensity for small-head-size total hip arthroplasty.

OBJECTIVE: Examine the role of surgical orientation of the acetabular cup on posterior dislocation propensity for small-head-size total hip arthroplasty. DESIGN: A finite element model of a widely used total hip arthroplasty system was examined for peak resisting moment and range-of-motion prior to impingement, as well as prior to onset of posterior dislocation. Acetabular component surgical orientation was varied. BACKGROUND: Dislocation is a leading cause of total hip replacement failure, with an incidence between 2% and 11%. Clinical registries imply acetabular component orientation to be a leading predictor of dislocation. The finite element method permits this complex kinetic behavior to be addressed systematically. METHODS: Twenty-five combinations of cup abduction (five angles) and anteversion (five angles) were studied, with the resultant resisting moment about the cup center being tracked in each case. Key events were benchmarked, and a novel dislocation resistance index was developed for multi-factor comparison. RESULTS: Increasing tilt and/or anteversion resulted in a monotonically increasing range-of-motion prior to impingement, as well as increased peak resisting moment. Range of motion was more sensitive to tilt, while peak resisting moment was more sensitive to anteversion. Peak resisting moment for 22-mm head size was nearly 25% less than that for a 26-mm head. CONCLUSIONS: Increased cup tilt and anteversion discourage posterior dislocations of small-head-size components. RELEVANCE: Pre-existing soft tissue compromise and untoward patient motions/postures are largely beyond surgeon control. However, other factors being equal, especially for small-head-size components, many posterior dislocations that would otherwise occur might be prevented by suitable tilt and anteversion of the acetabular component.

Acetabulum↗
PubMed2002

A new animal model of femoral head osteonecrosis: one that progresses to human-like mechanical failure.

Existing animal models of femoral head osteonecrosis, while displaying varying levels of concordance with early histopathologic features of the human disorder, generally fail to progress to end-stage mechanical collapse. A new animal model of osteonecrosis is here introduced, utilizing the emu (Dromaius novaehollandie). These animals' bipedality and their high activity level represent a much more challenging biomechanical environment to the hip than seen in quadrupedal models of this disorder. Femoral head osteonecrosis was induced surgically, using a combination of ischemic (vessel ligation) and cryogenic (liquid nitrogen) insults. Of nineteen emus allowed free-roaming pen activity to study the natural history of such lesions, eighteen progressed to an osseous structural failure, sixteen of them developing incapacitating lameness at an average time point 11.75 weeks after the surgical insult. Histologically, the animals showed close concordance with both the early- and late-stage human pathology, in six cases even to the point of developing a crescent sign. Because of its large physical size and its consistent progression to mechanical collapse, the emu appears to offer a unique opportunity for the near-human-scale study of surgical interventions to forestall femoral head collapse. Toward this end, various directions for model refinement are outlined.

Animals↗
PubMed2002

Reliability of detecting prosthesis/cement interface radiolucencies in total hip arthroplasty.

A laboratory study assessed the reliability of detecting radiolucencies at the prosthesis/cement interface in femoral components for total hip replacement. Radiolucencies (thicknesses = 0.1, 0.3, 0.5 and 0.7 mm) were created by randomly masking non-tip Gruen zones (six per stem) in a group of 72 matte-finish femoral components. Only half of all Gruen zones were masked. The femoral components were reproducibly implanted in composite fiberglass replicate femurs. Anteroposterior and lateral radiographs taken using conventional techniques were then presented to 10 experienced readers, who scored each of 432 non-tip Gruen zones for radiolucency presence or absence. The series-average radiolucency detection rate was 47.1%, with a breakdown of 9.8%, 20.7%, 69.8% and 88.0, for radiolucency thicknesses of 0.1, 0.3, 0.5 and 0.7 mm, respectively. The false positive rate was 7.5%. The findings argue strongly that in many or most instances, initial cement-prosthesis debonding is not reliably detected from conventional plain film radiographs. Radiolucencies of at least 0.7 mm width are necessary to be accurately detectable by most viewers.

Arthroplasty, Replacement, Hip↗
PubMed2002

Polyethylene liner cementation into fixed acetabular shells.

A patient presenting with a secure cementless acetabular component and with femoral head penetration through the polyethylene liner is a common clinical problem. Cementing a new liner into the fixed shell is one option. We evaluated this option in a clinical series of 17 cases and with a preliminary mechanical study. In the 1 clinical failure (5.9%), the failure occurred at the cement-liner interface. The most important variable in optimizing the mechanical strength of the cemented liner construct was adequate preparation of the cement-liner interface. This approach to treating the patient with a fixed cementless shell and a worn polyethylene liner can provide a durable construct with minimal morbidity.

Aged↗
PubMed2002

A voxel-based formulation for contact finite element analysis.

To date, voxel-based finite element models have not been feasible for contact problems, owing to the inherent stair-step boundary discontinuities. New preprocessing techniques are reported herein to mesh these boundaries smoothly, for purposes of contact stress analysis. Further, new techniques are reported to concentrate the mesh resolution automatically near the articular surface, thus reducing the problem size to levels compatible with executing nonlinear problems on contemporary engineering workstations. Close approximations to Hertzian analytical solutions were obtained for spherical and cylindrical geometries meshed in this manner, and an illustrative anatomical contact problem of the human hip joint is presented.

Computer Simulation↗
PubMed2002

Choices and compromises in the use of small head sizes in total hip arthroplasty.

Observation cohort studies, a sliding-distance-coupled finite element model, and an expanded finite element model that simulates dislocation were used to evaluate the benefits and compromises associated with the use of smaller femoral heads in the total hip arthroplasty construct. Wear studies of total hip arthroplasty cohorts showed less polyethylene wear and less deleterious effects of third body debris when smaller femoral head sizes were used. The sliding-distance-coupled finite element model findings were corroborated by these clinical wear studies. The dislocation model predicted the increased propensity for dislocation when smaller modular head femoral components were used in the cohort studies. Impingement is not the only contributor to frank dislocation. The dislocation model explicitly defined the range of motion changes from impingement to dislocation, and the resisting moment changes between construct designs.

Adult↗
PubMed2002

Fractures of the olecranon: an in vitro study of elbow joint stresses after tension-band wire fixation versus proximal fracture fragment excision.

BACKGROUND: Displaced fractures of the olecranon usually require operative treatment, by either open reduction with internal fixation (ORIF) or excision of the proximal fragment. However, the relative merits of these treatment options have not been fully delineated. One treatment outcome measure of joint function is residual intra-articular stress. The purpose of this study was to evaluate the effect of these two types of olecranon fracture treatment on humeroulnar joint stress. METHODS: Eight matched pairs of fresh frozen cadaveric upper extremities were thawed; stripped of skin, muscular, and neurovascular tissue; and potted in polymethylmethacrylate. The intra-articular humeroulnar joint peak pressures were measured at 90 degrees of elbow flexion using pressure-sensitive film after application of a 0.15 kg-m torque through the remaining triceps muscle attachment. First, pretreatment (normal) pressures were obtained from the major contact regions of the humeroulnar joint. A 50% olecranon osteotomy was then performed simulating a fracture, and the elbows from each of the paired specimens were randomly assigned to one or the other of two treatment groups: ORIF (using a tension-band wiring technique) and proximal fragment excision. Joint pressures were remeasured. A two-tailed paired t test was used for statistical analysis. RESULTS: After osteotomy, the peak pressures were higher, overall, in the excision group. Comparing each posttreatment experimental group to its pretreatment (normal) counterpart revealed that the peak pressures in the distal medial and distal lateral articular subzones were significantly higher for the fragment excision group (p = 0.005 and p= 0.0008, respectively), but were not significantly different in the ORIF group (p = 0.545 and p= 0.153, respectively). CONCLUSION: The findings of this study indicate that ORIF restores the normal biomechanics of the elbow joint and proximal fragment excision results in abnormally elevated joint stresses. These elevated joint stresses may, over time, contribute to the development of elbow pain and osteoarthrosis. Therefore, ORIF should continue to be regarded as the treatment of choice for displaced fractures of the olecranon involving large proximal fracture fragments similar in size to those in this study.

Biomechanical Phenomena↗
PubMed2002

Local head roughening as a factor contributing to variability of total hip wear: a finite element analysis.

Large inter-patient variability in wear rate and wear direction have been a ubiquitous attribute of total hip arthroplasty (THA) cohorts. Since patients at the high end of the wear spectrum are of particular concern for osteolysis and loosening, it is important to understand why some individuals experience wear at a rate far in excess of their cohort average. An established computational model of polyethylene wear was used to test the hypothesis that, other factors being equal, clinically typical variability in regions of localized femoral head roughening could account for much of the variability observed clinically in both wear magnitude and wear direction. The model implemented the Archard abrasive/adhesive wear relationship, which incorporates contact stress, sliding distance, and (implicitly) bearing surface tribology. Systematic trials were conducted to explore the influences of head roughening severity, roughened area size, and roughened area location. The results showed that, given the postulated wear factor elevations, head roughening variability (conservatively) typical of retrieval specimens led to approximately a 30 degrees variation in wear direction, and approximately a 7-fold variation in volumetric wear rate. Since these data show that randomness in head scratching can account for otherwise-difficult-to-explain variations in wear direction and wear rate, third-body debris may be a key factor causing excessive wear in the most problematic subset of the THA population.

Acetabulum↗