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Biomedical subjects

D L Butler

Publications and source records attributed to D L Butler.

At least 37 records · Page 2Linked to original sources

Perspectives on cell and collagen composites for tendon repair.

Cell and matrix composites recently have been used to repair tendons and ligaments. In the current study the authors briefly review prior studies in this area, and the contributions these findings have made toward solving this clinical problem. The authors then provide a perspective on the necessary characteristics that the cells and delivery vehicles of these composites must possess, separately and in combination, to function successfully after surgery. The authors conclude by applying these functional tissue engineering principles to two tendon injury models in which mesenchymal stem cells have been suspended in Type I collagen gel to form composites for patellar and Achilles tendon repair. In the first study, mesenchymal stem cells were suspended in gel (5 million cells/mL) with no attempt to align the cells during incubation. The resulting composites were implanted in window defects in one patellar tendon in the rabbit knee, with gel alone in a matching defect on the contralateral side. Biomechanical evaluation at 4 weeks showed that the material properties of the mesenchy-mal stem cell based repairs were 18% to 33% greater than results for contralateral controls. In the second study, mesenchymal stem cells were suspended in gel (4 million cells/mL), contracted on a tensioned suture during incubation, placed in an Achilles gap defect, and compared with repairs of contralateral gap injuries containing suture alone (controls). By 4 weeks, the repairs treated with mesenchymal stem cells had achieved twice the structural properties of the contralateral controls and 50% to 60% of the stiffness and strength of normal tendons that were not surgically treated. In addition, the material properties of the repairs treated with mesenchymal stem cells had increased with time to 37% of normal by 12 weeks after surgery. Both studies reveal the benefits of using pluripotential cells in a collagen gel matrix, and suggest additional research that might enhance the repair quality of healing tendons.

Animals↗

Escherichia coli ATCC 35218 as a quality control isolate for susceptibility testing of Haemophilus influenzae with haemophilus test medium.

Current National Committee for Clinical Laboratory Standards (NCCLS) susceptibility guidelines for quality control testing with Haemophilus influenzae do not include a beta-lactamase-producing strain that could detect the deterioration of the beta-lactamase inhibitor components of amoxicillin-clavulanic acid, ampicillin-sulbactam, and piperacillin-tazobactam. The objective of the study was to determine if comparable quality control results for Escherichia coli ATCC 35218, a beta-lactamase-producing strain, would be produced for the three beta-lactam-beta-lactamase inhibitor agents with Haemophilus test medium and Mueller-Hinton medium. The criteria used in this study to determine if Haemophilus test medium was acceptable for quality control testing of E. coli ATCC 35218 was that 100% of the results obtained with an antimicrobial agent-methodology combination needed to be within the acceptable NCCLS ranges established with Mueller-Hinton medium. The MIC testing results obtained by the broth microdilution and E-test methods with amoxicillin-clavulanic acid and piperacillin-tazobactam were all within the NCCLS ranges; however, the results obtained with ampicillin-sulbactam by both methods were not within the NCCLS ranges. Acceptable results were obtained by the disk diffusion methodology with ampicillin-sulbactam and piperacillin-tazobactam but not with amoxicillin-clavulanic acid. When performing susceptibility testing with H. influenzae with the beta-lactam-beta-lactamase inhibitors, in addition to quality control testing with H. influenzae ATCC 49247, testing of E. coli ATCC 35218 on Haemophilus test medium is an effective way to monitor the beta-lactamase inhibitors in some antimicrobial agent-methodology combinations.

Culture Media↗

Use of mesenchymal stem cells in a collagen matrix for Achilles tendon repair.

This investigation tested the hypothesis that delivering mesenchymal stem cell-seeded implants to a tendon gap model results in significantly improved repair biomechanics. Cultured, autologous, marrow-derived mesenchymal stem cells were suspended in a collagen gel delivery vehicle; the cell-gel composite was subsequently contracted onto a pretensioned suture. The resulting tissue prosthesis was then implanted into a 1-cm-long gap defect in the rabbit Achilles tendon. Identical procedures were performed on the contralateral tendon, but only the suture material was implanted. The tendon-implant constructs were evaluated 4, 8, and 12 weeks later by biomechanical and histological criteria. Significantly greater load-related structural and material properties were seen at all time intervals in the mesenchymal stem cell-treated tendons than in the contralateral, treated control repairs (p < 0.05), which contained suture alone with natural cell recruitment. The values were typically twice those for the control tissues at each time interval. Load-related material properties for the treated tissues also increased significantly over time (p < 0.05). The treated tissues had a significantly larger cross-sectional area (p < 0.05), and their collagen fibers appeared to be better aligned than those in the matched controls. The results indicate that delivering mesenchymal stem cell-contracted, organized collagen implants to large tendon defects can significantly improve the biomechanics, structure, and probably the function of the tendon after injury.

Achilles Tendon↗

In vivo tendon forces correlate with activity level and remain bounded: evidence in a rabbit flexor tendon model.

While some tendons and ligaments in the lower extremity develop peak forces proportional to the intensity of activity (Komi 1990; Komi et al., 1992; Korvick et al., 1996), others maintain a steady force regardless of activity level (Herzog et al., 1993; Prilutsky et al., 1994). Investigators (Biewener et al., 1988; Korvick et al., 1996) have also shown that peak knee and ankle tendon forces approach one-quarter to one-third of ultimate or failure force values. In the rabbit flexor digitorum profundus (FDP) tendon model we tested several hypotheses, chiefly that peak in vivo forces not only increase with increasing activity but do not exceed one-third of their ultimate or failure values. The FDP tendon was instrumented in three animals, and each rabbit subjected to an experimental design involving three activity levels. Peak tensile forces and rates of rise and fall in tendon force increased significantly with increasing activity (p < 0.01). Further, the tendon maintained a non-zero force level throughout all trials. For the most vigorous activity, inclined hopping, tensile forces and stresses were, on average, within 30% of the tendon's ultimate force and stress values, respectively. Such in vivo measurements in different tendon systems should help investigators better understand the recruitment and contribution of important muscle-tendon units to joint stability and gait.

Animals↗

Effect of tibial attachment location on the healing of the anterior cruciate ligament freeze model.

We studied the healing response of a devitalized anterior cruciate ligament to a treatment of initial anterior-posterior joint translation in goats. Devitalization and devascularization were achieved by five successive freeze-thaw cycles. Anterior-posterior translation was surgically altered by an osteotomy of the tibial attachment of the devitalized ligament and its reattachment either in the anatomical position or in a position 5 mm posterior. Six weeks after the first surgery, the same procedure was performed on the contralateral limb, except that the ligament was reattached in the alternate position. Six months after the initial surgery, femur-anterior cruciate ligament-tibia specimens were tested to determine their structural and mechanical material properties. Anatomic ligament placement resulted in reduced anterior-posterior translation (p < 0.05) and greater anterior joint stiffness (p < 0.05). Maximum load (p < 0.05) and ligament stiffness (p < 0.01) also were greater for the anatomically placed anterior cruciate ligaments. The maximum load for anatomically placed ligaments averaged 1.625 +/- 211 N (SEM). The strength of the posteriorly placed anterior cruciate ligament, 895 +/- 164 N was similar to results of historical anterior cruciate autograft reconstructions. Ligament failure occurred near the tibial insertion in the posteriorly placed ligaments more often than in the anatomically placed ligaments (four of five times compared with one of five times). Ligament failure near the tibial insertion occurred with lower mean maximum load than failure at the midsubstance or by bone avulsion (796 compared with 1.592 N: p < 0.05). These data support the hypothesis that ligament laxity is important to the healing and remodeling of anterior cruciate ligament grafts.

Animals↗

The use of an implantable force transducer to measure patellar tendon forces in goats.

Patellar tendon (PT) force was measured during activity with an implantable force transducer (IFT) in adult goats. PT force, vertical ground reaction force (VGRF) and the animal's speed were recorded for standing, walking and trotting. Following data collection, animals were euthanized and the IFT calibrated in vitro. Standing PT force averaged 207 N. Maximum PT force was approximately 800 N for walking and 1000 N for trotting and occurred at mid-stance. PT force dropped from 200 N at toe-off to 0 N by mid-swing. For each activity, the PT force increased with increases in VGRF. Maximum in vivo PT stress occurred during trotting and measured 29 MPa. This study demonstrates the IFT's usefulness in measuring tendon force directly.

Animals↗

Teaching low achievers and students with learning disabilities to plan, write, and revise opinion essays.

A total of 38 problem learners comprising adolescents with learning disabilities and low achievers participated in this study. Of these, 20 were untrained control participants; the remainder were trained to plan, write, and revise opinion essays. Trainees were randomly divided into pairs and taught to collaboratively use interactive dialogues to plan and revise their essays (but they wrote their essays separately). The results from multivariate analyses of variance (MANOVAs) and effect sizes indicated that trainees improved significantly from pretest to posttest in clarity and cogency of written opinion essays, and maintained such gains. Additional analyses indicated that they surpassed the untrained control group. Questionnaire data indicated trainees improved in self-efficacy of writing only. The same finding held true in comparison with untrained participants. The discussion integrates the trainees' performance data with the questionnaire data and considers the research implications and limitations of the study.

Achievement↗

Dose-dependent response of gamma irradiation on mechanical properties and related biochemical composition of goat bone-patellar tendon-bone allografts.

We studied the effects of gamma irradiation on the dimensions, mechanical and material properties, and mature hydroxypyridinium crosslink density of collagen in goat patellar tendon-bone specimens. Left and right patellar tendon-bone units were removed from 10 adult female goats and were bisected longitudinally. Each tendon half was frozen, and then the left halves were exposed to 4, 6, or 8 Mrad (40,000, 60,000, or 80,000 Gy) of gamma irradiation. The contralateral tendon halves served as controls (no irradiation). Each specimen then was loaded to failure in tension, and its soft-tissue midsubstance was processed to measure collagen content and hydroxypyridinium crosslink density. Dose-dependent reductions in the mechanical properties were found, including 46% (p < 0.01) and 18% (p < 0.05) reductions in maximum force and stiffness, respectively, at 4 Mrad. Similar reductions were noted in material properties, including 37% (p < 0.005) and 8% (p > 0.05) reductions in maximum stress and modulus, respectively, at 4 Mrad. These results are consistent with our previous report involving 2 and 3 Mrad (20,000 and 30,000 Gy) of exposure. We also found significant decreases in hydroxypyridinium crosslink density with 6 Mrad of irradiation (p < 0.05). However, since only one biomechanical parameter (modulus) correlated significantly with only one biochemical measure (hydroxypyridinium crosslink density) (p < 0.05), other possible mechanisms also are being explored to more fully explain these dose-dependent changes.

Analysis of Variance↗

In vivo quantification of the cat patellofemoral joint contact stresses and areas.

A new method for in vivo measurement of patellofemoral joint contact areas, stresses, and patellar displacements, with joint loading approximating physiologic conditions was developed. Joint contact measurements were obtained using pressure sensitive film inserted directly between articular joint surfaces. Two-dimensional joint kinematics were measured using a high-speed video based motion analysis system. Joint loading, provided by quadriceps muscle stimulation, was measured with an implantable force transducer (IFT). Variations in joint mechanics as a function of joint flexion angle, joint loading and joint stability (anterior cruciate ligament intact or transected) were determined for four adult male cats. The contact measurements obtained with the pressure sensitive film displayed high repeatability with a standard error of +/- 6.8% of the mean value of the median pressure and +/- 4.4% of the mean contact area value. Substantial differences in joint mechanics were reliably detected with the new technique. The influence of experimental procedures, such as incisions in the joint capsule and insertion of pressure sensitive film between the articular surfaces, produced minimal changes in the joint kinematics during muscular contraction.

Animals↗

Promoting strategic learning by postsecondary students with learning disabilities.

The research described here investigated the effectiveness of an intervention model designed to promote self-regulated and strategic learning: Strategic Content Learning (SCL). In SCL, rather that focusing on teaching students specific cognitive strategies, instruction focuses on supporting students to develop a strategic approach to learning. The study comprised six parallel case studies embedded within a single-group, pre-post design. Each student chose a task of importance to current or future academic work, and individualized support was provided on those tasks. Participants were adults with learning disabilities (5 women and 1 man, ages 18 to 36 years) enrolled in postsecondary education programs. Results indicated, that students' task performance improved. Additionally, gains in metacognitive knowledge about tasks and strategies, increased perceptions of self-efficacy, and shifts in attributional patterns were observed. Most critically, the evidence suggested that students became more self-regulated in their learning: They were active in developing and modifying strategies, they transferred strategies across contexts, and they began to attack noninstructed tasks strategically. The particular suitability of SCL as an intervention for adults with learning disabilities is described, and implications of the findings for research and practice are discussed.

Adolescent↗

In vivo forces in the anterior cruciate ligament: direct measurements during walking and trotting in a quadruped.

In vivo forces in the anterior cruciate ligament (ACL) were measured in three adult goats during quiet standing and during gait (walking or trotting). A modified pressure transducer (MPT) was implanted within the anteromedial band of the ligament to make direct measurements of ACL force. One or two days following implantation, measurements were made of ACL force, knee joint flexion angle, ground reaction forces, and speed of locomotion. MPT calibration was performed in vitro using anteroposterior displacement tests at six flexion angles. The ACL was loaded during quiet standing (30-61 N) and during the stance phase of gait. Peak ACL forces were achieved within the first 40% of stance, with magnitudes ranging from 63 to 124 N during walking and from 102 to 150 N during trotting. The average ACL force during the stance phase ranged from 34 to 68 N while walking and from 46 to 69 N while trotting. The partial correlations between peak ACL force and speed, and between average ACL force and speed, were both statistically different from zero (p < 0.01). ACL forces dropped to zero during the swing phase in all trials. ACL forces were less than 15 N throughout swing in two of the animals, both of which did not extend their knees during gait beyond 20 degrees from full extension. In the animal which did show knee extension beyond 40 degrees (20 degrees from full extension), ACL loading occurred during late swing. The magnitude of the peak ACL force during late swing was significantly correlated with the extent of knee extension in this animal.

Animals↗

The effects of 4 Mrad of gamma irradiation on the initial mechanical properties of bone-patellar tendon-bone grafts.

Pairs of frozen human patellar tendon-bone (PTB) ligament allografts were exposed to either 0 or 4 Mrad of gamma irradiation sterilization, the latter value based on recent reports suggesting higher dosage levels for adequate sterilization against the human immunodeficiency virus. All specimens were subjected to three levels of loading: lower functional loads, higher functional loads, and failure. Lower functional loads were simulated by performing in vitro static and cyclic creep tests, similar to loads that the surgeon and patient would apply before and after implantation, respectively. Higher functional loads, simulating moderate activities of daily living, were represented by the slope of the linear portion of the force-elongation curve or linear stiffness. Failure or trauma was then simulated by failing the grafts in tension at a high strain rate. We found that the irradiation treatment shortened the tendon by only 0.6 mm, which was nevertheless statistically significant (p < 0.01). By contrast, 4 Mrad did not significantly alter either static or cyclic creep (p > 0.05) at lower functional loads. Instead, irradiation produced the greatest changes during failure testing, reducing both the graft's linear stiffness by 12% (p < 0.025) and maximum force by 26% (p < 0.001). Although our data do not describe how an allograft might perform during the early healing and later collagen-remodelling phases, such in vitro studies remain important if we are to optimize allograft properties before arthroscopic anterior and posterior cruciate ligament reconstruction.

Adult↗

A technique for the evaluation of the contributions of knee structures to knee mechanics in the knee that has a reconstructed anterior cruciate ligament.

A technique to quantify the restraining action of specific knee structures during anterior/posterior (A/P) tibial displacement tests in the goat knee that has a reconstructed anterior cruciate ligament (ACL) is described. Joint specimens were mounted in an instrumented test stand to measure both the forces on, and resulting translations of, the tibia in the A/P direction. The intact grafted knee was tested first, after which structures were sequentially cut or removed, or both, and the test was repeated. The ACL graft remained intact in the joint during this process; therefore, subsequent axial failure testing was possible. Analysis of the resulting force-displacement curves allowed the percentage contribution and anterior joint stiffness to be determined for each structure at a fixed anterior displacement in 12 goat knees 6 months after ACL allografting. The allografts were found to provide about 56% of the total restraining force, more than any other structure examined. Studies of this kind will be important in the documentation of the changing role of an autograft or allograft in a reconstructed knee over time.

Animals↗

Stabilization of thymopentin and preservation of its pharmacological properties by 2-hydroxypropyl-beta-cyclodextrin.

Thymopentin prepared in 5, 15, and 20% 2-hydroxypropyl-beta-cyclodextrin (HPCD) was able to inhibit guinea-pig ileum contraction stimulated by anatoxin-a (3 x 10(-6) M) after fourteen months of storage at room temperature. Thus, in contrast to the instability of thymopentin prepared without HPCD, the pharmacological activity was retained and could be stored in a ready-to-use solution for extended periods without refrigeration.

2-Hydroxypropyl-beta-cyclodextrin↗

In vitro evaluation of an implantable force transducer (IFT) in a patellar tendon model.

A new implantable transducer has been developed for in situ evaluation of ligament and tendon forces. Unlike previous devices, this sensor is placed within the specimen, minimizing measurement errors due to impingement on surrounding soft tissues and bone. In this study, we present the sensor design details as well as test results from initial in vitro trials in the goat patellar tendon model. Device performance and influence of the device on the specimen were evaluated under several loading conditions. In all cases, device output had a strong correlation with induced tissue load. Significant variations in device performance were only noted at high tissue deformation rates. More extensive investigations will be conducted to assess how changes in transducer design might alter performance characteristics.

Animals↗

The use of wide area computer networks in disaster management and the implications for hospital/medical networks.

Computer-mediated communication in various forms is already being used in all phases of disaster management--preparation, response, recovery, and long-term mitigation. However, to date wide area computer networks--particularly the Internet (the supernetwork of networks)--have been used only to a limited extent in disaster management and prevention. Some of these applications are described in this paper. Nevertheless, the high speed and ease of information transfer by computer network and the vast resources becoming available on the Internet make it inevitable that the use of computer networks to temper disasters will increase enormously in the next decade. The Internet will provide a key means through which networks initially dedicated to solely medical purposes and the individuals who use them will become involved not only in disaster response and mitigation worldwide, but in the global community and consciousness that is the Internet.

Australia↗