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Biomedical subjects

T D Brown

Publications and source records attributed to T D Brown.

At least 181 records · Page 10Linked to original sources
PubMed1990

Laboratory evaluation of prophylactic knee brace performance under dynamic valgus loading using a surrogate leg model.

Because of contradictory data accumulating from on-field trials of prophylactic knee braces, benchtop laboratory studies of brace performance have become important. This study (1) describes design considerations for a mechanical leg surrogate developed for prophylactic brace testing, (2) validates surrogate performance under dynamic lateral loading, and (3) reports comparative performance data for eight commercial knee braces tested using this surrogate system.

Braces↗
PubMed1990

Mechanical analysis of the factors affecting dynamization of the Orthofix Dynamic Axial Fixator.

Loading trials were conducted to identify mechanical factors affecting dynamization of a commercially available external fixator (Orthofix) that is designed to undergo free telescopic motion when axially loaded. Angular variations between the proximal and distal screw clamps and the telescoping fixator body failed to produce fixator binding (failure to dynamize) in any of the loading trials. However, binding was produced by applying external torques in magnitudes that occasionally occur during routine ambulation. The specific torque necessary to induce binding (typically 3-4 Nm) was only a weak function of axial load magnitude, axial loading frequency, or simulated fracture stiffness. Among several geometrical variables of fixator application, only the pre-extension of the telescoping body and circumferential misalignment between proximal and distal pin clusters had an appreciable influence on the threshold binding torque. Axial fixator motions were also monitored in a small adjunct clinical series of 22 dynamized tibial fractures. The fixator dynamized appropriately in 15 cases (68%). Three patients (14%) showed evidence of fixator binding, and another four (18%) had less than predicted slider excursions. The role of several design factors implicated in torque-induced fixator binding is discussed in light of the benchtop and clinical observations.

Biomechanical Phenomena↗
PubMed1989

Phase I clinical and pharmacokinetic trial of Brequinar sodium (DuP 785; NSC 368390).

Brequinar sodium is a 4-quinolinecarboxylic acid analogue that inhibits dihydroorotate dehydrogenase and subsequent de novo pyrimidine biosynthesis. It has shown dose-dependent antineoplastic activity against several mouse and human tumor models. This trial evaluated Brequinar given as a single daily i.v. bolus over a 5-day period repeated every 28 days. One hundred seven courses of treatment at dosages ranging from 36 to 300 mg/m2/day x 5 were administered to 45 patients (31 male and 14 female) with refractory solid tumors; median age was 58 years (range 30-74); median Southwest Oncology Group performance status was 1 (range, 0-3). Thirty patients had prior cytotoxic chemotherapy. Dose-limiting toxicities were thrombocytopenia and a severe desquamative maculopapular dermatitis. Two of 5 good risk patients at 300 mg/m2 and 3 of 6 poor risk patients at 170 mg/m2 developed a platelet count less than 25 x 10(3)/microliters. Two of 5 good risk patients at 300 mg/m2 and 1 of 6 poor risk patients at 170 mg/m2 developed a severe desquamative dermatitis. Moderate to severe mucositis was usually associated with the thrombocytopenia and/or the dermatitis. Nonhematological drug-related toxicities included nausea and vomiting, malaise, anorexia, diarrhea, phlebitis, reversible transaminase elevation, and mucositis. Other hematological toxicities were anemia, granulocytopenia, and leukopenia. There were no drug-related deaths. There were no objective tumor responses. Plasma and urine levels of Brequinar were quantified by high pressure liquid chromatography in 28 patients. Plasma levels and areas under the curve increased proportionally with increased dose. Brequinar had a harmonic mean terminal t1/2 of 8.1 +/- 3.6 h with a model-independent determined apparent volume of distribution at steady state of 9.0 +/- 2.9 liters/m2 and a total body clearance of 19.2 +/- 7.7 ml/min/m2. Renal excretion was a minor route of elimination for Brequinar. The maximally tolerated dose of Brequinar on a daily x 5 i.v. schedule was 250 mg/m2 for good risk patients. For the daily x 5 i.v. schedule, the recommended dose of Brequinar for phase II evaluation is 250 mg/m2 for good risk patients and 135 mg/m2 for poor risk patients.

Adult↗
PubMed1989

A microvascular anastomotic device: part I. A hemodynamic evaluation in rabbit femoral arteries and veins.

This study quantitatively assesses the hemodynamic consequences of inserting a 1.5-mm polyethylene anastomotic device in both small arteries and veins. The device was placed in 20 rabbit femoral arteries and 20 femoral veins. Using 20-MHz pulsed ultrasonic Doppler velocimetry techniques, blood flow was measured in 5 immediate postoperative intervals and at the 24-hour and 3-week postoperative intervals. In arteries, volumetric flow (Q) was not statistically different in any postoperative interval; maximum spatial velocity (Vmax) was significantly increased in the immediate postoperative intervals but was not different at 24 hours or 3 weeks. In veins, significant decreases in Q and increases in Vmax occurred in the immediate postoperative intervals, but differences were not noted at the 24-hour or 3-week intervals. The results of this study indicate that the hemodynamic consequences of anastomosing small vessels with a polyethylene device are minimal and that this mechanical technique is an effective method for experimental microvascular repairs.

Anastomosis, Surgical↗
PubMed1989

Cardiovascular rhythm effects of gamma recombinant DNA interferon.

Twenty patients receiving recombinant DNA gamma interferon were prospectively assessed for cardiac rhythm disturbances. All patients were evaluated with baseline electrocardiograms, pretreatment ambulatory monitoring and ejection fraction determination. Each patient was then monitored continuously during drug administration. Quantitative ventricular ectopy was not increased, nor were average heart rate, maximal heart rate, or quantitative supraventricular ectopy when comparing baseline to during therapy parameters. Complex cardiac ectopy and noteworthy cardiac events (NCE) were defined and identified in 2/20 (10%) patients pretreatment, and in 8/18 patients (44%) with normal baseline tracings during treatment (p = .02). This difference was not apparent when corrected for total days monitored pre- and post treatment (p greater than .2). These consisted predominantly of nonsustained short duration ventricular tachycardia (seven of eight patients). We conclude that life threatening cardiac events are uncommon with gamma interferon therapy.

Adult↗
PubMed1989

The effects of grip proximity on perceived local in vitro tendon strain.

In vitro tensile loadings were performed on a series of sequentially-shortened canine tendon specimens which had been instrumented with mercury strain gages. The purpose of the experiments was to determine the tendon length necessary to ensure that the perceived local strain was effectively independent of the gripping configuration. The results showed that the mercury strain gage outputs exhibited statistically significant departures from initial (long tendon) values only when the tendons were shortened to lengths of less than about eight diameter multiples.

Animals↗
PubMed1989

A finite-element analysis of the effects of intertrochanteric osteotomy on stresses in femoral head osteonecrosis.

The efficacy of osteotomy for the precollapse stage of femoral head necrosis depends on altering load transmission. The alteration must reduce the stress levels on the infarcted bone during the process of repair. The prospects for success in this regard would likely be improved by the ability to predict reliably the stress changes derived from specific osteotomies for specific femoral head involvement patterns. For this reason, an anatomic three-dimensional finite-element model has been designed to compute necrotic femoral head stress changes that accompany varus, valgus, and rotational osteotomies. Four specific patterns of femoral head infarction are considered. Comparison of the patterns of load transmission at ten discrete instants (spanning the stance phase of the gait cycle) revealed that the critical stresses in the most commonly infarcted anterolateral and central femoral head regions occur just after the instant of heel-strike. For the femoral head with a deep, narrow lesion in the weight-bearing tract, and for classic wedge-shaped segmental infarct, the data showed that 30 degrees varus osteotomy was beneficial in reducing stress levels through much of the infarcted region. The 30 degrees valgus osteotomy was less successful. Neither 30 degrees anteversion nor 30 degrees retroversion osteotomies caused substantial changes in stresses for infarcted regions along the weight-bearing tract. For the case of a wide, shallow lesion or for whole femoral head involvement, none of the four osteotomies considered was able to achieve appreciable net reduction of stresses in weakened, infarcted regions.

Adult↗
PubMed1988

Pulsed ultrasound Doppler velocimetry in the assessment of microvascular hemodynamics.

Pulsed ultrasonic Doppler velocimetry (20 MHz) (PUDVM) has evolved considerably in the last 10 years. Engineering development has resulted in a computer-controlled vessel-scanning instrument whose backscattered frequency shift spectra are analyzed using fast Fourier transforms (FFT). Benchtop and theoretic studies indicate accurate (error less than 5%) velocity and volumetric flow rate measurements in vessels with a lumen diameter as small as 1.2 mm. Clinical application of the PUDVM has provided transcutaneous measurements of blood flow variables in normal human digital arteries. Experimental application to arteries 1.0-1.5 mm has provided information on the hemodynamic effects of topical vasodilators, standard microarteriorrhaphy, variations in microvascular technique, interpositional grafts, and early wound repair. With improving computer capabilities and technical modifications, the PUDVM will be an increasingly important tool in clinical and experimental microsurgery.

Blood Flow Velocity↗
PubMed1988

Contact stress aberrations following imprecise reduction of simple tibial plateau fractures.

Despite the well-recognized association between poorly reduced intraarticular fractures and late degenerative changes, current guidelines regarding the reduction precision necessary to avoid excessive cartilage pressures are based largely on anecdotal clinical observations. To gain a quantitative appreciation of the relation between local pressure elevations and fracture reduction imprecision, a simplified laboratory cadaver model of minimally displaced tibial plateau fractures was developed. Cartilage contact stress distributions were measured as a function of depressed fragment malreduction in seven knees, using high-resolution (100 pixels/mm2) digital image scans of Fuji-film stain patterns. The contact stress data showed a general trend of increases of peak local pressure with increasing fracture site incongruity, and in a few isolated instances the effect was very pronounced. Across the whole series, however, statistically significant departures from anatomic pressure levels did not occur until the fragment stepoff was greater than 1.5 mm. Even at the 3-mm stepoff level, for which the depressed fragment usually no longer made contact with the femoral condyle, the peak local pressure values on the intact side of the fracture line averaged only approximately 75% greater than those prevailing anatomically. Given the successful clinical outcomes normally achieved for conservatively managed simple tibial plateau fractures having stepoff magnitudes (5-10 mm) clearly sufficient to insure fragment articular noncontact, the present laboratory results suggest that nominally factor-of-two peak local pressure elevations, provided that they occur over only small portions of the cartilage surface, are probably within the long-term overall tolerance range of an articular joint.

Aged↗
PubMed1988

Global mechanical consequences of reduced cement/bone coupling rigidity in proximal femoral arthroplasty: a three-dimensional finite element analysis.

Component loosening in total hip arthroplasty is often accompanied by substantial bony remodelling, associated initially with reduced stiffness of the cancellous bone bordering the cement, and eventually with the formation and proliferation of a compliant fibrous membrane at the bone/cement interface. An anatomically based three-dimensional finite element model has been developed to explore the salient stress changes occurring with progressive degradation of the stiffness of the cancellous bone in a thin zone bordering the cement. This border zone, modelled as a distinct linearly elastic and isotropic material layer, assumed a geometry and a range of mechanical properties inferred from eventual membrane thickness apparent in recent animal studies of component loosening. The major variables considered were: stiffness (elastic modulus) and compressibility (Poisson ratio) of the border zone, stiffness changes in the outlying cancellous bone, resultant hip contact force, and trochanteric muscle loadings. The results for the limiting case of a non-degraded border zone compared reasonably with previous studies of femoral reconstructions having rigid bone-to-cement attachment. Progressive decay of border zone stiffness produced complex changes in load transmission. Foremost among these were a generalized increase in stress levels (especially of transverse-plane tension) in the proximo-lateral cancellous bone, and a corresponding generalized decrease in stress levels in the proximo-medial cancellous bone. There were also large bending moment increases in the prosthesis and its cement mantle, especially at mid-stem. At almost all sites, the critical stress levels were those developed for peak stance-phase loading, rather than for the lower loads (and different resultant contact force directions) occurring elsewhere in the gait cycle. The elevated proximo-lateral cancellous bone stresses occurring with eventual membrane development, consistent with localized bony hypertrophy seen in recent animal studies, may be a response to hoop stresses occurring during pistoning of the tapered cement mantle.

Bone Cements↗
PubMed1988

Comparative study of the Orthofix and Pittsburgh frames for external fixation of unstable pelvic ring fractures.

We compared the mechanical performance of the Orthofix pelvic external fixator with that of the Pittsburgh triangular frame (PTF) on eight fresh-frozen cadaver pelves with experimentally created Malgaigne (double-vertical) fracture/dislocations. The pelves were quasi-statically loaded in longitudinal compression and loss of reduction (i.e., failure) was defined as 1.5 cm of diastasis at either of the fracture/dislocation sites. The Orthofix frame-pelvis complex (four 6-mm half-pins) was comparable to the PTF-pelvis complex (eight 5-mm half-pins) in terms of load to failure and overall stiffness, but was 4-7 times stiffer at lower load levels. Both frame-and-pin complexes deformed moderately at the pin-bone interface, but, while the PTF also showed moderate displacement between frame components, the Orthofix had almost no frame intercomponent motion.

Adult↗
PubMed1988

Effects of episodic air hammer usage on digital artery hemodynamics of foundry workers with vibration white finger disease.

Blood flow was measured in the proper radial digital arteries of 20 subjects, 11 of whom were experienced pneumatic chipping hammer operators with varying degrees of vibration white finger (VWF). Flow was measured noninvasively and transcutaneously using a 20-MHz pulsed ultrasonic Doppler velocimeter (PUDVM), both in the resting state and after performing a supervised 20-minute chipping sequence. Approximately equivalent pre-chipping flow rates were present in six chippers with severe VWF, in the remaining five chippers without severe VWF, and in nine age-matched chipping novices. However, the digital artery flow rates of the severe VWF group increased substantially (to about three times the resting level) after the chipping episode, whereas the flow rates of the novices and the non-VWF chippers did not change appreciably. The VWF blood flow increases were accompanied by an 11% heart rate increase, by a 60% increase in lumen cross-sectional area at the PUDVM scan site, and by a very substantial reduction in downstream resistance (a 90% increase in temporospatial mean velocity).

Blood Flow Velocity↗
PubMed1988

Effect of osteochondral defects on articular cartilage. Contact pressures studied in dog knees.

Full thickness osteochondral defects 6 mm in diameter were created in the weight-bearing regions of the femoral condyles in 5 adult mongrel dogs to study the contact pressure changes accompanying healing. A digital imaging technique employing Fuji Prescale film mapped contact pressures following 11 months of healing for comparison with contralateral normal knees, and knees with freshly made defects. Although all defects healed uneventfully with subchondral plate reconstitution and with growth restoration of the articular surface, the repair soft tissue appeared histologically to be primarily fibrous tissue, with varying degrees of a fibrocartilaginous component. The mean and peak stresses about fresh defects were not appreciably different from those about healed defects. Neither were there substantial differences in the total cartilage area making contact, except when very low loads were applied. The results suggest that the repair tissue is of poor mechanical quality, and does not contribute appreciably to weight bearing. The cartilage adjacent to the defect did not experience high stresses; neither gross nor light microscopic evidence of degeneration appeared at 11 months. If degeneration does occur following such defects, our data suggest that it is not because of elevated contact stresses.

Animals↗
PubMed1987

An efficient ribosomal frame-shifting signal in the polymerase-encoding region of the coronavirus IBV.

The polymerase-encoding region of the genomic RNA of the coronavirus infectious bronchitis virus (IBV) contains two very large, briefly overlapping open reading frames (ORF), F1 and F2, and it has been suggested on the basis of sequence analysis that expression of the downstream ORF, F2, might be mediated through ribosomal frame-shifting. To examine this possibility a cDNA fragment containing the F1/F2 overlap region was cloned within a marker gene and placed under the control of the bacteriophage SP6 promoter in a recombinant plasmid. Messenger RNA transcribed from this plasmid, when translated in cell-free systems, specified the synthesis of polypeptides whose size was entirely consistent with the products predicted by an efficient ribosomal frame-shifting event within the overlap region. The nature of the products was confirmed by their reactivity with antisera raised against defined portions of the flanking marker gene. This is the first non-retroviral example of ribosomal frame-shifting in higher eukaryotes.

Amino Acid Sequence↗