Search PubMed⌕ Search

Biomedical subjects

T D Brown

Publications and source records attributed to T D Brown.

At least 19 recordsLinked to original sources
PubMed1999

Articulated external fixation of the ankle: minimizing motion resistance by accurate axis alignment.

This study describes how an optimal single hinge axis position can be established for the application of articulated external fixation to the ankle joint. By deliberately introducing various amounts of relative mal-alignment between the optimal talocrural joint axis and the actual fixator hinge axis, it was possible to measure the corresponding amounts of additional resistance to joint motion. In a cadaveric study of six ankle specimens, we determined the instant axis of rotation of the talocrural joint from 3-D kinematic data. acquired by an electromagnetic motion tracking system. For each specimen, an optimal fixator hinge position was calculated from these motion data. Compared to the intact natural joint, aligning the fixator along the optimized axis position caused a moderate increase in energy (0.14 J) needed to rotate the ankle through a prescribed plantar/dorsiflexion range. However, malpositioning the hinge by 10 mm caused more than five times that amount of increase in motion resistance. While articulated external fixation with limited internal fixation can establish a favorable environment for the repair of severe injuries such as tibial pilon fractures, the large additional resistance to motion accompanying a malpositioned fixator axis suggests the development of untoward intra-articular forces that could act to disturb fragment alignment.

Ankle↗
PubMed1999

Periprosthetic fractures of the acetabulum.

Periprosthetic acetabular fractures during and after total hip replacement occur infrequently. Intraoperative fractures have risen with the use of press fit cementless fixation techniques and postoperative fractures are increasing because of the long-term problems associated with osteolysis. This article outlines the classification and management of these fractures.

Acetabulum↗
PubMed1999

Activity of a purified His-tagged 3C-like proteinase from the coronavirus infectious bronchitis virus.

Previous studies in vitro of the processing of cloned polyprotein fragments from the coronavirus infectious bronchitis virus (IBV) large open reading frame (ORF1), confirmed the activity of a predicted 3C-like proteinase (3CLP) domain and suggested that the proteinase is released autocatalytically from the polyprotein in the form of a 35 kDa protein, 3CLpro, capable of further cleavages in trans. In order to identify such cleavages within the ORF1 polyprotein mediated by 3CLpro, the proteinase was expressed in bacteria, purified and used in trans cleavage assays with polyprotein fragments lacking the 3CLP domain as targets. The proteinase was expressed as a polyprotein fragment which was able to process during expression in bacterial cells, releasing mature 3CLpro. A histidine (His6) tag was introduced close to the C-terminus of the proteinase to aid purification. Processing demonstrated by the tagged proteinase was indistinguishable from that of the wild-type enzyme indicating that the site chosen for the tag was permissive. From these studies we were able to demonstrate trans cleavages consistent with the use of most of the previously predicted or identified sites within the open reading frame of gene 1. This tentatively completes the processing map for the ORF1 region with respect to 3CLpro.

Animals↗
PubMed1999

Avian encephalomyelitis virus is a picornavirus and is most closely related to hepatitis A virus.

The complete RNA genome of avian encephalomyelitis virus (AEV) has been molecularly cloned and sequenced. This revealed AEV to be a member of the Picornaviridae and consequently it is the first avian picornavirus for which the genome has been sequenced. Excluding the poly(A) tail the genome comprises 7032 nucleotides, which is shorter than that of any mammalian picornavirus sequenced to date. An open reading frame commencing at nucleotide 495 and terminating at position 6896 (6402 nucleotides) potentially encodes a polyprotein of 2134 amino acids. The polyprotein sequence has 39% overall amino acid identity with hepatitis A virus (HAV; genus Hepatovirus), compared to 19 to 21% for viruses from the other five picornavirus genera. Eleven cleavage products were predicted. The highest identity (49%) with HAV was in the P1 region, encoding the capsid proteins. The 5' and 3' untranslated regions (UTRs) comprise 494 and 136 nucleotides, respectively. The 5' UTR is the shortest of any picornavirus sequenced to date and, unlike HAV, it does not contain a long polypyrimidine tract.

Amino Acid Sequence↗
PubMed1998

Mechanical behavior of human morselized cancellous bone in triaxial compression testing.

Despite its widespread use as graft material in orthopaedic surgical procedures, morselized cancellous bone has not yet been well characterized from the standpoint of its mechanical properties. To accommodate the noncohesive nature of this loose particulate form of bone, a triaxial compression test apparatus commonly used in engineering soil mechanics was adapted for the testing of fresh-frozen human morselized cancellous bone specimens. Triaxial compression tests were run to 30% axial strain at five different levels of confining pressure ranging from 0.276 to 0.552 MPa. The measured axial stress versus axial strain behavior was bimodal, characterized initially by relatively stiff linear behavior, then by a rapid transition to a much more compliant (but, again, approximately linear) domain until test cessation. The apparent axial moduli of both response regions were found to be nearly linear functions of the transverse confining pressure. As typically prepared surgically, the distribution of particle size was found to have approximately 80% of the bone graft, by weight, encompassed in particles 0.42-3.2 mm in size. Triaxial tests of samples segregated by size showed that particle size had no appreciable effect on apparent material properties. The nominal Young's modulus and Poisson's ratio of morselized cancellous bone were 100 MPa and 0.2, respectively.

Biomechanical Phenomena↗
PubMed1998

Prediction of long-term polyethylene wear in total hip arthroplasty, based on early wear measurements made using digital image analysis.

The capability to reliably predict long-term in vivo wear of polyethylene would be of great value for the early identification of problematic total hip designs. Formal quantitative estimates of long-term polyethylene wear were made from a series of 197 patients who had a total hip arthroplasty and who were followed for a minimum of 10 years; the estimates were based on the wear that was apparent radiographically at nominally 2 years after the operation. A newly developed digital image-analysis edge-detection procedure was applied to 1,237 archived follow-up radiographs. The edge-detection measurements were analyzed with a robust regression random-coefficients statistical formulation developed especially to address the distributions of wear rate observed across this population over time. Formal regression equations were reported, which can be used to estimate late-wear depth for a patient radiographed at a 2-year follow-up visit. Series wide, the correlation between predicted and observed wear depths was 0.73 at 4 years, with a correlation decline of approximately 0.03 per additional year.

Aged↗
PubMed1998

Proteolytic processing of the polyprotein encoded by ORF1b of the coronavirus infectious bronchitis virus (IBV).

We present here evidence demonstrating that four previously predicted Q-S(G) cleavage sites, encoded by the IBV sequences from nucleotide 15,129 to 15,134, 16,929 to 16,934, 18,492 to 18,497, and 19,506 to 19,511, respectively, can be recognised and transcleaved by the 3C-like proteinase. Five mature products with sizes of approximately 100 kDa, 65 kDa, 63 kDa, 42 kDa and 35 kDa are released from the ORF1b polyprotein by the 3C-like proteinase-mediated cleavage at these positions. Meanwhile, expression of plasmids containing only the ORF1b region showed no autocleavage of the polyprotein encoded, suggesting that the 3C-like proteinase may be the sole proteinase involved in processing of the 1b polyprotein. These data may therefore represent a complete processing map of the polyprotein encoded by ORF1b of mRNA1.

Antibodies↗
PubMed1998

Sequence elements involved in the rescue of IBV defective RNA CD-91.

Deletion mutagenesis has been used to identify essential regions for rescue of coronavirus defective RNAs (D-RNAs). Using this technique on a cloned IBV D-RNA CD-91, we have identified a region potentially important in its rescue. Comparing the sequence of D-RNAs rescued with those not rescued we have deduced that a 72 base region corresponding to base number 13,824 to 13,896 in the viral genome is required for rescue. This may be an IBV D-RNA packaging signal or a cis-acting element involved in replication. Further experiments and modification of our techniques will be required to differentiate between the two processes.

Animals↗
PubMed1998

Pharmacokinetic and phase I studies of brequinar (DUP 785; NSC 368390) in combination with cisplatin in patients with advanced malignancies.

Brequinar (DUP 785; NSC 368390) is a quinoline carboxylic acid derivative that inhibits pyrimidine synthesis at the level of dihydro-orotate dehydrogenase and revealed synergy with cisplatin in preclinical models. In this study investigating the pharmacokinetic and toxicity of brequinar in combination with cisplatin, patients were initially treated with weekly brequinar, in combination with an every-three-week administration of cisplatin. Due to toxicity, the schedule was modified to a 28-day cycle with brequinar given on days 1, 8, 15, and cisplatin on day 1. A total of 24 patients (16 male, 8 female; median age 57; median performance status 1) received 69 courses of therapy. Six dose levels were explored, with cisplatin/ brequinar doses, respectively, of 50/500, 50/650, 50/860, 60/860, 75/650, and 75/860 mg/m2. The serum concentration versus time curves for brequinar were biphasic. A comparison of the pharmacokinetic results after the first and third doses of brequinar indicate that the presence of 50, 60, and 75 mg/m2cisplatin did not change the protein binding and the pharmacokinetics of brequinar in any of the three brequinar-dose groups. Total cisplatin plasma pharmacokinetic followed a triphasic-shape curve and unbound cisplatin decayed at a very rapid rate. Since pharmacokinetic parameters for total cisplatin in this study were similar to those reported in the literature, the presence of brequinar is unlikely to alter the pharmacokinetics of cisplatin. Main dose-limiting toxicities included myelosuppression (including neutropenia and thrombocytopenia) and mucositis. Cisplatin/brequinar doses of 50/500, 50/650, 50/860, 60/860, 75/650, and 75/860 mg/m2, were associated with dose limiting toxicity in 0/3, 1/3, 1/3, 1/3, 2/4, 2/5, and 4/6 patients, respectively. This study shows that co-administration of brequinar and cisplatin does not affect the pharmacokinetic properties of either drug and that the MTDs of cisplatin/brequinar combinations are 60/860 mg/m2 or 75/650 mg/m2. From this study, we conclude that full dose of 75 mg/m2 cisplatin (day 1) can be administered with 650 mg/m2 brequinar (days 1, 8 and 15) without significant modifications of individual drug pharmacokinetic parameters.

Adolescent↗
PubMed1998

Loading paradigms--intentional and unintentional--for cell culture mechanostimulus.

Recent interest in the response of cells or tissues to mechanical stimuli has led to the introduction of a variety of laboratory devices designed to deliver quantified mechanical inputs to culture systems. Such devices commonly rely upon distention of a flexible culture substrate, achieved either by direct platen abutment or by transmural pressure differentials. Unfortunately, the substrate distentions in such systems are often unintentionally nonuniform, and typically also induce motions in the overlying liquid nutrient medium--motions which in turn exert unintended reactive stresses upon the culture layer. In order to characterize the nature of these reactive fluid stresses, computer models have been developed for the nutrient medium flow fields (ie, the velocity and pressure distributions) for three established contemporary cell culture mechanostimulus systems. Temporal and spatial distributions of reactive normal and shear stresses are reported for typical duty cycles in these respective instruments.

Cell Culture Techniques↗
PubMed1998

A finite element analysis of factors influencing total hip dislocation.

A previously validated three-dimensional finite element model was used to study how several total hip component design and surgical placement variables contribute to resisting the propensity for posterior dislocation in the case of leg crossing in an erectly seated position. The computational formulation incorporated treatments of polyethylene material nonlinearity and large displacement sliding contact. The primary outcome measures were the peak intrinsic moment developed to resist dislocation, and the ranges of motion before neck on lip impingement and before frank dislocation. Modifications of the acetabular linear design (chamfer bevel angle, lip breadth, head center inset) involved trading off improved peak resisting moment for compromised range of motion and vice versa. Increases of head size led to substantial improvements in peak resisting moment, but if the head to neck diameter ratio was held constant, had almost no influence on the component range of motion. For the leg crossing event studied, increased component anteversion, and even more so increased tilt (less net abduction), achieved improvements in range of motion and in peak resisting moment, but these changes imply diminished resistance to anterior dislocation from extension and adduction motion inputs.

Arthroplasty, Replacement, Hip↗
PubMed1998

Salvage of total hip instability with a constrained acetabular component.

Between April 1988 and February 1993, 101 constraining acetabular components were implanted into 98 patients. One patient was lost to followup at 8 months. Otherwise, all patients were observed until death or for at least 2 years minimum followup. The average clinical followup for the living patients was 61 months (range, 24-97 months). Indications for the use of the constrained acetabular components were recurrent dislocation (an average of six dislocations, range 2-20) in 56 cases, intraoperative instability in 38 cases, and neurologic impairment in seven cases. For the entire group there were four cases of recurrent dislocation or failure of the component (4%). For the cases where this component was used for recurrent dislocation, 96% (54 of 56 cases) had no additional dislocations. Radiographically, at this short term followup, there was no evidence of an increased incidence of femoral or acetabular component loosening. The authors recommend judicious use of this component as a salvage measure for desperate cases of hip instability during or after total hip arthroplasty.

Acetabulum↗
PubMed1998

Factors influencing accuracy of screw displacement axis detection with a D.C.-based electromagnetic tracking system.

Recent technical improvements and cost reductions in electromagnetic motion tracking systems invite their application to motion axis determination in the surgical setting. After evaluation of the accuracy of a state-of-the-art D.C. electromagnetic tracking system, which generates complete three-dimensional kinematic outputs from just a single receiver, we calculated screw displacement axes (SDA's) from its source data. The accuracy of SDA determination from such source data was evaluated for various rotational increment sizes around a revolute joint. A novel smoothing procedure, customized for this type of source data, was developed, enabling SDA detection from incremental rotations of less than 1 deg, at an accuracy appropriate for intra-operative measurement of human joint motion. Examples of SDA determination are given for motion tracking of a ball joint and of the elbow articulation.

Electromagnetic Phenomena↗
PubMed1998

Phase I and pharmacokinetic trial of paclitaxel in patients with hepatic dysfunction: Cancer and Leukemia Group B 9264.

PURPOSE: To characterize the maximum-tolerated dose, dose-limiting toxicities (DLTs), and pharmacokinetics of paclitaxel in patients with abnormal liver function. PATIENTS AND METHODS: Adults with tumors appropriate for paclitaxel therapy who had abnormal liver function tests were eligible. Patients were assigned to one of three treatment cohorts: I, AST level twofold normal and bilirubin level less than 1.5 mg/dL; II, bilirubin level 1.6 to 3.0 mg/dL; and III, bilirubin level greater than 3.0 mg/dL. Doses were explored in at least three patients within each cohort. Although designed to assess a 24-hour infusion schedule, the trial was extended to also assess a 3-hour regimen. Pharmacokinetics were to be studied in all patients. RESULTS: Eighty-one patients were assessable for toxicity. Patients with bilirubin levels greater than 1.5 mg/dL had substantial toxicity at all doses explored, whereas the toxicity for patients with elevated AST levels occurred at doses that ranged from 50 to 175 mg/m2 administered over 24 hours. In most patients, the DLT was myelosuppression. The pharmacokinetic data were insufficient to adequately evaluate the relationship between pharmacokinetics and toxicity in patients who received 24-hour infusions but provided evidence of a longer exposure to paclitaxel than anticipated for the doses used in this study in the 3-hour infusion group. CONCLUSION: If paclitaxel is used for patients with elevated levels of AST or bilirubin, dose reductions are necessary, and an increase in toxicity can be anticipated. The increased myelosuppression observed is at least partially because of altered paclitaxel pharmacokinetics in such patients.

Adult↗
PubMed1998

Salvage of a recurrently dislocating total hip prosthesis with use of a constrained acetabular component. A retrospective analysis of fifty-six cases.

Fifty-six constrained acetabular components were placed, between April 1988 and February 1993, in fifty-five patients who had had recurrent dislocations (average, six dislocations; range, two to twenty dislocations) of the femoral component after a previous total hip arthroplasty. All patients had additional factors contributing to the instability of the implant, including absence or disruption of the abductor mechanism, poor health, mental retardation, confusion, and Alzheimer disease. One patient was lost to follow-up. The remaining patients were followed clinically for a minimum of three years (average, sixty-four months; range, thirty-seven to ninety-seven months) or until the time of death. During the follow-up interval, only two (4 per cent) of the fifty-five patients had a subsequent dislocation. The use of this type of component should be considered for patients who have recurrent dislocation if other treatment modalities are unlikely to be effective.

Acetabulum↗
PubMed1998

Temporal and spatial distributions of directional counterface motion at the acetabular bearing surface in total hip arthroplasty.

The motions of counterface articulation against the bearing surface of the acetabular liner strongly influence polyethylene wear debris production in contemporary total hip arthroplasty. However, the available body of relevant articular force and motion information is largely confined to resultant load excursions measured relative to instrumented femoral components, and/or to global angular motions (flexion, adduction, endorotation) of the joint. Analytical frameworks are here developed to transform such information into temporal and spatial variations of the resultant load and of the local counterface sliding velocity relative to an ordered set of discrete locations (e.g., finite element nodes) on the acetabular bearing surface. Whole-duty-cycle time histories of acetabular resultant load and counterface velocity distributions are presented for two important practical situations: human level walking gait, and a 23 degrees biaxial rocking hip simulation machine. The local counterface motions occurring in the simulator are characterized by higher velocities, smoother motion patterns, and wider directional variation than those occurring in human gait.

Acetabulum↗
PubMed1998

The function of posterior tilt of the tibial component following posterior cruciate ligament-retaining total knee arthroplasty.

To increase the range of motion in the knee, posterior cruciate ligament-retaining total knee arthroplasty (TKA), which has a roll back (RB) mechanism, is used. The roll back mechanism is the complex movement of the femoral condyles relative to the tibial plateau, which results in translation of the tibiofemoral contact point posteriorly as the knee is flexed. This study was undertaken to assess the function of the posterior cruciate ligament (PCL) and posterior tibial tilt following PCL-retaining TKA. Eleven fresh-frozen cadaveric normal lower extremity specimens (average age: 75.4 years; range: 69 to 88 years) were obtained for this study. The test was performed on a loading frame after specimen preparation. The calcaneal bone was fixed on the rigid frame. A load of 9.5 kg was applied perpendicularly by the moving frame to femoral head through four casters. PCL strain and RB were measured before and following TKA by changing the posterior tilt of tibial component and the external rotation of femoral component. PCL strain at 105 degrees flexion in the 0 degree posterior tilt group (3.3% +/- 2.4%) was decreased in the 10 degrees posterior tilt group (0.6% +/- 0.5%), and this decrease was statistically significant (p < 0.05). RB was measured as anterior-posterior translation by using an arthroscopic probe. After TKA, RB was decreased in the medial compartment but was increased in the lateral component. These different movements of the tibiofemoral contact points consequently caused rotation in the flexion position. Posterior tilt of the tibial component decreased the efficiency of the PCL's function. Retaining the PCL physically is not the same as preserving the function of the PCL because of the lack of the ACL, the change of the joint line, the differences in articular geometry, and the balance of the ligaments.

Aged↗