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Biomedical subjects

David C Markel

Publications and source records attributed to David C Markel.

14 recordsLinked to original sources

Success of clinical pathways for total joint arthroplasty in a community hospital.

Clinical pathways for total joint arthroplasty have been implemented successfully during the past decade. We report the results of pathway use for primary elective total hip and total knee arthroplasty in a community teaching hospital. We evaluated pathway efficacy using patient data forms and the hospital's financial database. Before instituting the pathway, the average length of stay was 4.41 days for patients having total hip arthroplasty and 3.92 days for patients having total knee arthroplasty. The average length of stay for patients having total hip arthroplasty decreased to 3.24 days and to 2.98 days for patients having total knee arthroplasty. Press Ganey Survey results showed high patient satisfaction rates before and after pathway initiation. Pathway implementation did not lead to increased complication rates or readmissions. Despite higher expected increases in the overall healthcare cost during the time of implementation (3 years), direct cost increases were limited to 3.48%. The key elements contributing to pathway success included preoperative patient education, standardized orders derived from evidence-based medicine, and a nurse practitioner who championed the pathway and ensured compliance. We recommend clinical pathways for patients having total joint arthroplasties to reduce length of stay, facilitate effective resource use, and preserve quality of care without compromising patient satisfaction or safety.

Aged↗

Inflammatory and immunological responses to hyaluronan preparations. Study of a murine biocompatibility model.

BACKGROUND: Intra-articular injection of hyaluronan preparations is a popular treatment for osteoarthritis of the knee. Recently, clinical reports have described acute inflammatory reactions in joints following these injections. The purpose of this study was to use a murine pouch model to study the local inflammatory and possibly immunological effects of three commercially available hyaluronan-derived products. METHODS: Each of three different hyaluronan products (Synvisc, Hyalgan, and Supartz) was injected into air pouches established in groups of BALB/c mice. A positive control group (with particle-induced inflammation) and a negative control group (injected with saline solution) were also included. After fourteen days, the mice were killed and the air pouches were explanted and prepared for histological evaluation of the local inflammatory reaction. The antibody response was measured with use of ELISA (enzyme-linked immunosorbent assay) of serum samples obtained after the mice were killed. RESULTS: Histological analysis revealed a significant increase in total membrane cellularity (p < 0.001 to p < 0.03) after the use of all hyaluronan preparations. The increased cellularity was attributed to an inflammatory cell influx, rather than accumulation of fibroblasts, and elevated lymphocyte counts were observed in membranes stimulated by Synvisc (hylan G-F 20). The ELISA data revealed an antibody response to the Synvisc preparation. This immunological response was directed against a non-hyaluronan portion of the product, as indicated by the lack of cross-reactivity with the other hyaluronan products. CONCLUSIONS: These findings demonstrate that all three hyaluronan preparations, as currently manufactured, can cause an inflammatory soft-tissue reaction, but only the non-hyaluronan portion of the Synvisc product created an immunological response. It appears likely that this component may be the target of adverse responses in patients.

Adjuvants, Immunologic↗

Blockade of vascular endothelial growth factor activity suppresses wear debris-induced inflammatory osteolysis.

OBJECTIVE: Aseptic loosening is a common complication of total joint replacement in humans. Our study examined the hypothesis that wear debris may influence vascular endothelial grow factor (VEGF) expression, and that blocking VEGF bioactivity might improve wear debris-induced inflammatory osteolysis in a mouse model. METHODS: Ultra high molecular weight polyethylene (UHMWPE) particles were introduced into established air pouches on BALB/c mice, followed by implantation of calvaria bone from syngeneic littermates. Mice were treated with recombinant VEGF, or VEGF inhibitor (VEGF R2/Fc chimera) or vehicle control, and mice without UHMWPE stimulation were also included. Pouch tissues were harvested 2 weeks after bone implantation for molecular and histological analyses. RESULTS: Exposure of UHMWPE particles increased VEGF expression at both mRNA and protein levels in pouch tissues. Immunostaining revealed intense VEGF staining predominantly in UHMWPE deposit foci surrounded by inflammatory cells. VEGF inhibitor treatment strongly attenuated tissue inflammation (cellular infiltration, membrane proliferation, and expression of interleukin 1beta and tumor necrosis factor-alpha in UHMWPE-stimulated pouch tissues). Further, VEGF inhibitor treatment caused a significant reduction in the number of TRAP+ cells, and effectively prevented UHMWPE particle-induced bone resorption of implanted calvaria (assessed by extent of collagen depletion and frequency of bone erosions). CONCLUSION: The observation that VEGF inhibitor treatment prevented UHMWPE particle-induced inflammatory osteolysis opens new possibilities for treatment of aseptic loosening, especially at an early stage.

Animals↗

Association between UHMWPE particle-induced inflammatory osteoclastogenesis and expression of RANKL, VEGF, and Flt-1 in vivo.

Wear debris-induced vascularized granulomatous periprosthetic tissue may augment the progress of prosthetic loosening, a major clinical problem after total joint replacement. The purpose of this study is to investigate the association of ultra-high-molecular-weight polyethylene (UHMWPE) particle-induced inflammatory osteoclastogenesis and expression of RANK/RANKL and VEGF/VEGF receptors (Flt-1 and Flk-1) using a mouse osteolysis model. UHMWPE particles were introduced into established air pouches on BALB/c mice, followed by implantation of calvaria bone from syngeneic littermates. Mice were injected with either recombinant VEGF or VEGF inhibitor (VEGF R2/F(c) Chimera). Mice without drug treatment, as well as mice injected with saline alone were included. Each group contains 10 mice. Pouch tissues were harvested 2 weeks after bone implantation for histological and molecular analysis. UHMWPE stimulation significantly increased VEGF gene expression, and exerted a lower enhancement effect on the gene expression of Flt-1 and Flk-1. UHMWPE-stimulated VEGF production was markedly reduced by VEGF inhibitor treatment. Immunofluorescent staining indicated that pouch tissue macrophages were the main source of both VEGF and Flt-1 production. A positive association was observed between tissue inflammation and the levels of VEGF and Flt-1 gene transcripts. Both RANK and RANKL gene transcripts were significantly increased by UHMWPE stimulation, which was subsequently reduced by VEGF inhibitor treatment (p<0.05). VEGF treatment increased TRAP(+) cells in pouches either with or without UHMWPE particle stimulation, and VEGF inhibitor treatment caused a significant reduction in the number of TRAP(+) cells in UHMWPE-containing pouches. This study suggests that VEGF has a role in the regulation of RANK/RANKL-mediated osteoclastogenesis, and warrant future investigations to elucidate the role of VEGF signaling in the pathogenesis of prosthetic loosening.

Animals↗

The effect of posterior tibial slope on range of motion after total knee arthroplasty.

Posterior slope has been theorized as advantageous to range of motion (ROM) after total knee arthroplasty. This study was undertaken to assess the accuracy of a 0 degrees and a 5 degrees posterior sloped intramedullary (IM) cutting guide and the effect of the posterior tibial slope on postoperative ROM. Thirty-one consecutive patients underwent total knee arthroplasty using a cutting block and intramedullary cutting guide designed to impart a 0 degrees posterior tibial slope (group 1). A 5 degrees tibia cutting block was used in 30 subsequent patients (group 2). The posterior slope measurement represented the angle between a line drawn parallel to the articular surface and a line drawn perpendicular to the long axis of the tibia on a lateral radiograph. Mean postoperative tibial slope measured 1.8 degrees for group 1 and 5.5 degrees for group 2. There was no significant difference between groups for postoperative flexion or improvement of Hospital for Special Surgery score. The tibial cutting guides accurately achieved the intended posterior slope, but increasing posterior slope did not result in a significant increase in ROM or Hospital for Special Surgery functional score.

Arthroplasty, Replacement, Knee↗

Computer assisted navigation in total knee arthroplasty: comparison with conventional methods.

The success of knee arthroplasty is dependent on many factors. Postoperative extremity and component alignment are important determinants of outcome and longevity. Malalignment (>3 degrees ) results in higher failure rates. Computer-assisted navigation devices were developed to improve implant positioning. This study evaluated the early outcomes of a high-volume fellowship-trained surgeon relative to component positioning and limb alignment using an image-free navigation system. The navigation group consisted of 116 consecutive patients, and the conventional group consisted of 51 consecutive patients. The postoperative mechanical axis was within 3 degrees of neutral mechanical alignment in 95% of the navigation cases vs 84% of the conventional cases (P < .02). The range of the alignment and component position measurements narrowed, and the undesired outliers decreased. Accuracy was improved with navigation. Navigation was a viable device to improve the outcome of total knee arthroplasty relative to limb and component alignment.

Adult↗

Unicompartmental knee arthroplasty: troubleshooting implant positioning and technical failures.

Improvements to implant design and the advent of minimally invasive surgery have increased the popularity of unicompartmental knee arthroplasty. Minimally invasive techniques for implant placement can augment the unicompartmental knee arthroplasty procedure and allow for more rapid rehabilitation and return to activities of daily living. Nevertheless, new technologies are accompanied by learning curves and rediscovery of past mistakes. Unicompartmental knee arthroplasty tends to be more technically demanding than total knee arthroplasty, and complications occur with placement of unicompartmental knee devices. This article discusses proper and improper implantation techniques and provides technical guidance and suggestions for improving the outcomes of unicompartmental knee arthroplasty.

Arthroplasty, Replacement, Knee↗

Human periprosthetic tissues implanted in severe combined immunodeficient mice respond to gene transfer of a cytokine inhibitor.

BACKGROUND: Periprosthetic tissue formation and local inflammation that are associated with wear debris contribute to the pathogenesis of aseptic loosening of a prosthesis. This study evaluated a retrovirus-mediated gene therapy with use of a novel xenograft-based animal model. METHODS: Human periprosthetic tissues obtained from patients during revision arthroplasty performed because of aseptic loosening of a prosthetic joint were transplanted into the left quadriceps and paravertebral muscles of severe combined immunodeficient (SCID) mice. The engrafted tissues were recovered seven, fifteen, or thirty days after implantation for histological and molecular analyses. The periprosthetic tissues were incubated with retroviruses encoding for human interleukin-1 receptor antagonist (hIL-1Ra) or bacteria beta-galactosidase (LacZ) at 37 degrees C for three hours prior to implantation to evaluate their responses to gene modification. RESULTS: The human periprosthetic tissues were well accepted in SCID mice for up to thirty days, with angiogenesis occurring in the majority of the implanted tissue sections. The histological appearance was consistent between the recovered graft tissue and the original donor tissue. Strong expression of interleukin-1, tumor necrosis factor, and interleukin-6 was detected in the xenografts with use of immunohistochemical stains. Histological analysis revealed that interleukin-1 receptor antagonist gene modification significantly decreased the total number of inflammatory cells (p < 0.01) in engrafted human tissue containing implant wear debris. Real-time reverse transcription-polymerase chain reaction and immunohistochemical staining showed declining expression levels of interleukin-1 and tumor necrosis factor following interleukin-1 receptor antagonist gene transfer in comparison with LacZ-transduced or virus-free controls. CONCLUSIONS: Human periprosthetic tissue can survive in the SCID mouse host for up to thirty days and responds to the interleukin-1 receptor antagonist gene transfer with the amelioration of inflammation.

Aged↗

Simple techniques for passing suture through bone.

Sutures often must be passed through bone tunnels to repair soft tissue or bone. Three easy, inexpensive, and time-saving suture-passing techniques are described in this article. These techniques, which involve using 1 of 3 readily available instruments (Angiocath, Hewson suture retriever, Keith needle), can be applied in many different orthopedic surgical procedures and may save much time and aggravation in the operating room.

Bone and Bones↗

The use of a constrained acetabular component for recurrent dislocation.

The poor results of surgical treatment of chronic instability after total hip arthroplasty (THA) led to the development of a constrained acetabular component. In this study, 87 constrained THAs implanted for recurrent instability were reviewed retrospectively. Eighty-five hips were available for follow-up evaluation, with an average follow-up period of 58 months. These 85 hips were evaluated at a minimum of 3 years. Two recurrent dislocations were seen, caused by dissociation of the liner from the shell. Four acetabular components and 1 femoral component were revised. Overall, a 2.4% dislocation rate and an 8.2% revision rate were seen. The recurrent dislocation rate of 2.4% represents a significant improvement over other methods reported. Repeat dislocation was only seen in dissociation of cemented liners into well-fixed shells. We do not recommend this mode of fixation.

Acetabulum↗

Cement pressurization after provisional repair of femoral cortical defects.

Cortical defects are common and problematic in cemented revision hip arthroplasty. Extruded cement can cause thermal injury, pain, and impingement. Decreased cement pressure limits bony interdigitation and leads to loosening. Historically, surgeons have used a finger to contain cement and improve pressure, and decrease porosity, but, with large or multiple defects, fingers are ineffective. Novel solutions--such as wrapping foil suture packaging or half a syringe barrel around the defects--have been previously published. In the study reported here, we used modern cementing techniques, continuous pressure monitoring, and porosity calculations to analyze the utility of the 3 provisional defect-fixation techniques. The foil and the hemisyringe worked as well as a finger (P > .05). All 3 techniques enhanced pressurization and maintained the porosity reduction. Although manually pressurizing cement and feeling resistance provide the surgeon with more tactile feedback, using the gun and a proximal adapter was more effective in improving pressure. Using these provisional defect-fixation techniques as well as a cement gun and proximal adapter can improve cement pressure and decrease porosity. These techniques are particularly useful with large or multiple cortical defects encountered in revision arthroplasty or total hip arthroplasty after open reduction.

Animals↗

Pull-out and shear failure strengths of arthroscopic meniscal repair systems.

Meniscal repair is common and recommended in young patients. Suture techniques and fixation devices were developed for stronger, more facile repairs. Three devices (T-Fix, Meniscal Staple, Meniscus Arrow) were biomechanically compared to horizontal PDS suture. Peripheral tears were created in porcine menisci and repaired using the manufacturer's technique. An Instron was used to distract the menisci at 50 mm/min in axial-pullout and longitudinal shear loads. Load to failure curves and peak failure loads were noted. Load to failure in axially loaded pull-out mode was: Staple, 4.195+/-3.70 N; Arrow, 39.755+/-11.37 N; T-Fix, 45.892+/-13.99 N; Suture, 107.65+/-22.37 N. Analysis of variance with post hoc testing revealed Staple failure at lower load than all devices and Suture failure at higher loads than all devices; Arrow and T-Fix were similar. The data varied significantly from that obtained in shear. Shear loads to failure were: Staple, 8.39+/-8.62 N; Arrow, 27.67+/-14.33 N; T-Fix, 57.47+/-17.05 N; Suture, 64.15+/-17.05 N. Analysis of variance, power analysis, and pair-wise multiple comparisons revealed significant differences between: Suture and Staple, Suture and Arrow, and T-Fix and Staple. No differences were noted between Suture and T-Fix, T-Fix and Arrow, or Arrow and Staple. In pullout, Suture and T-Fix maintained better apposition at low loads. As load increased, the menisci separated until device failure. Arrows allowed low load separation but held tissue until failure. Staples failed at low load. For shear, the menisci attempted to reorient parallel to the force. The devices failed in a pull-slide pattern. Suture failed by pull-through. Meniscal repair devices are easy to use and may provide resistance to shear and pull out. The resistance to pullout loads was very different than the resistance to longitudinal shear loads.

Analysis of Variance↗

Press-fit stability of uncemented hemispheric acetabular components: a comparison of three porous coating systems.

Cementless acetabular components require good initial fixation to allow bony in-growth. The initial press-fit stability, important for designs that do not rely on supplemental fixation, was examined for three designs with different porous coating systems: beads, fiber mesh, and plasma spray. The ability to withstand tangential loads was determined (maximum rim loads: 122-1730 N). The plasma-sprayed acetabular cups withstood the greatest tangential load within the specified range of motion of 150 microm (P<0.01). Differences in surface preparation of titanium acetabular cups may significantly affect the initial stability of the implants in rim loading.

Acetabulum↗

Effect of external sequential compression devices on femoral venous blood flow.

Sequential compression devices are used to reduce venous stasis and deep venous thrombosis after joint replacement. Thigh-length, calf-length, and foot compression devices were compared in using ultrasonography after unilateral knee arthroplasty. Simulated muscle activity via active ankle motion was also evaluated. Blood flow volume and velocity were recorded above and below the saphenous vein bifurcation, the division of the superficial and deep systems, allowing evaluation of each. Volume and velocity increased in the superficial and deep systems with all devices. A control group was evaluated to determine differences related to age and surgery. The devices performed similarly in the volunteers. However, active motion performed better than any device. Thus, unlike young, healthy patients, muscle activity alone in the operative population was unreliable in increasing blood flow. Thigh-length, calf-length, and foot compression devices are are effective at increasing femoral blood flow volume and velocity in the deep and superficial venous systems after total knee arthroplasty.

Aged↗