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Thomas D Brown

Publications and source records attributed to Thomas D Brown.

At least 37 records · Page 2Linked to original sources
PubMed2005

A laboratory simulation for morselized bone graft fusion: apparent modulus under operatively based femoral impaction kinetics.

The purpose of this study was to determine the apparent modulus changes accompanying a novel procedure for simulating in situ fusion of morselized cancellous bone femoral impaction grafts. An experienced surgeon's habitual intra-operative impaction grafting protocol was first quantified in human cadaver femurs, using a customized impulse force hammer. A corresponding standardized impaction procedure was then defined, and was used to prepare impaction grafts in axisymmetric metallic fixturing designed to replicate the nominal geometry of femoral canal confinement. Impaction graft fusion was simulated by mixing morselized cancellous bone with an amine-based epoxy adhesive before the impaction, then allowing the mixture to fuse after the impaction (J. Biomech. 34 (2001) 811). Force/deflection behavior of the unfused and fused impaction grafts was measured for both the (tapered) proximal and (untapered) distal portions of the grafts. Apparent modulus was then calculated from force/deflection stiffness. The impaction graft fusion simulation increased apparent modulus by an order of magnitude over the unfused state, for mixture parameters appropriate to have the fused graft apparent modulus be comparable to the compressive modulus of intact femoral cancellous bone.

Arthroplasty, Replacement, Hip↗
PubMed2005

Kinetically critical sites of femoral head roughening for wear rate acceleration in total hip arthroplasty.

Polyethylene wear acceleration from (scratching) damage to the femoral head is a recognized hazard from constructs prone to generate third-body debris, but the phenomenon is nebulous and therefore often is subordinated to more direct and immediate considerations. To help delineate tangible quantitative relationships between counterface roughening and accelerated polyethylene wear, an experimentally validated sliding-distance-coupled finite element model of total hip replacement wear was adapted to incorporate regions of localized femoral head roughening. This computational formulation was used systematically to identify the sites on the femoral head for which a given severity of local roughening (parameterized in terms of roughening patch size and tribologic wear coefficient) was most consequential in terms of elevated polyethylene wear. Two such sites, of nominally comparable kinetic importance, were consistently evident throughout a wide range of roughening severities. These critical sites were located quasi-superiorly near the sagittal midline of the head, one slightly anterior and one slightly posterior of the coronal midline.

Arthroplasty, Replacement, Hip↗
PubMed2005

Tensile engagement of the peri-ankle ligaments in stance phase.

BACKGROUND: Development of reconstructive operative procedures to restore normal ankle kinematics after injury requires an understanding of the biomechanics of the ankle during gait. The contribution of the peri-ankle ligaments to ankle motion control is not yet well understood. Knowledge of the tensile engagement of the peri-ankle ligaments during stance phase is necessary to achieve physiologic motion patterns. METHODS: Eleven fresh-frozen cadaver ankles were subjected to a dynamic loading sequence simulating the stance phase of normal level gait. Simultaneously, ligament strain was continuously monitored in the anterior talofibular, calcaneofibular, and posterior talofibular ligaments, as well as in the anterior, middle, and posterior superficial deltoid ligaments. Eight of these specimens underwent further quasi-static range-of-motion testing, where ligament tension recruitment was assessed at 30 degrees plantarflexion and 30 degrees dorsiflexion. RESULTS: In the dynamic loading tests, none of the ligaments monitored showed a reproducible strain pattern indicating a role in ankle stabilization. However, in the extended range-of-motion tests, most ligaments were taut in plantarflexion or dorsiflexion. CONCLUSIONS: A consistent combination of individual ligament strain patterns that principally control ankle motion was not identified; none of the ligaments studied were reproducibly recruited to be a primary stabilizing structure. The peri-ankle ligaments are likely to be secondary restraining structures that serve to resist motion to avoid extreme positions. Stance phase ankle motion appears to be primarily controlled by articular congruity, not by peri-ankle ligament tension.

Aged↗
PubMed2004

Interfragmentary surface area as an index of comminution severity in cortical bone impact.

A monotonic relationship is expected between energy absorption and fracture surface area generation for brittle solids, based on fracture mechanics principles. It was hypothesized that this relationship is demonstrable in bone, to the point that on a continuous scale, comminuted fractures created with specific levels of energy delivery could be discriminated from one another. Using bovine cortical bone segments in conjunction with digital image analysis of CT fracture data, the surface area freed by controlled impact fracture events was measured. The results demonstrated a statistically significant (p < 0.0001) difference in measured de novo surface area between three specimen groups, over a range of input energies from 0.423 to 0.702 J/g. Local material properties were also incorporated into these measurements via CT Hounsfield intensities. This study confirms that comminution severity of bone fractures can indeed be measured on a continuous scale, based on energy absorption. This lays a foundation for similar assessments in human injuries.

Animals↗
PubMed2004

Cartilage thickness in cadaveric ankles: measurement with double-contrast multi-detector row CT arthrography versus MR imaging.

PURPOSE: To test the accuracy of double-contrast multi-detector row computed tomographic (CT) arthrography for measurement of cartilage thickness in cadaveric ankles and to compare this technique with three-dimensional (3D) fat-suppressed spoiled gradient-echo in the steady state (FS-SPGR) magnetic resonance (MR) imaging. MATERIALS AND METHODS: Five cadaveric ankles were used. In the ankle specimens, five to nine 1.5-mm-diameter holes were drilled across the joint traversing the tibial subchondral bone, tibial articular cartilage, talar dome cartilage, and talar subchondral bone. The ankle specimens were obtained and used according to institutional policies. Each ankle specimen was imaged first by using 3D FS-SPGR MR imaging with a 1.5-T magnet and then by using double-contrast arthrography followed by CT with a four-detector row scanner (ie, double-contrast multi-detector row CT arthrography). The section thickness used for CT scanning was 1.0 mm reconstructed in 0.5-mm intervals. The MR and CT images obtained in the five specimens were then downloaded to a workstation, where a measurement tool was used to measure the cartilage thickness at each hole. The physical measurement of cartilage thickness at each hole was used as the reference standard with which the MR imaging and CT measurements were compared. Linear regression and correlation analyses were performed by using a statistical computer program. RESULTS: Double-contrast arthrography followed by multi-detector row CT, as compared with 3D FS-SPGR MR imaging, enabled more accurate measurement of the physical cartilage thickness in the ankle (P < .001). CONCLUSION: In this study of five cadaveric ankles, multi-detector row CT arthrography was more accurate than 3D FS-SPGR MR imaging for measurement of articular cartilage thickness in the ankle.

Adult↗
PubMed2004

Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma.

BACKGROUND: The goal of the current study was to evaluate the efficacy and toxicity of capecitabine in patients with nonresectable hepatobiliary carcinoma. METHODS: The authors performed a retrospective analysis of all patients with hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), or gallbladder carcinoma (GBC) who were ever treated with oral capecitabine. The medical records of 116 patients with hepatobiliary carcinoma who were treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX) between July 1998 and March 1999 were reviewed. RESULTS: A total of 63 patients were treated with capecitabine (37 with HCC, 18 with CCA, 8 with GBC). Capecitabine 1000 mg/m(2) was administered twice daily for 14 days. Treatment was repeated every 21 days. Each patient received 1-15 treatment cycles. Nine patients (14%)-11% of patients with HCC, 6% of patients with CCA, and 50% of patients with GBC-had either a complete response (CR) or a partial response. A CR was radiologically confirmed in one patient with HCC and in two patients with GBC. The median survival times were 10.1 months (95% confidence interval [CI], 4.5-15.7 months) for patients with HCC, 8.1 months (95% CI, 7.4-8.9 months) for patients with CCA, and 9.9 months (95% CI, 4.4-15.4 months) for patients with GBC. The most common toxicity was hand-foot syndrome (37%). Grade 3 thrombocytopenia occurred in 8% of patients with HCC. No other significant toxicities were observed. For all patients, response to treatment was positively correlated with survival and decline in tumor markers. CONCLUSIONS: Capecitabine was found to be safe for patients with hepatobiliary carcinoma, including those with cirrhosis. The antitumor activity of single-agent capecitabine was most pronounced in patients with GBC, was modest in patients with HCC, and was poor in patients with CCA.

Administration, Oral↗
PubMed2004

Osteocyte-based image analysis for quantitation of histologically apparent femoral head osteonecrosis: application to an emu model.

Femoral head osteonecrosis is often characterized histologically by the presence of empty lacunae in the affected bony regions. The shape, size and location of a necrotic lesion influences prognosis, and can, in principle, be quantified by mapping the distribution of empty lacunae within a femoral head. An algorithm is here described that automatically identifies the locations of osteocyte-filled vs. empty lacunae. The algorithm is applied to necrotic lesions surgically induced in the emu, a large bipedal animal model in which osteonecrosis progresses to collapse, as occurs in humans. The animals' femoral heads were harvested at sacrifice, and hematoxylin and eosin-stained histological preparations of the coronal midsections were digitized and image-analyzed. The algorithm's performance in detecting empty lacunae was validated by comparing its results to corresponding assessments by six trained histologists. The percentage of osteocyte-filled lacunae identified by the algorithm vs. by the human readers was statistically indistinguishable.

Algorithms↗
PubMed2004

Incongruity versus instability in the etiology of posttraumatic arthritis.

The etiology of posttraumatic arthritis is understood poorly but it clearly has a pathomechanical component. Posttraumatic arthritis likely results from irreversible cartilage damage sustained at the time of injury and chronic cartilage overloading resulting from articular incongruity and instability. However, the relative importance of instability and incongruity is unknown. Clinical studies show that the hip, knee, and ankle tolerate incongruity differently. However, all three joints poorly tolerate instability. Basic mechanical studies have shown that static loading of articular surface incongruities have caused relatively modest increases in contact pressure. However, static testing poorly replicates normal viscoelastic properties of cartilage, which may mask important transient stress elevations that occur during motion. Static tests also ignore potential abnormal loads that may accumulate throughout a motion cycle. We review the clinical and basic scientific evidence linking incongruity and instability to posttraumatic arthritis. Preliminary data from a newly developed dynamic ankle testing device are presented. Dynamic testing allows measurement of transient contact loads and loading rates that occur through the entire motion cycle and it opens the door to measure mechanical abnormalities associated with instability.

Ankle Injuries↗
PubMed2004

New methods for assessing cartilage contact stress after articular fracture.

Progress in reducing the incidence and severity of posttraumatic arthritis depends in part on avoiding deleterious stress levels at residual local incongruities. Systematic efforts to elucidate factors adversely influencing cartilage's mechanical environment in turn depend on the availability of suitable modalities to assess intraarticular contact stresses. This has been and remains a challenging biomechanical problem. Technologic approaches used in the past have included mathematical analyses and indwelling physical sensors, each with advantages and limitations. Two emerging, mutually complementary capabilities show promise of dramatically altering the state of the art in this important field. The first of these methodologies, voxel-based contact finite element analysis, provides accurate computational estimates of cartilage stress on a patient-specific basis, and does so while accommodating arbitrarily idiosyncratic patterns of local articular incongruity. The second methodology, instrumentational, involves transient pressure distribution recordings using specially designed piezoresistive array sensors. Operational considerations for both of these new assessment technologies are described, and promising directions for future development are outlined.

Biomechanical Phenomena↗
PubMed2004

Pathomechanic determinants of posttraumatic arthritis.

The etiology of posttraumatic arthritis is poorly understood. One possible mechanism involves a mechanical insult to the cartilage matrix that affects chondrocyte function. To better understand the etiology of posttraumatic arthritis, pathomechanic changes in articular contact mechanics resulting from injury during physiologic motion and loading need to be determined. Previous studies of injury-associated changes in articular contact mechanics, using static testing methods, have measured relatively modest increases in contact stresses. Static testing cannot measure transient loads associated with motion or loading rates. This testing method poorly simulates normal viscoelastic cartilage properties, and accounts for contact stress changes in a single or limited number of joint positions. In this study, time-variant contact stresses in two ankles with an anterolateral stepoff were measured during quasiphysiologic motion and loading. Contact stresses were integrated over the entire range of motion to estimate pathomechanic loads that accumulate over the entire motion cycle. Numerical techniques were applied to time-variant contact stress data to calculate contact stress directional gradients and contact stress rates of change. Contact stress directional gradients and rates of change were integrated over the complete motion cycle to estimate whole-cycle accumulation of these potential pathomechanic parameters.

Ankle Injuries↗
PubMed2004

Chondrocyte senescence, joint loading and osteoarthritis.

cellular level is not completely understood, but both aging and loading-induced stresses have been shown to undermine cell functions related to the maintenance and restoration of the cartilage matrix. Based on precedents set by studies of other age-related degenerative diseases, we have focused our laboratory work on senescence as the cause of age-dependent decline in chondrocytes and on the impact of excessive mechanical stresses in promoting senescence. We hypothesized that senescent chondrocytes accumulate with age in articular cartilage and we propose that excessive mechanical stress plays a role in this process by promoting oxidative damage in chondrocytes that ultimately causes them to senesce. To test this hypothesis, we measured cell senescence markers (beta-galactosidase expression, mitotic activity, and telomere length) in human articular cartilage chondrocytes, and determined the effects of chronic exposure to oxidative stress on chondrocyte growth and senescence. In addition, we measured the effects of abnormally high levels of mechanical shear stress on the release of oxidants in cartilage explants. We found that senescent chondrocytes accumulated with age in articular cartilage. In vitro studies showed that chronic oxidative stress caused by repeated exposure to peroxide, or by growth under superphysiologic oxygen tension caused chondrocyte populations to senesce prematurely, before extensive telomere erosion occurred. Mechanical shear stress applied to cartilage explants considerably increased the production of oxidants. These observations support the hypothesis that senescence accounts for age-related decline in chondrocyte function and indicate that mechanically induced oxidative damage plays a role in this process. This suggests that new efforts to prevent the development and progression of osteoarthritis should include strategies that slow the progression of chondrocyte senescence or replace senescent cells.

Adolescent↗
PubMed2004

The role of the interosseous talocalcaneal ligament in subtalar joint stability.

BACKGROUND: Injury of the interosseous talocalcaneal ligament (ITCL) has been recognized as a cause of subtalar instability, though lack of an accepted clinical test has limited the ability of clinicians to reliably make the diagnosis. Clinical effects of ITCL failure remain unclear because of insufficient understanding of the role of the ligament. METHODS: Load-displacement characteristics of the subtalar joint were studied in six cadaver specimens using an axial distraction test and a transverse multi-direction drawer test. In all tests, cyclic loading (+/-60 N) was applied, and load-displacement responses were collected before and after sectioning of the ITCL. Two parameters were used to analyze the data: neutral-zone laxity as a measure of joint play, and flexibility as a measure of resistance to applied force. RESULTS: In the axial distraction test, sectioning increased both neutral-zone laxity and flexibility (p =.01 and.02, respectively). In the transverse test, sectioning caused increase of both neutral-zone laxity and flexibility (p <.001, for each). Neutral-zone laxity increased most greatly along an axis defined roughly by the posterior aspect of the fibula and the central region of the medial malleolus. Flexibility increased most in the medial direction (p <.05, for each). CONCLUSIONS: Results confirmed the role of the ITCL in maintaining apposition of the subtalar joint, as well as suggested its role in stabilizing the subtalar joint against drawer forces applied to the calcaneus from lateral to medial. The dominant direction of increased neutral-zone laxity described above suggests the optimal direction for detecting subtalar instability involved with ITCL injury. CLINICAL RELEVANCE: ITCL failure may result in subtalar instability and should be examined with a drawer force along the preferential axis roughly from the posterior aspect of the fibula to the central region of the medial malleolus. Further clinical evaluation is required to determine whether ITCL failure is reliably detectable.

Adult↗
PubMed2004

Joint injury, repair, and remodeling: roles in post-traumatic osteoarthritis.

Joint injuries, especially intraarticular fractures, frequently lead to progressive joint degeneration that causes the clinical syndrome of posttraumatic osteoarthritis. Orthopaedists try to prevent this disease by attempting to restore joint congruity, alignment, and stability; however, many patients have crippling joint pain and dysfunction develop despite optimal current treatment. The pathophysiology of posttraumatic osteoarthritis has not been explained. It is not simply the magnitude and type of injury that determines whether an injured articular surface will repair and remodel or undergo progressive degeneration. For these reasons, clinically significant progress in preventing posttraumatic osteoarthritis depends on advances in understanding of the pathogenesis of this disease that will make it possible to decrease the risk of articular surface degeneration and facilitate articular surface repair and remodeling. We examine the relationships between joint injury, repair and remodeling, and joint degeneration; the factors that increase the risk of posttraumatic joint degeneration; and, the questions that need additional investigation to develop treatments of joint injuries that will decrease the risk or severity of posttraumatic osteoarthritis.

Bone Remodeling↗
PubMed2004

Implementing capsule representation in a total hip dislocation finite element model.

Previously validated hardware-only finite element models of THA dislocation h ave clarifiedhow various component design and surgical placement variables contribute to resisting the propensity for implant dislocation. This body of work has now been enhanced with the incorporation of experimentally based capsule representation, and with anatomic bone structures. The current form of this finite element model provides for large deformation multi-body contact (including capsule wrap-around on bone and/or implant), large displacement interfacial sliding, and large deformation (hyperelastic) capsule representation. In addition, the modular nature of this model now allows for rapid incorporation of current or future total hip implant designs, accepts complex multi-axial physiologic motion inputs, and outputs case-specific component/bone/soft-tissue impingement events. This soft-tissue-augmented finite element model is being used to investigate the performance of various implant designs for a range of clinically-representative soft tissue integrities and surgical techniques. Preliminary results show that capsule enhancement makes a substantial difference in stability, compared to an otherwise identical hardware-only model. This model is intended to help put implant design and surgical technique decisions on a firmer scientific basis, in terms of reducing the likelihood of dislocation.

Arthroplasty, Replacement, Hip↗
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↗