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Biomedical subjects

George A C Murrell

Publications and source records attributed to George A C Murrell.

At least 19 recordsLinked to original sources

Oxidative stress-induced c-Jun N-terminal kinase (JNK) activation in tendon cells upregulates MMP1 mRNA and protein expression.

To explore the potential mechanisms of tendon degeneration, we investigated the role of c-Jun N-terminal Kinase (JNK) activation and the regulation of matrix metalloproteinase 1 (MMP1) in tendon matrix degradation under oxidative stress. JNK and MMP1 activity in samples from normal and ruptured human supraspinatus tendons was evaluated by immunohistochemistry. Real-time quantitative PCR was utilized to evaluate MMP1 mRNA expression and Western blotting for MMP1 and JNK protein detection. JNK activation and increased MMP1 activity were found in the torn human supraspinatus tendon tissue, as well as in human tendon cells under in vitro oxidative stress. Inhibition of JNK prevented MMP1 overexpression in oxidative stressed human tendon cells. Results from the current study indicated that stress activated JNK plays an important role in tendon matrix degradation, possibly through upregulating of MMP1.

Humans↗

The rotator cuff functional index.

BACKGROUND: Despite improvements in the clinical assessment of rotator cuff injuries, shortcomings exist in diagnosing rotator cuff tears. PURPOSE: To formulate a clinical rotator cuff functional index for predicting rotator cuff tears based on handheld dynamometer measurements for shoulder strength testing and to assess its ability to diagnose a rotator cuff tear. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Preoperative handheld dynamometer measurements, including supraspinatus, external rotation, internal rotation, adduction, and lift-off force, were compared in 100 patients with full-thickness rotator cuff tears (> 1.0 cm) and 100 patients with no rotator cuff injury (confirmed by arthroscopy). Using multiple logistic regression analysis, the rotator cuff functional index and index for rotator cuff tear size were formulated in which 100 represented excellent rotator cuff function and less than 0 indicated a full-thickness supraspinatus tear. Each patient's index was calculated to determine its clinical value in predicting a rotator cuff tear; the Pearson correlation coefficient was established for the rotator cuff functional index for rotator cuff size. RESULTS: Two handheld dynamometer measurements predicted a rotator cuff tear (P < .001, r = 0.53), with rotator cuff functional index = 1.27 * supraspinatus (N) - 0.72 * adduction (N) - 11.6, but not tear size (r = 0.38). In predicting a rotator cuff tear (rotator cuff functional index < 0 = rotator cuff tear; rotator cuff functional index > 0 = no tear), the rotator cuff functional index had 83% sensitivity, 79% specificity, 80% positive predictive value, 82% negative predictive value, likelihood ratio of 4.0 for a positive test result and 0.2 for a negative test result and an accuracy of 81%. CONCLUSION: The 2 most useful tests for determining a rotator cuff tear with a handheld dynamometer were supraspinatus force and adduction force (as negative control). A functional index based on these measurements was able to rule out a rotator cuff tear and predict the presence but not the size of the tear.

Adult↗

Nitric oxide enhances collagen synthesis in cultured human tendon cells.

Collagen deposition is an important process that occurs during wound healing. We and others have shown that nitric oxide (NO) is important in tendon healing. The mechanisms whereby healing is enhanced are, however, undetermined. The aim of this study was to investigate whether NO could enhance collagen synthesis in cultured human tendon cells via exogenous NO and via an adenovirus containing the gene for inducible nitric oxide synthase (Ad-iNOS). Tendon cells from the torn edge of the tendons of patients undergoing rotator cuff repair surgery were cultured following collagenase digestion, and stimulated with exogenous NO (SNAP), transfected with Ad-iNOS, and treated with the NOS inhibitor, L-NMMA. Total protein and collagen synthesis were evaluated by (3)H-proline and collagenase sensitive (3)H-proline incorporation in human tendon cells. High doses of exogenous NO (SNAP) inhibited collagen synthesis. Lower doses enhanced total protein and collagen synthesis of the tendon cells. Ad-iNOS successfully transfected active iNOS into human tendon cells in vitro and also enhanced total protein and collagen synthesis of the tendon cells. The NOS inhibitor, L-NMMA, inhibited the effects of iNOS on the cells. Our studies show for first time that nitric oxide can enhance collagen synthesis in human tendon cells in vitro. These results may explain, in part, at least, the beneficial effects of NO donors in animal models and during the treatment of tendonopathies in human clinical trials. .

Adenoviridae↗

Gene expression changes in SNAP-stimulated and iNOS-transfected tenocytes--expression of extracellular matrix genes and its implications for tendon-healing.

Nitric oxide (NO) has a variety of physiological roles, including acting as a key mediator in various phases of tendon healing, but its importance as a modulator of gene expression during tendon healing has not been well studied. The current study used microarray analysis to elucidate global gene expression after transfection with inducible nitric oxide synthase (iNOS) in tenocytes isolated from the injured rotator cuff tendons of human patients. We show that the expression of a wide range of genes is affected by NO, with many activated genes having known roles in healing. Of particular significance is that NOS overexpression stimulates the transcription and translation of a range of extracellular matrix genes important to the structure of connective tissues such as tendons, including collagen Ialpha1, collagen IIIalpha1, collagen IValpha5, biglycan, decorin, laminin, and matrix metalloproteinase 10 (MMP10). These genes were also shown to respond to stimulation by the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) in a dose-dependent manner. We further show that varying levels of NO significantly affect cellular adhesion in tenocytes, a critical process during tendon repair. These findings will be of use when optimizing the dose of NO delivery in further work investigating NO as potential treatment of tendon injuries.

Aged↗

Arthroscopic stabilization of superior labral (SLAP) tears with biodegradable tack: outcomes to 2 years.

PURPOSE: This prospective study aimed to document the pain and functional outcomes, over time, of patients whose SLAP lesions had been repaired with biodegradable tacks. METHODS: Superior labral tears were identified in 24 patients from a cohort of 500 patients who had shoulder problems sufficiently disabling to warrant arthroscopic evaluation and management. These labral tears were arthroscopically repaired with 1 to 3 biodegradable tacks (mean, 1.6). Before surgery, all patients completed a questionnaire regarding their shoulder pain and function and were given a systematic clinical examination. To observe their postoperative outcomes over time, the same assessments were made at 2 weeks, 6 weeks, 3 months, 6 months, 1 year, and 2 years after surgery. RESULTS: After labral reattachment, decreases were noted in the patients' mean shoulder pain scores at rest (64% at 3 months), at night (76% at 3 months), and with activity (73% at 6 months). The most significant reductions in mean scores occurred between 6 and 12 weeks (P < .001). Patient-perceived weakness, instability, and stiffness scores also improved from week 6. The ranking of the patients' "overall problem" reduced from an average ranking of "severe" to "mild" by the third preoperative month (P < .001) and was still at this level by the time of their 2-year follow-up appointment. Activity levels for 22 of 24 patients returned to their preinjury levels by 6 months after surgery. CONCLUSIONS: Arthroscopically delivered biodegradable tacks effectively managed superior labral tears and, on average, resulted in a near-complete improvement of pain and recovery of function by 3 months. These good outcomes did not improve further or deteriorate at the 2-year follow-up appointment. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Absorbable Implants↗

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.

Administration, Topical↗

Early inflammatory reaction after rotator cuff repair with a porcine small intestine submucosal implant: a report of 4 cases.

BACKGROUND: Porcine small intestine submucosal grafts have been successful in enhancing soft tissue repair, as demonstrated by animal studies. Currently, there are no reports of the use of such implants in human rotator cuff repair. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Over a 6-month period, 25 patients underwent rotator cuff repair by one surgeon using the Restore Orthobiologic Implant to augment the repaired tendon or fill a defect. RESULTS: Four of 25 patients experienced an overt inflammatory reaction at a mean of 13 days postoperatively. All patients underwent open irrigation and debridement of the rotator cuff and porcine small intestine submucosal implant. CONCLUSION: Porcine small intestine submucosal implants should be used in rotator cuff surgery with the awareness that a non-specific inflammatory reaction can occur in the early postoperative period. This inflammatory reaction may cause breakdown of the repair. Further studies are needed to further characterize the reaction and determine which patients are susceptible.

Aged↗

The effects of thermal capsular shrinkage on the outcomes of arthroscopic stabilization for primary anterior shoulder instability.

BACKGROUND: The effectiveness of arthroscopic thermal capsulorrhaphy in the prevention of recurrent instability in primary anterior stabilization is undetermined. PURPOSE: To determine if patients with recurrent anterior shoulder instability who have labral repair plus arthroscopic thermal capsulorrhaphy have better outcomes than those with labral repair alone. STUDY DESIGN: Cohort study; Level of evidence, 3. METHOD: There were 72 patients who underwent arthroscopic anterior shoulder stabilization with Suretac II tacks (n = 32) during 1996 to 1999 or with Suretac II tacks plus arthroscopic radiofrequency capsular shrinkage (n = 40) from 1999 to 2002. Standardized patient-determined and examiner-determined outcome measures were obtained preoperatively and at 3, 6, 12, and 24 months postoperatively. Statistical analyses included a Kaplan-Meier analysis of time to recurrent instability. RESULTS: Of the 72 patients, 66 had complete follow-up, including 28 patients treated with the Suretac stabilization and 38 patients with the Suretac plus radiofrequency shrinkage, for a mean follow-up of 58 and 30 months, respectively. All patients had a Bankart lesion. Both groups had similar results with respect to patient-determined and examiner-determined outcome measures. The only adverse outcome was postoperative recurrent instability in 6 of 28 cases in the Suretac group alone and 8 of 38 cases in the Suretac-plus -shrinkage group. Most recurrent instability occurred between 6 and 24 months. Kaplan-Meier analysis for time to recurrent instability showed no differences in the rate of instability recurrence between the 2 groups. CONCLUSION: Arthroscopic thermal capsulorrhaphy neither enhanced nor impaired the outcomes of arthroscopic labral repair with biodegradable tacks in patients with primary recurrent anterior shoulder instability.

Adult↗

An evaluation of the effects of the extent of capsular release and of postoperative therapy on the temporal outcomes of adhesive capsulitis.

PURPOSE: To evaluate effects of the extent of surgical release and of postoperative physiotherapy on the outcomes of this procedure. TYPE OF STUDY: Case-controlled cohort study. METHODS: Pain and range of motion scores were compared preoperatively, operatively, and at 1, 6, 12, 24, 52, and 104 weeks postoperatively, in 2 temporal cohorts of patients with adhesive capsulitis. The first cohort (n = 18) underwent a 155 degrees +/- 40 degrees (mean +/- SEM) standard anteroinferior arthroscopic capsule release of the shoulder (ACR-S) and rehabilitation. The second cohort (n = 22) underwent capsular release that was extended an additional 65 degrees +/- 65 degrees posteriorly, a portion of the intra-articular part of the subscapularis tendon was divided, and the patients had a modified earlier, supervised postoperative physical therapy program (ACR-M). RESULTS: In both cohorts, there was a significant reduction in pain 1 week after surgery, which was maintained at all time-points (P < .05). More gains in intraoperative range of forward flexion (121 degrees v 150 degrees), abduction (114 degrees v 146 degrees) and external rotation (55 degrees v 68 degrees) were obtained in the ACR-M cohort (P < .001). Six weeks after surgery, external and internal rotation regressed to preoperative levels in the ACR-S cohort; 2 of them required a re-release. This regression was not observed in the ACR-M cohort. There was no instability or weakness in lift-off power in either cohort. CONCLUSIONS: This is a level IV study of 2 nonrandomized cohorts where simultaneous changes in surgical technique and rehabilitation were introduced to the ACR-M cohort. Arthroscopic capsular release for adhesive capsulitis resulted in significant reductions in pain by 1 week in both cohorts. A more extensive capsular release with division of the intra-articular portion of subscapularis improved intraoperative motion. Gains in internal and external rotation were lost postoperatively in the ACR-S cohort, but were preserved when an extended surgical release and an early, supervised postoperative physical therapy program was initiated in the ACR-M cohort. LEVEL OF EVIDENCE: Level IV.

Adult↗

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.

Animals↗

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.

Animals↗

Prevention of shoulder stiffness after rotator cuff repair.

UNLABELLED: Predisposing factors for shoulder stiffness after rotator cuff repair have yet to be determined. The potential for recovery of range of motion and amelioration of pain in patients with this complication also remains unclear. Accordingly, data collected prospectively for 209 patients with a primary rotator cuff repair were retrospectively reviewed. Two groups, Group A (early motion recovery) and Group B (shoulder stiffness), were selected according to passive shoulder range of motion outcomes 6 weeks postoperatively. Both groups were compared for 10 descriptive and clinical characteristics, and for passive range of motion, muscle force, and functional outcomes obtained 0, 6, 12, 24, and 76 weeks postoperatively. Of the potential prognostic factors examined, restriction of range of motion for the preoperative hand behind the back best predicted shoulder stiffness at 6 weeks postoperatively. For patients with postoperative shoulder stiffness, pain had subsided by 24 weeks postoperatively, whereas range of motion steadily improved between 6 weeks and 76 weeks postoperatively. Results of the current study support a predictive role for restriction of range of motion for the preoperative hand behind the back, and affirms the potential for nearly complete recovery of range of motion and amelioration of pain in patients who have shoulder stiffness after rotator cuff repair. LEVEL OF EVIDENCE: Prognostic study, Level I-1 (prospective study).

Adult↗

Overexpression of antioxidant enzyme peroxiredoxin 5 protects human tendon cells against apoptosis and loss of cellular function during oxidative stress.

Oxidative stress and apoptosis are implicated in tendon degeneration. Peroxiredoxin 5 (PRDX5) is a novel thioredoxin peroxidase recently identified in mammals, participating directly in eliminating hydrogen peroxide (H(2)O(2)) and neutralizing other reactive oxygen species (ROS). We have previously reported that PRDX5 is upregulated in degenerative human tendon. However, the effects of this upregulation on human tendon cell function remain unknown, in particular, with regards to oxidative stress conditions. Here we report that exposure of human tendon cells to 50 microM H(2)O(2) for 24 h (in vitro oxidative stress) caused a significant increase in the percentage of apoptotic cells (P<0.05) as assessed by flow cytometric analysis of Annexin V binding, accompanied by increased PRXD5 mRNA and protein expression. Overexpression of PRDX5 in human tendon cells via transfection inhibited H(2)O(2)-induced tendon cell apoptosis by 46% (P<0.05), and prevented the decrease in tendon cell collagen synthesis which occurs under H(2)O(2) challenge, although the decrease in collagen synthesis was small. Results from our study indicate that the antioxidant enzyme PRDX5 plays a protective role in human tendon cells against oxidative stress by reducing apoptosis and maintaining collagen synthesis.

Annexin A5↗

A randomised clinical trial evaluating the efficacy of physiotherapy after rotator cuff repair.

The optimal form of rehabilitation after rotator cuff repair has yet to be determined. A randomised clinical trial was undertaken to compare outcomes for two forms of rehabilitation for this condition: individualised supervised physiotherapy treatment, and a standardised unsupervised home exercise regime. Fifty-eight volunteers with all sizes of operatively repaired rotator cuff tears were allocated randomly to one of the two treatment groups. All subjects received a standardised home exercise regime. Subjects who were randomised to the physiotherapy group received additional individualised treatment. Independent, blinded assessments of range of motion, muscle force and functional outcome measures were performed pre-operatively, and at six, 12 and 24 weeks postoperation. At six, 12 and 24 weeks post-operation, comparable outcomes were demonstrated for both rehabilitation groups. By 24 weeks post-operation, most subjects demonstrated outcomes that were consistent with a favourable recovery, regardless of rehabilitation mode. On the basis of these results, outcomes for subjects allocated to individualised physiotherapy treatment after rotator cuff repair are no better than for subjects allocated to a standardised home exercise regime.

Adult↗

Identification of prognostic indicators for patient outcomes in extensor tendinopathy at the elbow.

Extensor tendinopathy is a degenerative overuse condition involving the common extensor tendon at the lateral humeral epicondyle. The diagnosis and management of this condition are clinically based. Our aims were to determine if through patient history and clinical examination we could ascertain prognostic factors affecting time to symptom resolution in extensor tendinopathy. Symptomatic patients (N=28) had a thorough history and examination, and rehabilitation monitored regularly for 6 months. Patient outcomes at 6 months were then correlated with specific factors on initial presentation. Factors implicated as having prognostic significance regarding patient outcomes were a current history of manual work (P=0.04, effect size -0.29), and a current history of weekly participation in racquet sports (P=0.01, effect size -0.41). These individual factors had a significantly decreased chance of symptom resolution at the 6-month stage, and when combined had an effect size of -0.6 (P=0.001). Negative patient outcomes may be related to current high and repetitive levels of tendon stress, and rest from recreational and occupational use of wrist extensor tendons may be necessary to enhance the chances of complete symptom resolution. Enforced rest has monetary and quality-of-life implications, but is probably preferable to an incomplete recovery and prolonged tendon pain and dysfunction.

Adult↗

Diagnostic values of tests for acromioclavicular joint pain.

BACKGROUND: This prospective study was performed to determine which clinical and imaging tests were most helpful for diagnosing acromioclavicular joint pain. METHODS: Of 1037 patients with shoulder pain, 113 who mapped pain within an area bounded by the midpart of the clavicle and the deltoid insertion were eligible for inclusion in the study. Forty-two subjects agreed to participate, and four of them were lost to follow-up. Twenty clinical tests, radiography, bone-scanning, magnetic resonance imaging, and an acromioclavicular joint injection test were performed on all patients. The patients were divided into two groups according to whether they had a > or =50% decrease in pain following the acromioclavicular joint injection. Statistical analysis, including multivariate regression analysis, was performed in order to evaluate the diagnostic effectiveness of the various tests. RESULTS: Acromioclavicular joint pain was confirmed in twenty-eight of the thirty-eight patients. The most sensitive tests were examination for acromioclavicular tenderness (96% sensitivity), the Paxinos test (79%), magnetic resonance imaging (85%), and bone-scanning (82%), but these studies had low specificity. In the stepwise regression model, with the response to the injection used as the dependent variable, bone-scanning and the Paxinos test were the only independent variables retained. Patients with a positive Paxinos test as well as a positive bone scan had high post-test odds (55:1) and a 99% post-test probability of having pain due to pathological changes in the acromioclavicular joint. The likelihood ratio for patients with one negative test and one positive test was indeterminate (0.4:1). Patients with both a negative Paxinos test and a negative bone scan had a likelihood ratio of 0.03:1 for having acromioclavicular joint pain, which basically rules out the disorder. CONCLUSIONS: The highly sensitive tests had low specificity, and the highly specific tests had low sensitivity. However, the combination of a positive Paxinos test and a positive bone scan predicted damage to the acromioclavicular joint as the cause of shoulder pain with a high degree of confidence.

Acromioclavicular Joint↗

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.

Achilles Tendon↗

Treatment of shoulder dislocation: is a sling appropriate?

Acute anterior shoulder dislocations, when managed non-operatively, have traditionally been treated by placing the arm in a sling. There is no formal evidence that this treatment is of benefit. Three recently reported studies, one in cadavers and two in patients, suggest that the detachment of the structures in the front of the shoulder is made worse when the shoulder is placed in internal rotation, as when the arm is in a sling. By contrast, the structures are realigned when the arm is placed in external rotation. Shoulder dislocations, if managed non-operatively, should not be treated by placing arms in a sling. Rather, placing them in a splint or using a pillow so that the the arm is externally rotated should be considered.

Humans↗