Andrew L. Wallace

Structural Properties of the Intact and the Reconstructed Coracoclavicular Ligament Complex

Numerous procedures have been described for the operative management of acromioclavicular joint injuries, but surprisingly little information is available on the ultimate mechanical behavior of the native coracoclavicular ligament complex or on the various methods of reconstruction. We tested 19 fresh-frozen cadaveric bone-ligament-bone preparations of the coracoclavicular ligament in uniaxial tension at 25 mm/min until failure. Seven specimens were left intact, six had the trapezoid ligament sectioned, and six had the conoid ligament sectioned. Reconstruction of the coracoclavicular ligament was achieved using coracoacromial ligament transfers, woven polyester slings, suture anchors, and Bosworth screws; all reconstructions were also tested to failure. The intact coracoclavicular ligament failed by avulsion or midsubstance tear at 500 (134) N, with a stiffness of 103 (30) N/mm and elongation to failure of 7.7 (1.9) mm. There was no significant difference between the contributions of the conoid or trapezoid ligaments in this loading configuration. Coracoclavicular slings and suture anchors provided strength similar to that of the coracoclavicular ligament, but with significantly greater deformations (14 to 26 mm). Screw fixation resulted in comparable stiffness and superior strength to the coracoclavicular ligament, but only if bicortical purchase was obtained. Coracoacromial ligament transfers were the weakest and least stiff, and augmentation with another form of coracoclavicular fixation is recommended. These results provide a useful baseline for comparison of the initial performance of reconstructive techniques with the performance of the native coracoclavicular ligament.

A Biomechanical Comparison of Single and Double-Row Fixation in Arthroscopic Rotator Cuff Repair

BACKGROUND The optimal method for arthroscopic rotator cuff repair is not yet known. The hypothesis of the present study was that a double-row repair would demonstrate superior static and cyclic mechanical behavior when compared with a single-row repair. The specific aims were to measure gap formation at the bone-tendon interface under static creep loading and the ultimate strength and mode of failure of both methods of repair under cyclic loading. METHODS A standardized tear of the supraspinatus tendon was created in sixteen fresh cadaveric shoulders. Arthroscopic rotator cuff repairs were performed with use of either a double-row technique (eight specimens) or a single-row technique (eight specimens) with nonabsorbable sutures that were double-loaded on a titanium suture anchor. The repairs were loaded statically for one hour, and the gap formation was measured. Cyclic loading to failure was then performed. RESULTS Gap formation during static loading was significantly greater in the single-row group than in the double-row group (mean and standard deviation, 5.0 +/- 1.2 mm compared with 3.8 +/- 1.4 mm; p < 0.05). Under cyclic loading, the double-row repairs failed at a mean of 320 +/- 96.9 N whereas the single-row repairs failed at a mean of 224 +/- 147.9 N (p = 0.058). Three single-row repairs and three double-row repairs failed as a result of suture cut-through. Four single-row repairs and one double-row repair failed as a result of anchor or suture failure. The remaining five repairs did not fail, and a midsubstance tear of the tendon occurred. CONCLUSIONS Although more technically demanding, the double-row technique demonstrates superior resistance to gap formation under static loading as compared with the single-row technique. CLINICAL RELEVANCE A double-row reconstruction of the supraspinatus tendon insertion may provide a more reliable construct than a single-row repair and could be used as an alternative to open reconstruction for the treatment of isolated tears.

Growth factor-based therapies provide additional benefit beyond physical therapy in resistant elbow tendinopathy: a prospective, single-blind, randomised trial of autologous blood injections versus platelet-rich plasma injections

Background Growth factor technologies are increasingly used to enhance healing in musculoskeletal injuries, particularly in sports medicine. Two such products; platelet-rich plasma (PRP) and autologous blood, have a growing body of supporting evidence. No previous trial has directly compared the efficacy of these two methods. Hypothesis Growth factor administration improves tissue regeneration in patients who have failed to respond to conservative therapy. Study design A prospective, double-blind, randomised trial. Methods Elbow tendinopathy patients who had failed conservative physical therapy were divided into two patient groups: PRP injection (N=80) and autologous blood injection (ABI) (N=70). Each patient received two injections at 0 and 1 month. Patient-related tennis elbow evaluation (PRTEE) was recorded by a blinded investigator at 0, 1, 3 and 6 months. The main outcome measure was PRTEE, a validated composite outcome for pain, activities of daily living and physical function, utilising a 0–100 scale. Results At 6 months the authors observed a 66% success rate in the PRP group versus 72% in the ABI group, p=NS. There was a higher rate of conversion to surgery in the ABI group (20%) versus the PRP group (10%). Conclusion In patients who are resistant to first-line physical therapy such as eccentric loading, ABI or PRP injections are useful second-line therapies to improve clinical outcomes. In this study, up to seven out of 10 additional patients in this difficult to treat cohort benefit from a surgery-sparing intervention.

Proteomic analysis of articular cartilage shows increased type II collagen synthesis in osteoarthritis and expression of inhibin betaA (activin A), a regulatory molecule for chondrocytes.

We show that proteomic analysis can be applied to study cartilage pathophysiology. Proteins secreted by articular cartilage were analyzed by two-dimensional SDS-PAGE and mass spectrometry. Cartilage explants were cultured in medium containing [35S]methionine/cysteine to radiolabel newly synthesized proteins. To resolve the cartilage proteins by two-dimensional electrophoresis, it was necessary to remove the proteoglycan aggrecan by precipitation with cetylpyridinium chloride. 50–100 radiolabeled protein spots were detected on two-dimensional gels of human cartilage cultures. Of 170 silver-stained proteins identified, 19 were radiolabeled, representing newly synthesized gene products. Most of these were known cartilage constituents. Several nonradiolabeled cartilage proteins were also detected. The secreted protein pattern of explants from 12 osteoarthritic joints (knee, hip, and shoulder) and 14 nonosteoarthritic adult joints were compared. The synthesis of type II collagen was strongly up-regulated in osteoarthritic cartilage. Normal adult cartilage synthesized little or no type II collagen in contrast to infant and juvenile cartilage. Potential regulatory molecules novel to cartilage were identified; pro-inhibin βA and processed inhibin βA (which dimerizes to activin A) were produced by all the osteoarthritic samples and half of the normals. Connective tissue growth factor and cytokine-like protein C17 (previously only identified as an mRNA) were also found. Activin induced the tissue inhibitor for metalloproteinases-1 in human chondrocytes. Its expression was induced in isolated chondrocytes by growth factors or interleukin-1. We conclude that type II collagen synthesis in articular cartilage is down-regulated at skeletal maturity and reactivated in osteoarthritis in attempted repair and that activin A may be an anabolic factor in cartilage.

Resurfacing of the glenoid in total shoulder arthroplasty : A comparison, at a mean of five years, of prostheses inserted with and without cement

BACKGROUND Clinically evident loosening of a glenoid component inserted with cement in total shoulder arthroplasty is infrequent, but radiographic changes that indicate loosening at the implant-bone interface are common and have been associated with functional limitation. We compared the results of total shoulder arthroplasties in which the glenoid implant had been inserted with cement with those of arthroplasties in which a bone-ingrowth glenoid implant had been inserted without cement. METHODS The results of eighty-six consecutive total shoulder arthroplasties, performed by the same surgeon, were retrospectively reviewed between four and seven years after the operation. Fifty-eight shoulders in which the primary glenoid implant was in situ were assessed with use of the Simple Shoulder Test and Short Form-36 questionnaires, clinical examination, and fluoroscopic imaging of the glenoid implant-bone interface. Thirty-two of the glenoid components had been fixed with cement and twenty-six, without cement. RESULTS Complications occurred in 16 percent (fourteen) of the eighty-six shoulders, and 9 percent (eight) of the shoulders needed a revision operation. None of the revisions were done because of loosening of the glenoid component. Five of the eight revisions involved implants that had been inserted without cement. Three of these implants were revised because of early instability and two, because the polyethylene component had separated from the metal tray of the glenoid implant. With the numbers available, we could not detect any significant differences between the groups with respect to pain, range of motion, function of the shoulder, or general health. Radiographic analysis demonstrated a high level of interobserver agreement (kappa = 0.89). Radiolucent lines were observed after 41 percent (thirteen) of the thirty-two arthroplasties performed with cement compared with 23 percent (six) of the twenty-six arthroplasties performed without cement. The proportion of implants classified as probably loose was approximately three times greater in the group in which cement had been used. Eccentric wear of the posterior rim of the metal tray and focal osteolysis under the metal tray were observed in the group in which the component had been inserted without cement; these findings may indicate a potential for progression of radiographic loosening with increased durations of follow-up. CONCLUSIONS We concluded that, despite the higher rate of early complications, the intermediate-term outcomes of arthroplasties in which the glenoid implant is inserted without cement are comparable with those of arthroplasties with cementing of the glenoid component.

Studying biological tissue with fluorescence lifetime imaging: microscopy, endoscopy, and complex decay profiles

We have applied fluorescence lifetime imaging (FLIM) to the autofluorescence of different kinds of biological tissue in vitro, including animal tissue sections and knee joints as well as human teeth, obtaining two-dimensional maps with functional contrast. We find that fluorescence decay profiles of biological tissue are well described by the stretched exponential function (StrEF), which can represent the complex nature of tissue. The StrEF yields a continuous distribution of fluorescence lifetimes, which can be extracted with an inverse Laplace transformation, and additional information is provided by the width of the distribution. Our experimental results from FLIM microscopy in combination with the StrEF analysis indicate that this technique is ready for clinical deployment, including portability that is through the use of a compact picosecond diode laser as the excitation source. The results obtained with our FLIM endoscope successfully demonstrated the viability of this modality, though they need further optimization. We expect a custom-designed endoscope with optimized illumination and detection efficiencies to provide significantly improved performance.

Mechanical factors in the initiation and propagation of tears of the rotator cuff: QUANTIFICATION OF STRAINS OF THE SUPRASPINATUS TENDON IN VITRO

Differential strain has been proposed to be a causative factor in failure of the supraspinatus tendon. We quantified the strains on the joint and bursal sides of the supraspinatus tendon with increasing load (20 to 200 N) and during 120 degrees of glenohumeral abduction with a constant tensile load (20 to 100 N). We tested ten fresh frozen cadaver shoulders on a purpose-built rig. Differential variable reluctance extensometers allowed calculation of the strain. Static loading to 100 N or more increased strains on the joint side significantly more than on the bursal side. During glenohumeral abduction an increasing and significant difference in strain was measured between the joint and bursal sides of the supraspinatus tendon, which reached a maximum of 10.6% at abduction of 120 degrees. The joint side strain of 7.5% reached values which were previously reported to cause failure. Differential strain causes shearing between the layers of the supraspinatus tendon, which may contribute to the propagation of intratendinous defects that are initiated by high joint side strains.

Intraoperative Assessment of Tibiofemoral Contact Stresses in Total Knee Arthroplasty

The production of polyethylene wear debris in total knee arthroplasty (TKA) is due to multiple factors. In particular, inadequate implant alignment and high bearing surface contact stresses are associated with polyethylene failure. Optimal implant placement and soft tissue balancing may contribute to reducing wear and the production of polyethylene particles. We present a case in which a quantitative technique was used to measure tibiofemoral contact stresses during implantation of a total knee prosthesis in vivo. In a knee with preoperative varus and fixed flexion deformity, medial compartment contact stresses after initial resection were reduced from 14.3 MPa to 11.3 MPa in neutral alignment by additional bone resection. Posterior cruciate release was required to reduce contact stresses further and to provide satisfactory balance between medial and lateral compartments, as determined by the operating surgeon, and was confirmed by the measurement system (3.8 MPa medially; 3.0 MPa laterally). This technique has potential to fine-tune implant positioning and ligament balancing during TKA.

Selection of Potent Inhibitors of Farnesyl-protein Transferase from a Synthetic Tetrapeptide Combinatorial Library

Inhibitors of farnesyl-protein transferase (FPTase) show promise as anticancer agents. Based on the sequence of the protein substrates of FPTase (the CAAX sequence), potent and selective peptidomimetic inhibitors have been developed; these compounds share with the peptide substrate a free thiol and a C-terminal carboxylate. We have used a synthetic tetrapeptide combinatorial library to screen for new leads devoid of these features: the peptides were C-terminally amidated, and no free thiol was included in the combinatorial building blocks. To compensate for this negative bias, an expanded set of 68 amino acids was used, including both L and D as well as many non-coded residues. Sixteen individual tetrapeptides derived from the consensus were synthesized and tested; all were active, showing IC50 values ranging from low micromolar to low nanomolar. The most active peptide, D-tryptophan-D-methionine-D-4-chlorophenylalanine-L-γ-carboxyglutamic acid (Ki = 2 nM), is also very selective showing little inhibitory activity against the related enzyme geranylgeranyl-protein transferase type I (IC50 > 50 μM). In contrast to CAAX-based peptidomimetics, D-tryptophan-D-methionine-D-4-chlorophenylalanine-L-γ-carboxyglutamic acid appeared to mimic the isoprenoid substrate farnesyl diphosphate as determined by kinetic and physical measurements. D-Tryptophan-Dmethionine-D-4-chlorophenylalanine-L-γ-carboxyglutamic acid was a competitive inhibitor of FPTase with respect to farnesyl diphosphate substrate and uncompetitive with respect to CAAX substrate. Furthermore, we demonstrated that FPTase undergoes ligand dependent conformational changes in its circular dichroism spectrum and that D-tryptophan-D-methionine-D-4-chlorophenylalanine-L-γ-carboxyglutamic acid induced a conformational change identical to that observed with farnesyl diphosphate ligand.

Glenoid Rim Fracture in Contact Athletes With Absorbable Suture Anchor Reconstruction

Absorbable suture anchors are widely used in arthroscopic shoulder reconstruction procedures and provide a good solution for stabilization in athletes. In our practice we identified a group of 3 patients who had participated in contact sports and in whom traumatic instability developed. Subluxation of the shoulder followed repair by use of absorbable suture anchors. Each patient had a new injury characterized by a glenoid rim fracture that was not amenable to further arthroscopic reconstruction and was revised by use of a modified Latarjet procedure. All patients successfully returned to contact sports. We conclude that resorption defects resulting from the use of absorbable anchors contribute to an increased risk of rim fracture.