Achilles and tail tendons of perlecan exon 3 null heparan sulphate deficient mice display surprising improvement in tendon tensile properties and altered collagen fibril organisation compared to C57BL/6 wild type mice.

The aim of this study was to determine the role of the perlecan (Hspg2) heparan sulphate (HS) side chains on cell and matrix homeostasis in tail and Achilles tendons in 3 and 12 week old Hspg2 exon 3 null HS deficient (Hspg2Δ3 - ∕Δ3 -) and C57 BL/6 Wild Type (WT) mice. Perlecan has important cell regulatory and matrix organizational properties through HS mediated interactions with a range of growth factors and morphogens and with structural extracellular matrix glycoproteins which define tissue function and allow the resident cells to regulate tissue homeostasis. It was expected that ablation of the HS chains on perlecan would severely disrupt normal tendon organization and functional properties and it was envisaged that this study would better define the role of HS in normal tendon function and in tendon repair processes. Tail and Achilles tendons from each genotype were biomechanically tested (ultimate tensile stress (UTS), tensile modulus (TM)) and glycosaminoglycan (GAG) and collagen (hydroxyproline) compositional analyses were undertaken. Tenocytes were isolated from tail tendons from each mouse genotype and grown in monolayer culture. These cultures were undertaken in the presence of FGF-2 to assess the cell signaling properties of each genotype. Total RNA was isolated from 3-12 week old tail and Achilles tendons and qRT-PCR was undertaken to assess the expression of the following genes Vcan, Bgn, Dcn, Lum, Hspg2, Ltbp1, Ltbp2, Eln and Fbn1. Type VI collagen and perlecan were immunolocalised in tail tendon and collagen fibrils were imaged using transmission electron microscopy (TEM). FGF-2 stimulated tenocyte monolayers displayed elevated Adamts4, Mmp2, 3, 13 mRNA levels compared to WT mice. Non-stimulated tendon Col1A1, Vcan, Bgn, Dcn, Lum, Hspg2, Ltbp1, Ltbp2, Eln and Fbn1 mRNA levels showed no major differences between the two genotypes other than a decline with ageing while LTBP2 expression increased. Eln expression also declined to a greater extent in the perlecan exon 3 null mice (P < 0.05). Type VI collagen and perlecan were immunolocalised in tail tendon and collagen fibrils imaged using transmission electron microscopy (TEM). This indicated a more compact form of collagen localization in the perlecan exon 3 null mice. Collagen fibrils were also smaller by TEM, which may facilitate a more condensed fibril packing accounting for the superior UTS displayed by the perlecan exon 3 null mice. The amplified catabolic phenotype of Hspg2Δ3 - ∕Δ3 - mice may account for the age-dependent decline in GAG observed in tail tendon over 3 to 12 weeks. After Achilles tenotomy Hspg2Δ3 - ∕Δ3 - and WT mice had similar rates of recovery of UTS and TM over 12 weeks post operatively indicating that a deficiency of HS was not detrimental to tendon repair.

Biomechanical comparison of metatarsal head designs in first metatarsophalangeal joint arthroplasty.

BACKGROUND: Arthritis of the metatarsophalangeal (MTP) joint is characterized by loss of MTP joint range of motion (ROM) and pain. Joint arthroplasty is one treatment option, and while results can be satisfactory, there is still room for improvement. The aim was to use cadaveric model to compare the sagittal kinematics and articulating contact properties of 4 different first metatarsal head designs of an MTP joint implant. METHODS: Six cadaveric feet were each prepared with a single modular first MTP joint total arthroplasty. A standard cyclic load, which induced hallux dorsiflexion, was applied and motion measured from high resolution images. Contact behavior was collected simultaneously using a pressure transducer. Data collected compared the native joint with 4 different reconstructed cases. Each reconstructed joint used a different metatarsal-head-component while reusing the same phalangeal component to compare the 4 alternative metatarsal head designs. RESULTS: All reconstructed joints displayed greater ROM compared with the intact joint. Of the 4 metatarsal head components, the grooved, anatomical design demonstrated the greatest dorsiflexion when compared to the standard design, 31.6 degrees (SD ± 8.6 degrees), P < .05. All reconstructed joints displayed contact areas lower than the intact (~50%, P < .001). The grooved metatarsal-head-component experienced the least contact force (P < .015), and the eccentric component underwent the greatest contact pressure (P < .05) when compared to the intact case. CONCLUSIONS: In this study of a first metatarsophalangeal joint replacement design, ROM was shown to be better for the more anatomically designed metatarsal head, while contact properties did not vary across different designs. CLINICAL RELEVANCE: This information may be useful in the development of new metatarsal components.

Mechanical destabilization induced by controlled annular incision of the intervertebral disc dysregulates metalloproteinase expression and induces disc degeneration.

STUDY DESIGN: An investigation of mechanical destabilization of the lumbar ovine intervertebral disc (IVD) inducing IVD degeneration (IVDD) as determined by multiparameter outcome measures (magnetic resonance imaging [MRI], IVD composition, biomechanical testing, gene profiling, immunohistochemistry, and immunoblotting). OBJECTIVE: To assess the effect of IVD mechanical destabilization on matrix protein and metalloproteinase gene expression to investigate the pathophysiological mechanisms of lumbar IVDD. SUMMARY OF BACKGROUND DATA: Several earlier studies have used annular transection to induce IVDD in sheep, but none have optimized or validated the most appropriate lesion size. METHODS: The annulus fibrosus (AF) incision inducing maximal change in IVD biomechanics was applied to L1-L2, L3-L4, and L5-L6 discs in vivo to compare with a sham procedure at 3 months post operation. IVDs were evaluated by MRI, biomechanics, histopathology, proteoglycan and collagen content, gene expression, and aggrecan proteolysis by Western blotting. RESULTS: Significant changes were observed in lesion (6 × 20 mm(2)) compared with sham IVDs at 3 months post operation: reduced disc height on MRI; increased neutral zone in biomechanical testing; depleted proteoglycan and collagen content in the nucleus pulposus (NP) and lesion half of the AF but not in the contralateral AF; increased messenger RNA for collagen I and II, aggrecan, versican, perlecan, matrix metalloproteinase (MMP)-1 & 13, and ADAMTS-5, in the lesion-site AF and NP but not in the contralateral AF. ADAMTS-4 messenger RNA was increased in the lesion-site AF but decreased in the NP. Despite an upregulation in MMPs, there was no change in MMP- or ADAMTS-generated aggrecan neoepitopes in any region of the IVD in lesion or sham discs. CONCLUSION: Lumbar IVDD was reproducibly induced with a 6 × 20 mm(2) annular lesion, with focal dysregulation of MMP gene expression, cell cloning in the inner AF, loss of NP aggrecan, and disc height. Loss of aggrecan from the NP was not attributable to increased proteolysis in the interglobular domain by MMPs or ADAMTS.

A detailed microscopic examination of alterations in normal anular structure induced by mechanical destabilization in an ovine model of disc degeneration.

STUDY DESIGN: Microstructural investigation of anular structure. OBJECTIVE: To reveal the effect of mechanical destabilization on the anular architecture both locally and distantly. SUMMARY OF BACKGROUND DATA: Several longitudinal ovine-induced disc degeneration studies have documented degenerative changes in disc components using histologic, biomechanical, and biochemical approaches; however, changes in intervertebral disc (IVD) microstructure have largely remained neglected. In recent years, the use of structurally relevant section planes has improved our understanding of disc microstructure, including the presence of significant bridging structures radially linking the lamellae. It has been suggested that the translamellar cross-bridges offer a mechanism by which the anular wall can adaptively remodel itself in response to a changing biomechanical microenvironment. METHODS: IVDs harvested from lesion and sham-operated groups of Merino wethers were subjected to en face oblique and vertical sectioning. The macrostructural effect of the destabilization was examined in the vertically sectioned group with conventional histologic techniques. The second group was serially sectioned into 30-µm slices allowing a global examination of the anular microstructure in its fully hydrated state using a differential interference contrast microscope. RESULTS: The previously described induced disc degeneration in the mid-inner anulus fibrosus (AF) and a spontaneous repair process in the outer AF was confirmed. Increased translamellar bridging was observed contralaterally to the lesion in the mechanically destabilized IVD and development of atypical broad bridging elements in the outer lamellae. Structural alterations in the lamellar anchorages to the cartilaginous endplates in destabilized IVDs, including lamellar branching and discontinuities atypical of normal lamellar attachments were also observed. CONCLUSION: The present investigation has offered a glimpse of an anular wall apparently capable of remodeling in response to perturbations in its normal mechanical environment. The translamellar cross-bridges undergo adaptations in structure, in response to altered stresses locally at the anular defect site but also distantly in the contralateral AF in the destabilized disc. It is currently not known whether such changes in anular microarchitecture, however, predispose the anulus to further mechanical damage or have a stabilizing role to play in this structure.

Effect of partial versus complete circumferential repair on flexor tendon strength in cadavers.

PURPOSE: This study investigated the strength of epitendinous repairs covering the palmar half of the tendon circumference only. METHODS: Two hundred porcine tendons were harvested from pig feet and separated into 2 equal groups. Group 1 tendons were sutured with a 2-strand core repair and group 2 tendons were sutured with a 4-strand core repair. Each group was then divided into 5 equal subgroups (n=20). Four of the subgroups were sutured with 1 of the following epitendinous repairs: 50% simple running (50SR), complete simple running (100SR), 50% Silfverskiold (50SK), or complete Silfverskiold (100SK). One sub-group (0C) had no epitendinous repair. The core suture material was 3-0 braided polyester (Tricon; Tyco Healthcare, Dominican Republic), and the circumferential suture material was 6-0 polypropylene (Prolene, Sumerville, NJ). The tendons were mechanically strained to failure, and force data were recorded. RESULTS: The 50SR and 50SK repairs significantly increased the force at 1-mm and 2-mm gap formation of both core repairs. The 50SR and 50SK repairs increased the ultimate force at failure of both core repairs by approximately 20%. Both 50% circumferential (50C) repairs increased repair strength at the points of initial gap formation more than at the point of ultimate force. The 50C repairs were approximately 50% as strong as the 100% circumferential (100C) repairs at 1-mm and 2-mm gap formation and approximately 70% as strong at the ultimate force of failure. CONCLUSIONS: The 50C repairs increased the tensile strength of 2-strand and 4-strand tendon repairs in vitro. The prevention of early gapping was more significant than the increase of strength at failure.

Frog glue enhances rotator cuff repair in a laboratory cadaveric model.

SUMMARY: Rotator cuff tendons are typically reattached to the proximal humerus using transosseous sutures or suture anchors. Their primary mode of failure is at the tendon-bone interface. We investigated the addition of a novel adhesive secreted from a species of Australian frog (Notaden bennetti) to different methods of rotator cuff repair. We hypothesized that the addition of frog glue would increase the strength of the repaired rotator cuff construct. Three techniques were used to repair 42 fresh frozen sheep infraspinatus tendons with a mattress stitch configuration: transosseous sutures; 2 traditional metallic suture anchors with 1 suture per anchor, and 2 knotless metallic anchors with 1 suture per anchor. In each group, 7 shoulders were repaired with the addition of frog glue to the infraspinatus "footprint," whereas 7 were used as control with no adhesive. Failure occurred in all constructs at the tendon-bone-suture interface. Repair with suture anchors was stronger than with sutures through bone (P < .05). Frog glue significantly increased the load to failure, total energy required for failure, and maximum energy at failure in all repair techniques (P < .01). A 2-fold increase occurred in load to failure of the 2 common anchor types (143 +/- 8 and 165 +/- 20 N). The load to failure for the transosseous repair (86 +/- 8 N) increased 1.7-fold. The addition of an adhesive to the tendon-bone-suture interface significantly enhances ultimate load and total energy required to failure in 3 types of rotator cuff repair. The unique properties of this frog glue (strong, flexible and sets in water) may ultimately lead to its use as an adjunct to rotator cuff repair in humans. LEVEL OF EVIDENCE: Basic science study.

Addition of nitric oxide through nitric oxide-paracetamol enhances healing rat achilles tendon.

Nitric oxide is an important messenger molecule in many physiological processes. The addition of NO via NO-flurbiprofen enhances the material properties of healing tendon, however, flurbiprofen has a detrimental effect on healing. We asked if NO delivered by a cyclooxygenase 3 inhibitor (paracetamol/acetaminophen) would enhance healing in a rat Achilles tendon healing model. Rats were injected subcutaneously daily with NO-paracetamol, paracetamol or vehicle from two days before surgery to the day of tissue harvesting. Paracetamol had no effect on tendon healing compared with vehicle alone. NO-paracetamol did not change the failure load, but did decrease the water content, enhance the collagen content, reduce the cross-sectional area and improve the ultimate stress of healing tendon compared with paracetamol and vehicle. The collagen organization of the healing tendon in the NO-paracetamol group, as determined by polarized light microscopy, was enhanced. Our data suggests NO-paracetamol increases the total collagen content and enhances organization while decreasing the cross-sectional area of healing rat Achilles tendon and is consistent with human clinical trials where NO has improved the symptoms and signs of tendinopathy.

Aggrecan, versican and type VI collagen are components of annular translamellar crossbridges in the intervertebral disc.

The aim of this study was to undertake a detailed analysis of the structure of the inter and intra-lamellar regions of the annulus fibrosus. A total of 30 newborn to 6 year-old lumbar ovine intervertebral discs (IVDs) were fixed and decalcified en-bloc to avoid differential swelling artifacts during processing and vertical mid-sagittal, and horizontal 4 mum sections were cut. These were stained with toluidine blue to visualise anionic proteoglycan (PG) species, H & E for cellular morphology and picro-sirius red (viewed under polarized light) to examine collagenous organization. Immunolocalisations were also undertaken using anti-PG core-protein and glycosaminoglycan (GAG) side chain antibodies to native chondroitin sulphate (CS), Delta C-4-S and C-6-S unsaturated stubs generated by chondroitinase ABC digestion of CS, keratan sulphate (KS), and with antibodies to type I, II, VI, IX and X collagens. Trans-lamellar cross bridges (TLCBs), discontinuities in annular lamellae's which provide transverse interconnections, stained prominently with toluidine blue in the adult IVDs but less so in the newborn IVDs. In adult discs TLCBs were evident in both the posterior and anterior AF where they extended from the outermost annular lamellae almost to the transitional zone extending across as many as eight lamellar layers displaying a characteristic circuitous, meandering, serpentine type course. There were significantly fewer TLCBs in 2 week-old compared with skeletally mature sheep and there was a further increase from 2 to 6 years. Immunolocalisation of perlecan delineated blood vessels in the TLBs of the newborn but not adult IVDs extending into the mid AF. In contrast adult but not 2 week-old TLCBs were immunopositive for C-4-S, C-6-S, KS, aggrecan, versican and type VI collagen. The change in number and matrix components of the trans-lamellar cross bridges with skeletal maturity and ageing suggest that they represent an adaptation to the complex biomechanical forces occurring in the annulus fibrosus.

Immature sheep spines are more flexible than mature spines: an in vitro biomechanical study.

STUDY DESIGN: Dynamic triaxial biomechanical testing of immature and mature ovine spine motion segments. OBJECTIVE: To compare torque-deflection parameters of mature and immature spine motion segments and to investigate whether scaling relationships apply between mature and immature motion segment torque-deflection responses. SUMMARY OF BACKGROUND DATA: While previous studies have examined the cervical region in a limited number of loading directions, a comprehensive multiaxial study of the response of the pediatric spine at all 3 spinal levels (cervical, thoracic, and lumbar) has not been performed. METHODS: Motion segments from cervical, thoracic, and lumbar levels were tested under moment application about 3 axes for newborn and 2-year-old sheep. Range of motion, neutral zone, and stiffness were calculated for each motion segment and compared for immature and mature spine. RESULTS: Immature spine motion segments exhibited a significantly larger range of motion (P < 0.001) and neutral zone (P < 0.001) and significantly lower stiffness (P < 0.001) in comparison to mature spine segments about the 3 moment axes, at the 3 spinal levels tested. There were statistically significant interactions between specimen age and the moment axis and/or spinal level for some torque-deflection parameters. CONCLUSION: The significantly greater neutral zone of immature spine suggests greater ligament laxity. Significantly higher range of motion and lower stiffness of the immature spine may be implicated in spinal cord injury mechanisms and implies a change in relative tolerance of the spine to damage with spinal maturity. Significant statistical interactions between spinal maturity and moment axis or motion segment level suggest that scaling torque-deflection parameters from mature to immature spine may not be appropriate.

Dynamic biomechanics correlate with histopathology in human tibial cartilage: a preliminary study.

Improved staging of cartilage degeneration is required, particularly during early stages when minimal surface damage is visible arthroscopically. Degradation of articular cartilage extracellular matrix, resulting from degenerative changes associated with osteoarthritis, can influence its functional properties. Cartilage mechanical properties therefore may provide a quantitative method for monitoring degenerative change in this tissue. We determined whether dynamic mechanical properties of cartilage (effective shear modulus and phase lag) measured with a handheld indenter correlated with histopathology scores, proteoglycan, and collagen content or expression of chondrocyte-specific (aggrecan, collagen II) or dedifferentiation (collagen I and III) genes in human osteoarthritic cartilage with International Cartilage Repair Society scores of 0 to 1. We observed an association between the histopathologic stage of cartilage disease and dynamic shear modulus and phase lag. In contrast, there generally was a poor relationship between cartilage biomechanical properties and biochemistry with the only noteworthy correlation being between shear modulus and collagen. Phase lag but not shear modulus correlated with gene expression. These data support the potential of dynamic indentation for assessing the stage of cartilage degeneration in tissue with minimal gross surface damage.

Rotator cuff repair: an ex vivo analysis of suture anchor repair techniques on initial load to failure.

PURPOSE: To determine the best combination of anchors and suture techniques for repairing torn rotator cuff tendons. TYPE OF STUDY: Ex vivo biomechanical investigation. METHODS: Sixty fresh-frozen sheep infraspinatus tendons were repaired using 6 different repair techniques: transosseous sutures with 2 sutures and mattress stitches; 2 suture anchors with 1 suture per anchor using either simple stitches, mattress stitches, or modified Kessler stitches; 2 suture anchors with 2 sutures per anchor using simple stitches; or 5 suture anchors with 1 suture per anchor and a mattress stitch pattern. RESULTS: No difference was identified between transosseous sutures (mean +/- SD, 147 +/- 68 N) and suture anchors (140 +/- 36 N) when 2 mattress stitches were used. The weakest construct with suture anchors was when the tendon was grasped with 2 suture anchors with 1 suture per anchor and a simple stitch pattern (72 +/- 25 N). Repair strength increased 2-fold with 2 suture anchors single loaded and a mattress stitch configuration (140 +/- 36 N; P = .026), 3-fold with 2 suture anchors single loaded and a modified Kessler stitch pattern (204 +/- 32 N; P < .001), and 3-fold with 2 suture anchors double loaded and a simple stitch suture pattern (212 +/- 39 N; P < .001). The highest tensile load was observed with 5 suture anchors in a double-row configuration, single loaded, that grasped the tendon with mattress stitches (336 +/- 59 N; P < .001). CONCLUSIONS: This study shows that in an ovine model, initial rotator cuff repair strength can be enhanced by increasing the number of suture anchors used in the repair and by using anchors that are double loaded with suture and suture configurations that pass more frequently through the tendon. CLINICAL RELEVANCE: The clinical relevance of this ex vivo investigation is that the initial load to failure of a rotator cuff repair may be increased by increasing the number of suture anchors, the number of sutures per anchor, or using suture patterns that grab more adjacent tendon fibers.

Deletion of iNOS gene impairs mouse fracture healing.

Nitric oxide (NO) is a signaling molecule synthesized from l-arginine by nitric oxide synthases (NOSs). NOS isoforms are either constitutive (endothelial NOS [eNOS] and neuronal NOS [nNOS]) or inducible NOS (iNOS). Previously, our group has reported that NO is expressed during and modulates fracture healing. In this study, we evaluated the specific contribution of iNOS to fracture healing by using iNOS gene therapy in iNOS-deficient mice. Twelve-week-old female wild-type mice and iNOS-KO mice had a right femoral midshaft osteotomy fixed with an intramedullary 0.5-mm-diameter needle. A gelatine sponge was implanted across the fracture site. The gelatine sponge received either Ad5-CMViNOS (in iNOS-deficient mice; n=16) or Ad5-CMVempty (in wild-type mice; n=15, and iNOS-deficient mice; n=15) at a dose of 10(7) pfu. Mice were sacrificed at day 14, and their right and left hind limbs were harvested. Cross-sectional area (CSA) was determined by measuring the callus diameter across the mediolateral and anteroposterior plane using a vernier caliper. Specimens were loaded to failure torsionally in a biaxial INSTRON testing system, and maximum torque, torsional stiffness, and maximal and total energy were determined. Deletion of the iNOS gene decreased the total and maximum energy absorption of the healing femoral fracture by 30% and by 70% (P<0.01), respectively, in comparison to the wild-type mice. This reduction in energy absorption was reversed by iNOScDNA administration via adenovirus vector. Furthermore, iNOScDNA caused an increase in torsional failure by 20% (P=0.01) in comparison to iNOS(-/-) mice that did not receive the iNOScDNA. There were no significant differences in the biomechanical properties of intact femora. These data indicate that iNOS is important in mouse fracture healing. However, the clinical utility of NOS gene therapy to enhance fracture healing will need further evaluation.

Topical glyceryl trinitrate application in the treatment of chronic supraspinatus tendinopathy: a randomized, double-blinded, placebo-controlled clinical trial.

BACKGROUND: Topical glyceryl trinitrate therapy has previously demonstrated short-term pain reduction in patients with supraspinatus tendinopathy. HYPOTHESIS: Topical glyceryl trinitrate improves outcome measures in patients with supraspinatus tendinopathy. STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1. METHODS: Fifty-three patients (57 shoulders) were recruited, and the authors completed a prospective, randomized, double-blinded, placebo-controlled clinical trial of continuous topical glyceryl trinitrate treatment (1.25 mg/24-h glyceryl trinitrate). RESULTS: The glyceryl trinitrate group had significantly reduced shoulder pain with activity, at night, and at rest at week 24 (P = .03); reduced internal rotation impingement at week 24 (P = .02); increased range of motion in abduction and internal rotation at week 24 (P = .04); and increased force at weeks 12 and 24 with supraspinatus muscle testing (P = .001), external rotation (P = .04), internal rotation (P = .01), adduction (P = .04), and subscapularis pushoff (P = .01). Forty-six percent of patients on glyceryl trinitrate patches were asymptomatic with activities of daily living at 6 months compared with 24% of patients with tendon rehabilitation alone (P = .007, chi(2) analysis). Mean effect size for all outcome measures was 0.26. DISCUSSION: Topical glyceryl trinitrate treatment significantly improved pain scores, range of motion, internal rotation impingement, muscular force, and patient outcomes in patients with supraspinatus tendinopathy. Topical glyceryl trinitrate should be included as part of nonsurgical management of chronic tendinopathies.

The nitric oxide donor glyceryl trinitrate increases subchondral bone sclerosis and cartilage degeneration following ovine meniscectomy.

AIM: To examine the effect of glyceryl trinitrate (GTN), a nitric oxide (NO) donor compound, on the concurrent progression of cartilage and subchondral bone changes in an ovine meniscectomy model of osteoarthritis (OA). METHODS: Bilateral lateral meniscectomy (MX) was performed on 12 ewes to induce OA. Six were treated with topical GTN (0.7mg/kg twice weekly) (MX+GTN). Six other sheep formed non-operated controls (NOC). After sacrifice at six months, the subchondral bone density (BMD) of the lateral and medial femoral condyles (LFC, MFC) and tibial plateau (LTP, MTP) was assessed by DEXA. Dynamic biomechanical testing was performed across the MTP and LTP. Histological sections from each region were scored qualitatively and the thickness of the subchondral bone plate (SCB) was determined by image analysis. RESULTS: MX+GTN displayed significantly greater SCB thickness relative to MX in the LFC (mean increase +88% and +42%, respectively) and the MFC. SCB BMD was 10-12% greater in MX+GTN relative to MX in the LFC, LTP and MTP. MX+GTN sheep also showed greater increases in some histopathology variables, greater central erosion of the LTP, and changes in dynamic stiffness (decreased) and phase lag (increased) in the outer zone of the LTP. CONCLUSIONS: Treatment with GTN significantly increased subchondral bone thickness and density during subchondral remodelling following meniscectomy. In addition, it slightly but significantly worsened degeneration of cartilage structure and function. These results suggest that clinical use of GTN may accelerate both cartilage degeneration and subchondral bone sclerosis if used in the presence of OA, and demonstrate that NO has the potential be an important mediator of the subchondral bone changes seen in OA.

Topical glyceryl trinitrate treatment of chronic noninsertional achilles tendinopathy. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Noninsertional Achilles tendinopathy is a degenerative overuse disorder. No method has been universally successful in treating this condition. Topically applied nitric oxide has been shown, in animal models, to be effective for the treatment of fractures and cutaneous wounds through mechanisms that may include stimulation of collagen synthesis in fibroblasts. The goal of the present study was to determine if topical glyceryl trinitrate improves clinical outcome measures in patients with Achilles tendinopathy. METHODS: A prospective, randomized, double-blind, placebo-controlled trial involving a total of sixty-five patients (eighty-four Achilles tendons) was performed to compare continuous application of topical glyceryl trinitrate (at a dosage of 1.25 mg per twenty-four hours) with rehabilitation alone for the treatment of noninsertional Achilles tendinopathy. RESULTS: Compared with the control group, the glyceryl trinitrate group showed reduced pain with activity at twelve weeks (p = 0.02) and twenty-four weeks (p = 0.03), reduced night pain at twelve weeks (p = 0.04), reduced tenderness at twelve weeks (p = 0.02), decreased pain scores after the hop test at twenty-four weeks (p = 0.005), and increased ankle plantar flexor mean total work compared with the baseline level at twenty-four weeks (p = 0.04). Twenty-eight (78%) of thirty-six tendons in the glyceryl trinitrate group were asymptomatic with activities of daily living at six months, compared with twenty (49%) of forty-one tendons in the placebo group (p = 0.001, chi-square analysis). The mean effect size for all outcome measures was 0.14. CONCLUSIONS: Topical glyceryl trinitrate significantly reduced pain with activity and at night, improved functional measures, and improved outcomes in patients with Achilles tendinopathy.

Accuracy and reliability of a dynamic biomechanical skin measurement probe for the analysis of stiffness and viscoelasticity.

A novel instrument has been devised for the in vivo examination of the dynamic biomechanical properties of skin. These properties include stiffness and viscoelasticity. The advantage of the device is its ability to examine the skin dynamically, thereby eliminating preconditioning effects. Furthermore, it is portable, hand-held and easy to operate in the clinical environment. The objective of this study was to determine the accuracy and reliability of the dynamic biomechanical skin measurement (DBSM) probe. The accuracy was determined by examining a series of silicone elastomer specimens. A comparison of the shear modulus (G*), obtained from a static indentation system, with stiffness, obtained from the DBSM probe, was performed. The reliability was determined by examining both silicone elastomers and forearm volar skin in vivo. In both cases assessment was by six different operators (inter-reliability) and also by an individual operator (intra-reliability). Statistical analysis was performed using Levene's test of homogeneity and analysis of variance to ascertain if there were significant differences between operators (inter-reliability) and with one individual operator (intra-reliability). It can be concluded, from this study, that the DBSM probe is accurate (R2 = 0.96, p = 0.01). It is also inter- and intra-reliable when assessing elastomer stiffness and skin stiffness. However, phase lag was not found to be a useful indicator of device reliability. It is anticipated that this device will be used to examine dermatological conditions and the benefits, or otherwise, of treatment. The DBSM probe promises to contribute to the objective measurement of physical properties of the skin in future investigative studies.

The Orthopaedic Research Institute-Tennis Elbow Testing System: A modified chair pick-up test-interrater and intrarater reliability testing and validity for monitoring lateral epicondylosis.

Lateral epicondylosis is a degenerative overuse tendinopathy involving the extensor tendons of the forearm, predominantly the extensor carpi radialis brevis, in the region of the lateral epicondyle of the elbow. The Orthopaedic Research Institute-Tennis Elbow Testing System (ORI-TETS) is designed to record objective measurements of force generated with a simulated chair pick-up test. Interrater reliability of the ORI-TETS was excellent, with high intraclass correlation coefficients (ICCs) for right arm mean peak force of 0.93, left arm mean peak force of 0.84, right arm mean total force of 0.93, and left arm mean total force of 0.86. The ORI-TETS also demonstrated excellent intrarater reliability, with ICCs ranging from 0.9 to 0.97. The relative technical error of the ORI-TETS for all measurements ranged from 5.8% to 7.2%. Testing patients with lateral epicondylosis (N = 16) and comparing analog pain scores with ORI-TETS testing demonstrated a strong negative relationship between the two parameters (Spearman rho, -0.87 to -1.0). Thus, the ORI-TETS is a reliable and reproducible testing system for the forearm extensors. The testing system is inexpensive, takes 5 minutes to perform, and demonstrates good predictive value for objectively assessing patients with lateral epicondylosis. This system could be used for routine clinical monitoring of patients with lateral epicondylosis.

Topical nitric oxide application in the treatment of chronic extensor tendinosis at the elbow: a randomized, double-blinded, placebo-controlled clinical trial.

BACKGROUND: Extensor tendinosis ("tennis elbow") is a degenerative overuse tendinopathy of the wrist extensors at their attachment to the lateral humeral epicondyle. No treatment has been universally successful. Topical application of nitric oxide has been used effectively to treat fractures and cutaneous wounds in animal models, presumably by stimulation of collagen synthesis in fibroblasts. PURPOSE: To determine whether topical nitric oxide can improve outcome of patients with extensor tendinosis. STUDY DESIGN: Prospective, randomized, double-blinded clinical trial. METHODS: Eighty-six patients with extensor tendinosis were randomized into two equal groups; both were instructed to perform a standard tendon rehabilitation program. One group received an active glyceryl trinitrate transdermal patch, and the other group received a placebo patch. RESULTS: Patients in the glyceryl trinitrate group had significantly reduced elbow pain with activity at 2 weeks, reduced epicondylar tenderness at 6 and 12 weeks, and an increase in wrist extensor mean peak force and total work at 24 weeks. At 6 months, 81% of treated patients were asymptomatic during activities of daily living, compared with 60% of patients who had tendon rehabilitation alone. CONCLUSIONS: Application of topical nitric oxide improved early pain with activity, late functional measures, and outcomes of patients with extensor tendinosis.

Meniscal and chondral loss in the anterior cruciate ligament injured knee.

Rupture of the anterior cruciate ligament (ACL) of the knee is a commonly occurring injury in the athletic population. Associated meniscal and chondral injury is well recognised. This occurs both at the time of index injury and also secondarily over time in the ACL-deficient knee as a result of several related pathways culminating in osteoarthritis. ACL reconstruction is a well established surgical technique for treatment of symptomatic instability in ACL-deficient knees but the role of ACL reconstruction in the prevention of osteoarthritis remains unclear. This article reviews the contemporary literature on the pathophysiology of chondral and meniscal loss in ACL-injured knees and the role of current treatment techniques, including surgical reconstruction of ligamentous, meniscal and chondral pathology, in altering the natural history of the ACL-deficient knee.

Rotator cuff repair with bioabsorbable screws: An in vivo and ex vivo investigation.

PURPOSE: The purpose of this study was to evaluate in vivo the clinical outcomes of rotator cuff repairs with bioabsorbable screws compared with metal suture anchors, and to compare the ex vivo initial load to failure of rotator cuff repairs using 3 different bioabsorbable screws, suture anchors, and transosseous sutures. TYPE OF STUDY: In vivo clinical outcomes investigation, and ex vivo biomechanical study. METHODS: Three cohorts of patients with rotator cuff tears that measured less than 4 cm(2), were sequentially repaired with Mitek Rotator Cuff QuickAnchors (Mitek Surgical Products, Norwood, MA) (n = 9), Arthrex Headed Bio-Corkscrews (n = 9) (Arthrex, Naples, FL), and Mitek Rotator Cuff QuickAnchors (n = 9). Patients were systematically assessed with a specific shoulder questionnaire and 23 shoulder tests performed preoperatively and at 1 and 6 weeks, 3 and 6 months, and 1 year postoperatively. A correlative ex vivo biomechanical study was performed on 53 ovine shoulders to evaluate the initial failure load properties of bioabsorbable screws compared with fixation with suture anchors and transosseous sutures. RESULTS: In the in vivo portion of the study, the cohort treated with the Headed Bio-Corkscrew demonstrated no improvement on any measured parameter until 1-year after rotator cuff repair. In contrast, shoulders repaired with Mitek Rotator Cuff QuickAnchors demonstrated improved overall shoulder function as early as 6 weeks postoperatively (P =.002), had a better constant score at 1-year after repair (88 +/- 9 v 73 +/- 17; P =.016), and a lower rate of revision rotator cuff repair (P =.029). In the ex vivo portion of the study, the bioabsorbable headed screws, Headed Bio-Corkscrew (100 +/- 30 N) and BioTwist (76 +/- 35 N), had inferior initial failure load properties compared with suture anchors (140 +/- 36 N) and transosseous sutures (147 +/- 68 N). In contrast, the BioCuff (190 +/- 56 N), a bioabsorbable implant that used a screw and serrated washer design, had equivalent initial failure load properties as the suture repairs. CONCLUSIONS: This investigation had poorer early outcomes, a lower shoulder functional score 1-year after repair, and a higher rate of repeat surgery in patients who had their rotator cuff repaired with a bioabsorbable screw than in patients who had their shoulders repaired with a standard metal suture anchor. Furthermore, the biomechanical testing demonstrated a lower tensile load to failure in the tendons repaired with a simple screw design compared to suture anchors with a mattress stitch. Of note, the implant that used a screw and washer design demonstrated a greater ability to resist initial tensile load.