Biomedical subjects

F H Fu

Publications and source records attributed to F H Fu.

At least 73 records · Page 4Linked to original sources

PubMed1997

[Gene transfer into the patellar tendon of rabbits: a preliminary study of locoregional expression of growth factors].

Growth factors have the potential to enhance native repair responses in ligamentous and meniscal lesions. However, methods for applying these cytokines to sites of injury for extended periods are lacking. We suggest that local transfer of genes which encode the relevant healing factors merits investigation as a potential solution to this problem. In the present study different viral vectors and liposomes were evaluated for their ability to deliver genes to cells of ligamentous and meniscal origin. The anterior (ACL) and posterior (PCL) cruciate ligaments and the medial collateral ligament (MCL), semitendinosus tendon, patellar tendon, and menisci were removed from New Zealand white rabbits Cells grown from these tissues were then investigated for their susceptibility to genetic alteration by these vectors. Based upon the ability of these vectors to convert cells in culture to a lacZ(+) phenotype, adenovirus was the most effective vector in short-term experiments. However, expression was transient. Although retrovirus gave lower initial transduction efficiencies, the percentage of transduced cells was increased by the use of the selectable marker gene neo(r). Cells infected with adeno-associated virus containing the neo(r)-gene were also selected in this way. Liposomes showed low efficiency of gene transfer and expression. In an in vivo marker study we injected adenovirus into the rabbit patellar tendon. Transduced cells were observed mainly in the subsynovial layer at a declining frequency over a 6-week period. The allogeneic transplantation of retrovirally-transduced fibroblasts into the patellar tendon resulted in a greater number of transduced cells. Although the number of lacZ(+) cells declined with time, positive cells were still present 6 weeks after transplantation. Furthermore, the transplanted cells, unlike cells transduced in situ with adenovirus, migrated from the injection site and integrated into the crimp of the tendon.

Adenoviridae↗

PubMed1997

Evaluation of the effect of joint constraints on the in situ force distribution in the anterior cruciate ligament.

The function of the anterior cruciate ligament was investigated for different conditions of kinematic constraint placed on the intact knee using a six-degree-of-freedom robotic manipulator combined with a universal force-moment sensor. To do this, the in situ forces and force distribution within the porcine anterior cruciate ligament during anterior tibial loading up to 100 N were compared at 30, 60, and 90 degrees of flexion under: (a) unconstrained, five-degree-of-freedom knee motion, and (b) constrained, one-degree-of-freedom motion (i.e., anterior translations only). The robotic/universal force-moment sensor testing system was used to both apply the specified external loading to the intact joint and measure the resulting kinematics. After tests of the intact knee were completed, all soft tissues except the anterior cruciate ligament were removed, and these motions were reproduced such that the in situ force and force distribution could be determined. No significant differences in the magnitude of in situ forces in the anterior cruciate ligament were found between the unconstrained and constrained testing conditions. In contrast, the direction of in situ force changed significantly; the force vector in the unconstrained case was more parallel with the direction of the applied tibial load. In addition, the distribution of in situ force between the anteromedial and posterolateral bundles of the ligament was nearly equal for all flexion angles for the unconstrained case, whereas the anteromedial bundle carried higher forces than the posterolateral bundle at both 60 and 90 degrees of flexion for the constrained case. This demonstrates that the constraint conditions placed on the joint have a significant effect on the apparent role of the anterior cruciate ligament. Specifically, constraining joint motion to one degree of freedom significantly alters both the direction and distribution of the in situ force in the ligament from that observed for unconstrained joint motion (five degrees of freedom). Furthermore, the changes observed in the distribution of force between the anteromedial and posterolateral bundles for different constraint conditions may help elucidate mechanisms of injury by providing new insight into the response of the anterior cruciate ligament to different types of external knee loading.

Animals↗

PubMed1997

In situ forces in the anterior cruciate ligament and its bundles in response to anterior tibial loads.

The anterior cruciate ligament has a complex fiber anatomy and is not considered to be a uniform structure. Current anterior cruciate ligament reconstructions succeed in stabilizing the knee, but they neither fully restore normal knee kinematics nor reproduce normal ligament function. To improve the outcome of the reconstruction, it may be necessary to reproduce the complex function of the intact anterior cruciate ligament in the replacement graft. We examined the in situ forces in nine human anterior cruciate ligaments as well as the force distribution between the anteromedial and posterolateral bundles of the ligament in response to applied anterior tibial loads ranging from 22 to 110 N at knee flexion angles of 0-90 degrees. The analysis was performed using a robotic manipulator in conjunction with a universal force-moment sensor. The in situ forces were determined with no device attached to the ligament, while the knee was permitted to move freely in response to the applied loads. We found that the in situ forces in the anterior cruciate ligament ranged from 12.8 +/- 7.3 N under 22 N of anterior tibial load applied at 90 degrees of knee flexion to 110.6 +/- 14.8 N under 110 N of applied load at 15 degrees of flexion. The magnitude of the in situ force in the posterolateral bundle was larger than that in the anteromedial bundle at knee flexion angles between 0 and 45 degrees, reaching a maximum of 75.2 +/- 18.3 N at 15 degrees of knee flexion under an anterior tibial load of 110 N. The magnitude of the in situ force in the posterolateral bundle was significantly affected by knee flexion angle and anterior tibial load in a fashion remarkably similar to that seen in the anterior cruciate ligament. The magnitude of the in situ force in the anteromedial bundle, in contrast, remained relatively constant, not changing with flexion angle. Significant differences in the direction of the in situ force between the anteromedial bundle and the posterolateral bundle were found only at flexion angles of 0 and 60 degrees and only under applied anterior tibial loads greater than 66 N. We have demonstrated the nonuniformity of the anterior cruciate ligament under unconstrained anterior tibial loads. Our data further suggest that in order for the anterior cruciate ligament replacement graft to reproduce the in situ forces of the normal anterior cruciate ligament, reconstruction techniques should take into account the role of the posterolateral bundle in addition to that of the anteromedial bundle.

Adult↗

PubMed1997

Myoblast-mediated gene transfer to the joint.

Several genetic and acquired pathologic conditions of the musculoskeletal system, such as arthritis and damage to ligament, cartilage, and meniscus, may be amenable to gene therapy. Even though ex vivo gene transfer with synovial cells has been shown to deliver genes encoding for anti-arthritic proteins into the rabbit knee joint, its success has been limited by a transient transgene expression. In this study, data were investigated regarding the use of muscle cells as an alternative gene-delivery vehicle to the joint in newborn rabbit and adult severe combined immunodeficiency mice. We demonstrated that myoblasts were transduced more efficiently than synovial cells with use of the same adenoviral preparation in vitro. After intra-articular injection, the engineered muscle cells adhered to several structures in the joint, including the ligament, capsule, and synovium. In addition, myoblasts fused to form many post-mitotic myotubes and myofibers at different locations of the joint of the newborn rabbit 5 days after the injection. In the knee of the adult mouse, myoblasts fused and expressed the reporter gene for at least 35 days after the injection. The presence of post-mitotic myofibers in the knee joint raises the possibility of long-term expression of the secreted protein. Currently, numerous tissues in the joint (ligament, meniscus, and cartilage) have poor intrinsic healing capacity and frequently need surgical corrections. A stable gene-delivery vehicle to the joint producing proteins that ameliorate these different musculoskeletal conditions may change the clinical implications of these pathologies.

Adenoviridae↗

PubMed1997

[Virally mediated gene transfer in the patellar tendon. An experimental study in rabbits].

Growth factors have the potential to enhance native repair responses in ligamentous and meniscal lesions. However, methods for applying these cytokines to sites of injury for extended periods are lacking. We suggest that local transfer of genes that encode the relevant healing factors merits investigation as a potential solution to this problem. In the present study, different viral vectors and liposomes are evaluated for their ability to deliver genes to cells of ligamentous and meniscal origin. The ACL, PCL, MCL, semitendinosus tendon, patellar tendon, and menisci were harvested from New Zealand white rabbits. Cells grown from these tissues were then investigated for their susceptibility to genetic alteration by these vectors. Based upon the ability of these vectors to convert cells in culture to a lacZ(+) phenotype, adenovirus was the most effective vector in short-term experiments. However, expression was transient. Although retrovirus gave lower initial transduction efficiencies, the percentage of transduced cells could be increased by the use of the selectable marker gene neo(r). Cells infected with adeno-associated virus containing the neor-gene could also be selected in this way. Liposomes showed low efficiency of gene transfer and expression. In an in vivo marker study, we injected adenovirus into the rabbit patellar tendon. Transduced cells could be observed preferentially in the subsynovial layer at a declining frequency over a 6-week period. The allogeneous transplantation of retrovirally transduced fibroblasts into the patellar tendon resulted in a greater number of transduced cells. Although the number of lacZ(+) cells declined with time, positive cells were still present 6 weeks after transplantation. Furthermore, the transplanted cells, unlike cells transduced in situ with adenovirus, migrated from the injection site and integrated into the crimp of the tendon.

Adenoviridae↗

PubMed1997

Gene transfer to the patellar tendon.

Growth factors have the potential to enhance native repair responses in ligamentous lesions. However, methods for applying these cytokines to sites of injury for extended periods are lacking. We suggest that local transfer of genes which encode the relevant healing factors merits investigation as a potential solution to this problem. In the present study, the retroviral vectors MFG lacZ and BAG lacZ neo(r) and adenovirus LacZ were evaluated for their ability to deliver genes to cells of ligamentous origin. The posterior and anterior cruciate ligaments, medial collateral ligament, semitendinosus tendon and patellar tendon were harvested from New Zealand white rabbits. Cells grown from these tissues were then investigated for their susceptibility to genetic alteration by these vectors in vitro. Based upon their ability to convert cells in culture to a lacZ(+) phenotype, adenovirus was the most effective vector in short-term experiments. However, expression was transient. Although retrovirus gave lower initial transduction efficiencies, the percentage of transduced cells could be increased by the use of the selectable marker gene neo(r). In an in vivo marker study, we injected adenovirus into the rabbit patellar tendon. Transduced cells could be observed preferentially in the subsynovial layer at a declining frequency over a 6-week period. The allogeneic transplantation of in vitro retrovirally transduced fibroblasts into the patellar tendon resulted in a greater number of transduced cells. Although the number of lacZ(+) cells declined with time, positive cells were still present 6 weeks after transplantation. Furthermore, the transplanted cells, unlike cells transduced in situ with adenovirus, migrated from the injection site and integrated into the crimp of the tendon.

Adenoviridae↗

PubMed1997

Tunnel expansion following anterior cruciate ligament reconstruction: a comparison of hamstring and patellar tendon autografts.

Thirty patients having had anterior cruciate ligament (ACL) reconstruction with bone-patellar tendon-bone (BPTB) autograft and thirty patients having had ACL reconstruction with hamstring (HS) autograft were enrolled. All procedures were performed using an endoscopic technique with identical postoperative rehabilitation, such that the only variable was the type of graft and its fixation. Lateral and 45 degrees posteroanterior (PA) weightbearing radiographs were performed in each patient at 6-12 (mean 9) months postoperatively in the HS group and 9-22 (mean 13) months postoperatively in the PT group. The sclerotic margins of the tunnel were measured at the widest dimension of the tunnel by a single observer and were compared with the initially drilled tunnel size after correction for radiographic magnification. For the BPTB group, all bone plugs appeared to be incorporated radiographically. On the femoral side, the bone plug was incorporated at the roof of the intercondylar notch, such that no tunnel measurement could be made. Well-defined sclerotic margins were always present at the tibial and femoral tunnels for the HS group and at the tibial tunnel for the BPTB group. The mean percentage increase in tunnel size in the PA view was 9.7%+/-14.7% for the BPTB tibial tunnel, 20.9%+/-13.4% for the HS tibial tunnel, and 30.2%+/-17.2% for the HS femoral tunnel. The mean percentage increase in tunnel size in the lateral view was 14.4%+/-16.1% for the BPTB tibial tunnel, 25.5%+/-16.7% for the HS tibial tunnel, and 28.1%+/-14.7% for the HS femoral tunnel. The difference in HS and BPTB tibial tunnel expansion on both the PA and lateral views was statistically significant (P = 0.003 and P = 0.01, respectively). Inter-observer variability was excellent with an intra-class correlation coefficient of 0.92. Tunnel expansion was significantly greater following ACL reconstruction using HS autografts than in those using BPTB autografts. The points of fixation for the HS grafts are at a greater distance from the normal insertion site and biomechanical point of action of the ACL than the points of fixation for BPTB grafts. We believe that this greater distance creates a potentially larger force moment during graft cycling which may lead to greater expansion of bone tunnels.

Adolescent↗

PubMed1997

Arthroscopic posterior cruciate ligament reconstruction.

Operative treatment of posterior cruciate ligament (PCL) injury is becoming more common as understanding of the natural history of the untreated PCL-deficient knee increases and the surgical techniques improve. The current recommendations for surgical reconstruction include patients with multiple ligament injuries and patients with isolated grade III PCL injuries. An understanding of the anatomy and biomechanics of the PCL is essential for successful reconstruction. This article presents a reproducible surgical technique for arthroscopically assisted PCL reconstruction.

Arthroscopy↗

PubMed1997

The effect of anterior cruciate ligament graft fixation site at the tibia on knee stability: evaluation using a robotic testing system.

Despite its current popularity and relative success, endoscopic reconstruction of the anterior cruciate ligament (ACL) using a bone-patellar tendon-bone (BPTB) graft has not yet been perfected. Using a recently developed robotic/UFS testing system, we assessed the overall stability of porcine knees following ACL reconstruction with different sites of tibial graft fixation--proximal, central, and distal. Testing of the intact knee was performed first to determine the normal anterior-posterior (A-P) displacements and in situ forces of the ACL under 110 N of anterior tibial loading of 30 degrees, 60 degrees, and 90 degrees of knee flexion. The knee was then reconstructed with a BPTB autograft, and the distal end of the graft was fixed sequentially at three different locations in each specimen--proximal, central, distal. A-P testing was repeated for each fixation site, and the resulting knee kinematics and the in situ forces of the grafts were compared to the intact case. The site of tibial fixation was demonstrated to have a significant effect on the resulting anterior displacement and internal rotation of the tibia as well as the in situ forces of the graft. Proximal fixation produced the most stable knee (A-P displacements reduced to 120% of intact at 30 degrees and 170% at 90 degrees), becoming significantly less stable with more distal fixation. These results suggest that proximal graft fixation may provide the most acute stability of the reconstructed knee.

Animals↗

PubMed1997

The effects of cryotherapy on muscle damage in rats subjected to endurance training.

Sixty 60-day-old Sprague-Dawley male rats were subjected to exhaustive and non-exhaustive exercise treatment over a period of 3, 5 and 7 weeks. Moderate exercise consisted of running on the treadmill at 10% grade at 10 m/min for 20 min for 5 days per week, while exhaustive running consisted of running at 10% grade at 15 m/min with an increase of 5 m/min every 5 min for 5 days per week. Half of the exercised rats were subjected to immersion in 4 degrees C water for 5 min after each exercise bout. Histological analyses of the gastrocnemius showed that ultrastructural damage of myofibrils occurred after 5 weeks of exhaustive running and 7 weeks of moderate running. With post-exercise immersion in 4 degrees C water for 5 min, the occurrence of ultrastructural damage advanced by 2 weeks in both treatments. It was concluded that the application of cryotherapy to the exercise groups was deleterious. Muscle damage occurred earlier in the treatment group and the degree of damage was also more serious over the same time period. This study supports the recommendation that the use of cryotherapy to reduce pain and haematoma formation should be coupled with rest for at least 48 hours.

Actin Cytoskeleton↗

PubMed1997

Monoclonal antibody 3F3 against conformational epitope of Torpedo acetylcholinesterase.

AIM: To study the type of epitope of native Torpedo acetylcholinesterase (AChE) directed by its monoclonal antibody (McAb) 3F3. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used for the assay of the reaction between antigen and antibody. RESULTS: McAb 3F3 immunoreacted well with the native AChE, but not with the reduced- and alkylated-AChE (RA-AChE) at all. Soman did not interfere the binding of 3F3 with AChE molecule. The synthesized 24-peptide containing the active serine residue of the AChE active center did not react with McAb 3F3. CONCLUSION: 3F3 is a monoclonal antibody against the conformational epitope of Torpedo AChE active center, but dose not occupy the active serine residue of the enzyme.

Acetylcholinesterase↗

PubMed1997

Anionic subsite of active center of Torpedo acetylcholinesterase constructs a part of its conformational epitope.

AIM: To study the structure-activity relationship of Torpedo acetylcholinesterase (AChE) and explore whether the anionic subsite of the active center is a constituent of the conformational epitope of enzyme. METHODS: Using ELISA and enzyme inhibition test to examine the effect of 1-methyl-2-hydroxyiminomethylpyridium chloride (2-PAM), an anionic subsite probe of AChE, on the immunoreactivity between Torpedo AChE and its monoclonal antibody (McAb) 3F3. RESULTS: McAb 3F3 did not react with 2-PAM-AChE complex. 2-PAM decreased the inhibitory rate of McAb 3F3 on AChE in a concentration-dependent fashion, but did not dissociate the McAb 3F3-AChE complex. CONCLUSION: Anionic subsite of the active center of Torpedo AChE constructs a part of its conformational epitope.

Acetylcholinesterase↗

PubMed1997

[Possibilities of gene therapy in traumatic and degenerative articular lesions. Current status of experimental and initial clinical applications].

Soft tissue injuries often represent the greatest clinical problem. Not only do many of the most frequently injured tissues, such as the cruciate ligaments and articular cartilage, have very limited capabilities for spontaneous repair, but they also respond poorly to surgical or non-surgical intervention. In this article we try to define the role of growth factors in these conditions and to outline concepts for future treatment based upon modulation of the native repair response. We suggest that gene transfer could improve the management of such injuries, particularly when used as vehicles for the targetted delivery of growth factors.

Animals↗

PubMed1996

Temperature changes in the knee joint during arthroscopic surgery.

Normal joint conditions are altered during arthroscopic surgery, and these changes have uncertain ultrastructural and biomechanical effects on articular cartilage. Experimental studies have shown that temperature variations affect the biomechanical properties of articular cartilage. We documented the temperature of the knee joint in 40 patients at the beginning and end of an arthroscopic procedure (anterior cruciate ligament reconstruction or meniscectomy). The intra-articular measurements were obtained using a digital thermometer connected to a sterile stainless steel probe. Correlation coefficients and linear regression techniques were used to determine which variables are independent predictors of joint temperature at the end of surgery. The mean knee joint temperature before surgery was 35.1 degrees +/- 1.0 degrees C and at the end of surgery 24.6 degrees +/- 1.5 degrees C. The joint temperature at the end of surgery was significantly affected by the temperature of the saline irrigant used and the length of arthroscopic procedure. The clinical implications of our findings must be clarified in animal models.

Adolescent↗

PubMed1996

Mechanical properties of the long head of the biceps tendon.

In this study, the geometric and mechanical properties of the long head of the biceps tendon were determined in order to elucidate its role in shoulder stability. We used a laser-micrometer system to measure the cross-sectional area and shape of seven fresh-frozen tendons at three levels: proximal, middle, and distal levels. The cross-sectional areas were found to be 22.7 +/- 9.3 mm2, 22.7 +/- 3.5 mm2, and 10.8 +/- 2.7 mm2, respectively. While statistically significant differences could not be demonstrated between the magnitudes of the areas, a consistent difference in shape was noted between the proximal and middle levels, the tendon being flatter as it progressed over the humeral head and more triangular as it passed through the bicipital groove. We then performed cyclic relaxation tests and uniaxial tensile testing of the tendons which revealed a cyclic stress relaxation of 18 +/- 4% over ten cycles. All tensile failures occurred within the mid-portion of the tendon substance. Additionally, the modulus was calculated between 3% and 6% strain and found to be 421 +/- 212 MPa, while the ultimate tensile strength, ultimate strain, and strain energy density were 32.5 +/- 5.3 MPa, 10.1 +/- 2.7 %, and 1.9 +/- 0.4 MPa, respectively. These mechanical properties of the long head of the biceps tendon are of the same order of magnitude as tendons from other joints. The high stiffness of this tendon indicates that it has an ability to support the large load transferred to it by the muscle and to act as a humeral head depressor.

Adult↗

PubMed1996

Knee joint proprioception: a comparison between female intercollegiate gymnasts and controls.

The role of proprioception as a protective mechanism has gained interest in recent years. From the clinical standpoint, several studies have dealt with ways to enhance proprioception following surgery and during rehabilitation. If kinesthesia (ability to detect passive motion) can be enhanced as a consequence of long-term athletic training, such training must be included as a part of the rehabilitation process to protect the patient from reinjury. Consequently, the purpose of this study was to compare the kinesthetic knee pattern between trained gymnasts and healthy nongymnasts. The proprioception testing device (PTD) was used to evaluate knee kinesthesia. From 45 degrees of flexion, the knee was passively extended with the PTD. The device was stopped by the subject when this passive motion was detected. Fifteen healthy college-age female gymnasts (mean age 19.3 years) and 30 normal volunteers (mean age 20.7 years) comprised our study sample. A one-way analysis of variance (ANOVA) was used to compare the mean values of the dominant gymnastic knee to the dominant knee in the control group. Results revealed statistically significant mean differences between the trained gymnastic group and the untrained control group (F1.34(.95) = 7.17, P = 0.011). The results of this study suggest that extensive training has a positive influence on knee kinesthesia in addition to increasing muscle tone. According to the findings of this and other studies, highly trained athletes possess enhanced neurosensory pathways which are speculated to develop as a result of long-term athletic training. Although definite conclusions cannot be made from our investigation, prospective studies can determine the true role of athletic training in proprioceptive patterns.

Adolescent↗

PubMed1996

Prospects for gene therapy in sports medicine.

For the orthopedic sports medicine physician soft tissue injuries often present the greatest clinical problems. Not only do many of the most frequently injured tissues, such as the cruciate ligaments and articular cartilage, have very limited capabilities for spontaneous repair, but they also respond poorly to surgical or nonsurgical intervention. In this article we try to define the role of growth factors in these conditions and to outline concepts for future treatment based upon modulation of the native repair response. We suggest that gene transfer could improve the management of such injuries, particularly when used as vehicles for the targeted delivery of growth factors. The concept of gene therapy in orthopedic sports medicine can be extended to include disorders that present as laxity or mechanical weakness of ligaments. We speculate that subtle genetic differences between individuals may account for those who appear to be injury prone. In these cases it is likely that genes encoding the structural macromolecules of the matrix are defective. Local gene supplementation in such cases could be useful in the future.

Athletic Injuries↗

PubMed1996

A combined robotic/universal force sensor approach to determine in situ forces of knee ligaments.

We developed a system that uses a 6-degree-of-freedom (6-DOF) robotic manipulator combined with a 6-DOF force-moment sensor and a control system. The system is used to find and record the passive knee flexion path for controlling the knee flexion positions. It is also used to strain a knee structure by finding a multiple-DOF path in response to specific joint loading, e.g. anterior-posterior tibial force application. It is additionally used to measure in-situ forces in ligaments by recording differences in forces and moments when repeating a prerecorded path, both before and after removal of the ligament of interest. Example applications are included in the study.

Animals↗