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Nerve conduits are becoming increasingly popular for the repair of peripheral nerve injuries. Their ease of application and lack of donor site morbidity make them an attractive option for nerve repair in many situations. Today, there are many different conduits to choose in different sizes and materials, giving the reconstructive surgeon many options for any given clinical problem. However, to properly utilize these unique reconstructive tools, the peripheral nerve surgeon must be familiar not only with their standard indications but also with their functional limitations. In this review, the authors identify the common applications of nerve conduits, expected results, and shortcomings of current techniques. Furthermore, future directions for nerve conduit use are identified.

Purpose: Various animal models have been proposed to mimic the pathophysiologic process of intervertebral disc degeneration, a leading cause of back pain. The purpose of this study is to describe a minimally invasive technique via percutaneous needle puncture of the annulus fibrosus in New Zealand white rabbits. Methods: Under fluoroscopic guidance, an 18-gauge spinal needle was inserted 2 cm lateral to the midline spinous process. The needle was slowly advanced at approximately 45° angle until it was adjacent to the L5/L6 disc space. Lateral and anteroposterior views were used to verify correct needle position before advancing into the nucleus pulposus. The rabbits underwent weekly X-rays for 4 weeks to assess disc height index. MRI T2 relaxation was evaluated at week four to assess morphological changes. Discs were histologically graded on a 12-point scale to assess degeneration and compared to discs obtained from uninjured rabbits. Results: There were no complications associated with the percutaneous needle puncture procedure. All animals survived the duration of the experiment. Four weeks after injury, the disc height had progressively narrowed to approximately 50% of baseline. MRI assessment at the 4-week time point demonstrated a mean T2 relaxation time at the L5/L6 level that was 20.9% of the T2 relaxation time at the uninjured L4/L5 disc level ( p < 0.001). Histological analysis demonstrated lamellar disorganization of the annulus and decreased cellularity and proteoglycan content within the injured nucleus compared to uninjured control discs. Conclusion: The present study demonstrated a reliable technique of inducing an annular tear via a percutaneous needle puncture. Compared to open surgical approaches, the percutaneous model produces similar progressive disc degeneration while minimizing harm to the animal subjects. Clinical Relevance: The present study establishes a technique for the introduction of novel therapeutic agents to treat disc degeneration that may translate to future clinical trials.

The influence of age on rotator cuff function and muscle structure remains poorly understood. We hypothesize that normal aging influences rotator cuff function, muscle structure, and regulatory protein expression in an established rat model of aging.Seventeen rats were obtained from the National Institute on Aging. The supraspinatus muscles in 11 middle-aged (12 months old) and 6 old (28 months old) rats were studied for age-related changes in rotator cuff neuromuscular function by in vivo muscle force testing and electromyography (EMG). Changes in muscle structure and molecular changes were assessed with quantitative immunohistochemistry for myogenic determination factor 1 (MyoD) and myogenic factor 5 (Myf5) expression.Old animals revealed significantly decreased peak tetanic muscle force at 0.5 N and 0.7 N preload tension (P.05). The age of the animal accounted for 20.9% of variance and significantly influenced muscle force (P = .026). Preload tension significantly influenced muscle force production (P.001) and accounted for 12.7% of total variance. There was regional heterogeneity in maximal compound motor action potential (CMAP) amplitude in the supraspinatus muscle; the proximal portion had a significantly higher CMAP than the middle and distal portions (P.05). The expression of muscle regulatory factors MyoD and Myf5 was significantly decreased in old animals compared with middle-aged animals (P.05).The normal aging process in this rat model significantly influenced contractile strength of the supraspinatus muscle and led to decreased expression of muscle regulatory factors. High preload tensions led to a significant decrease in force production in both middle-aged and old animals.

Nonhuman primates have similar shoulder anatomy and physiology compared to humans, and may represent a previously underutilized model for shoulder research. This study sought to identify naturally occurring bony and muscular degeneration in the shoulder of nonhuman primates and to assess relationships between structural and functional aspects of the shoulder and measures of physical function of the animals. We hypothesized that age-related degenerative changes in the shoulders of nonhuman primates would resemble those observed in aging humans.Middle-aged (n = 5; ages 9.4-11.8 years) and elderly (n = 6; ages 19.8-26.4 years) female vervet monkeys were studied for changes in mobility and shoulder function, and radiographic and histologic signs of age-related degeneration.Four out of 6 (4/6) elderly animals had degenerative changes of the glenoid compared to 0/5 of the middle-aged animals (P = .005). Elderly animals had glenoid retroversion, decreased joint space, walked slower, and spent less time climbing and hanging than middle-aged vervets (P .05). Physical mobility and shoulder function correlated with glenoid version angle (P .05). Supraspinatus muscles of elderly animals were less dense (P = .001), had decreased fiber cross-sectional area (P .001), but similar amounts of nuclear material (P = .085). Degenerative rotator cuff tears were not observed in any of the eleven animals.The vervet monkey naturally undergoes age-related functional, radiographic and histological changes of the shoulder, and may qualify as an animal model for selected translational research of shoulder osteoarthritis.

Predisposition to Achilles tendon (AT) ruptures in middle-aged individuals may be associated with age-related changes to inherent passive biomechanical properties of the gastrocnemius-Achilles (GC-AT) muscle-tendon unit, due to known muscle-tendon structural changes in normal aging. The goal of this study was to determine whether the passive biomechanical response of the GC-AT muscle-tendon unit was altered with age in 6 young (8 months) and 6 middle-aged (24 months) F344xBN hybrid rats from the National Institute on Aging colony. Fung's quasilinear viscoelastic (QLV) model was used to determine in vivo history and time-dependent load-relaxation response of the GC-AT. Effective stiffness and modulus were also estimated using linear regression analysis. Fung's QLV revealed a significantly decreased magnitude of the relaxation response (parameter C, p=0.026) in middle-aged animals compared to young animals (0.108±0.007 vs. 0.144±0.015), with similar time-dependent viscous GC-AT properties (τ(1), τ(2)). The product of elastic parameters (A*B), which represents the initial slope of the elastic response, was significantly increased by 50% in middle-aged rats (p=0.014). Estimated GC-AT stiffness increased 28% at peak tensions in middle-aged rats (2.7±0.2 N/mm) compared to young rats (1.9±0.2 N/mm; p=0.036). While the limitations of this animal model must be considered, the changes we describe could be associated with the observation that GC-AT pathology and injury is more common in middle-aged individuals. Further studies are necessary to characterize the load-to-failure behavior of AT in middle-aged compared to young animals.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are often avoided by orthopaedic surgeons because of their possible influence on bone-healing. This belief stems from multiple studies, in particular animal studies, that show delayed bone-healing or nonunions associated with NSAID exposure. The purpose of this review was to critically analyze the quality of published literature that evaluates the impact of NSAIDs on clinical bone-healing. Methods: A MEDLINE and Embase search was conducted to identify all articles relating to bone and fracture-healing and the utilization of NSAIDs. All human studies, including review articles, were identified for further analysis. Non-English-language manuscripts and in vitro and animal studies were excluded. A total of twelve clinical articles and twenty-four literature reviews were selected for analysis. The quality of the clinical studies was assessed with a modified Coleman Methodology Score with emphasis on the NSAID utilization. Review articles were analyzed with regard to variability in the cited literature and final conclusions. Results: The mean modified Coleman Methodology Score (and standard deviation) was significantly lower (p = 0.032) in clinical studies that demonstrated a negative effect of NSAIDs on bone-healing (40.0 ± 14.3 points) compared with those that concluded that NSAIDs were safe (58.8 ± 10.3 points). Review articles also demonstrated substantial variability in the number of cited clinical studies and overall conclusions. There were only two meta-analyses and twenty-two narrative reviews. The mean number (and standard deviation) of clinical studies cited was significantly greater (p = 0.008) for reviews that concluded that NSAIDs were safe (8.0 ± 4.8) compared with those that recommended avoiding them (2.1 ± 2.1). Unanimously, all reviews admitted to the need for prospective randomized controlled trials to help clarify the effects of NSAIDs on bone-healing. Conclusions: This systematic literature review highlights the great variability in the interpretation of the literature addressing the impact of NSAIDs on bone-healing. Unfortunately, there is no consensus regarding the safety of NSAIDs following orthopaedic procedures, and future studies should aim for appropriate methodological designs to help to clarify existing discrepancies to improve the quality of care for orthopaedic patients. Clinical Relevance: This systematic review highlights the limitations in the current understanding of the effects of NSAIDs on bone healing. Thus, withholding these medications does not have any proven scientific benefit to patients and may even cause harm by increasing narcotic requirements in cases in which they could be beneficial for pain management. This review should encourage further basic-science and clinical studies to clarify the risks and benefits of anti-inflammatory medications in the postoperative period, with the aim of improving patient outcomes.

Background: Radiation-induced fibrosis (RIF) of musculoskeletal tissue is a common complication of radiation therapy for extremity soft-tissue sarcoma, with no standardized strategy for prevention and treatment. Angiotensin-(1-7) (Ang-[1-7]), a well-tolerated endogenous heptapeptide hormone with antitumor and antifibrotic properties, was tested as a radioprotectant for RIF and stiffening of irradiated muscles. Methods: Male CD-1 mice were randomized to one of three treatment groups: control, simulated sarcoma radiation therapy to the gastrocnemius and soleus muscles, or radiation therapy along with continuous Ang-(1-7) delivery initiated three days before radiation therapy. The biologically equivalent dose of radiation (∼100.3 Gy) absorbed by normal musculature during the course of radiation therapy for extremity sarcoma was delivered by means of four dose fractions of 7.3 Gy over two weeks. Fibrosis (n = 5 per group) and mechanical properties (n = 4 to 6 per group) of the muscles were measured at six weeks and four months after radiation therapy, and the intramuscular concentration of the profibrotic cytokines transforming growth factor-beta (TGF-β) and connective tissue growth factor (CTGF) (n = 8 to 10 per group) were measured at six weeks. Results: Interstitial (p < 0.01) and perivascular (p < 0.05) fibrosis increased significantly in the muscles treated with radiation therapy alone versus the nonirradiated controls at both six weeks (interstitial, +89%; perivascular, +112%) and four months (interstitial, +154%; perivascular, +88%). The muscles treated with radiation alone also exhibited increased tension (p < 0.01) versus nonirradiated controls at both six weeks (+779%) and four months (+1761%) when placed under 5% strain, and at four months (+1390%; p < 0.001) under 10% strain. At four months, muscle stiffness had increased in the mice treated with radiation therapy alone (+90%; p = 0.002) compared with nonirradiated controls. TGF-β production was also greater in this group at six weeks (+37%; p = 0.06) versus control. Ang-(1-7) administration prevented RIF and stiffening, with no differences observed for any other outcome between those receiving radiation therapy with Ang-(1-7) and the nonirradiated controls. Likewise, Ang-(1-7) mitigated the increase in TGF-β and CTGF concentration from radiation therapy. Conclusions: Ang-(1-7) attenuated RIF, stiffening, and production of profibrotic cytokines that were elevated in mouse skeletal muscles after simulated radiation therapy for extremity sarcoma. Clinical Relevance: Ang-(1-7) may serve as a potential therapy for the prevention of RIF in patients who require radiation therapy as adjuvant treatment for soft-tissue sarcoma.

The purpose of this article is to review basic science studies using various animal models for rotator cuff research and to describe structural, biomechanical, and functional changes to muscle following rotator cuff tears. The use of computational simulations to translate the findings from animal models to human scale is further detailed. A comprehensive review was performed of the basic science literature describing the use of animal models and simulation analysis to examine muscle function following rotator cuff injury and repair in the ageing population. The findings from various studies of rotator cuff pathology emphasize the importance of preventing permanent muscular changes with detrimental results. In vivo muscle function, electromyography, and passive muscle–tendon unit properties were studied before and after supraspinatus tenotomy in a rodent rotator cuff injury model (acute vs chronic). Then, a series of simulation experiments were conducted using a validated computational human musculoskeletal shoulder model to assess both passive and active tension of rotator cuff repairs based on surgical positioning. Outcomes of rotator cuff repair may be improved by earlier surgical intervention, with lower surgical repair tensions and fewer electromyographic neuromuscular changes. An integrated approach of animal experiments, computer simulation analyses, and clinical studies may allow us to gain a fundamental understanding of the underlying pathology and interpret the results for clinical translation.

BACKGROUND Surgical repair of large chronic rotator cuff tears can be technically demanding because it requires manipulation of a muscle-tendon unit that is scarred, retracted, and stiffer than normal, all of which contribute to increased tension at the repair site. The purpose of the present study was to characterize the in vivo rotator cuff muscle-tendon unit function after acute and chronic injury at surgically relevant preload tensions. METHODS Sixty-two Sprague-Dawley rats were divided into a healthy, uninjured (control) group (n = 22), an acute injury group (n = 20), and a chronic injury group (n = 20) and underwent in vivo muscle force testing and electromyographic testing of the supraspinatus muscle-tendon unit at various preload tensions. RESULTS Preload tension affected the maximum supraspinatus muscle contractile force in all groups (p < 0.05). At the peak tension required to repair an acute tear, there was a 28% to 30% reduction in maximum tetanic contraction amplitude in all groups (p < 0.05). At the peak tension required to repair a chronic tear, there was a 40% to 53% reduction in maximal tetanic contraction amplitude in all groups (p < 0.05). The uninjured (control) group showed increased muscle endurance (p < 0.05) in comparison with the acute injury and chronic injury groups at all preload tensions. The chronic injury group showed reduced compound motor action potential amplitude (p < 0.05). CONCLUSIONS Both the acute and chronic injury groups demonstrated functional impairment related to increasing preload tensions. Higher repair tensions, associated with the chronic injury setting, resulted in greater functional impairment. The present study also demonstrates an association between increased time from rotator cuff tendon injury and impaired in vivo rotator cuff muscle electromyographic findings.

The diagnosis and management of complex regional pain syndrome is often challenging. Early diagnosis and intervention improve outcomes in most patients; however, some patients will progress regardless of intervention. Multidisciplinary management facilitates care in complex cases. The onset of signs and symptoms may be obvious or insidious; temporal delay is a frequent occurrence. Difficulty sleeping, pain unresponsive to narcotics, swelling, stiffness, and hypersensitivity are harbingers of onset. Multimodal treatment with hand therapy, sympatholytic drugs, and stress loading may be augmented with anesthesia blocks. If the dystrophic symptoms are controllable by medications and a nociceptive focus or nerve derangement is correctable, surgery is an appropriate alternative. Chronic sequelae of contracture may also be addressed surgically in patients with controllable sympathetically maintained pain.

Ischemic heart disease remains one of the most common causes of mortality in developed countries. Recently, stem cell therapy is being considered for treating ischemic heart diseases. On the other hand, there has been evidence of chondro-osteogenic mass formation after stem cell injection in the heart. In a recent publication, Chiavegato et al. ( J Mol Cell Cardiol. 42 (2007) 746–759) has suggested that amniotic fluid-derived stem (AFS) cells cause chondro-osteogenic masses in the infarcted heart. The goal of the current study was to further examine the formation of such masses, specifically, the role of AFS cells in this process. Our results confirm the presence of similar bone-like masses in the left ventricular wall of infarcted rats; however, this phenomenon occurred independent of AFS cell injection into the myocardium. Moreover, AFS cell injection did not increase the presence of chondro-osteogenic masses. Echocardiographic analysis of large infarctions in rats frequently revealed the presence of echogenic structures in the left ventricular wall. We further demonstrated a significant relationship between the infarction size and chondro-osteogenic formation and subsequent decrease in cardiac function. Collectively, our study indicates that chondro-osteogenic differentiation can take place in infarcted rat heart independent of cell injection. These results have significant implications for future design and testing of stem cell therapy for treatment of cardiac muscle diseases.

The chemical denervation that results from botulinum neurotoxin A (BoNT-A) causes a temporary, reversible paresis that can result in easier surgical manipulation of the muscle-tendon unit in the context of tendon rupture and repair. The purpose of the study was to determine whether BoNT-A injections can be used to temporarily and reversibly modulate active and passive skeletal muscle properties.Male CD1 mice weighing 40-50 g were divided into a 1-week postinjection group (n = 13: n = 5 saline and n = 8 BoNT-A) and a 2-week postinjection group (n = 17: n = 7 saline and n = 10 BoNT-A). The animals had in vivo muscle force testing and in vivo biomechanical evaluation.There was a substantial decline in the maximal single twitch amplitude (p.05) and tetanic amplitude (p.05) at one week and at 2 weeks after BoNT-A injection, when compared to saline-injected controls. BoNT-A injection significantly reduced the peak passive properties of the muscle-tendon unit as a function of displacement at one week (p.05). Specifically, the stiffness of the BoNT-A injected muscle-tendon unit was 0.417 N/mm compared to the control saline injected group, which was 0.634 N/mm, a 35% reduction in stiffness (p.05).Presurgical treatment with BoNT-A might improve the surgical manipulation of the muscle-tendon unit, thus improving surgical outcomes. The results implicate neural tone as a substantial contributor to the passive repair tension of the muscle-tendon unit. The modulation of neural tone through temporary, reversible paresis is a novel approach that might improve intraoperative and postoperative passive muscle properties, allowing for progressive rehabilitation while protecting the surgical repair site.

Complex regional pain syndrome (CRPS) after an emergent or elective upper extremity surgery may complicate recovery, delay return to work, diminish health-related quality of life, and increase the likelihood of poor outcomes and/or litigation. CRPS after hand surgery is not uncommon and may complicate postoperative care. Early diagnosis and treatment of CRPS is critical for optimal patient outcomes. This article discusses the diagnosis, physiology, and management of postsurgical CRPS that occurs after hand surgery.

Background: Despite the increased use of arthroscopy in pediatric orthopaedics, there is a paucity of data regarding the potential long-term effects of this procedure on the immature physis. The purpose of this study was to test the hypothesis that elevated intra-articular pressures used during arthroscopic surgery do not result in growth disturbances or morphologic alterations in the epiphyseal plate. Methods: Twenty-seven 6-week-old skeletally immature New Zealand white rabbits were divided into experimental (n = 21) and control groups (n = 6). In the experimental group, a hydraulic pump was used to pressurize 1 randomly assigned knee joint per rabbit to intra-articular pressures of 120mm Hg for 2 hours. In the control group, rabbits received a sham intervention. All rabbits were killed at 6 months of age (skeletal maturity), and their tissues were evaluated grossly, radiographically, and histologically. Data collection included gross measurements (femur and tibia lengths, evaluation of varus/valgus angulation, and knee joint range of motion) and histologic analyses to determine whether morphologic changes were present in the articular cartilage or physis. Confidence intervals were used to test for statistical equivalence. Results: The pressurized and control groups had statistically equivalent gross measurements. No significant articular cartilage or physeal lesions were identified in histologic sections or radiographic studies. Conclusion: This study provided no evidence that arthroscopic pressurization of the knee joint to 120 mm Hg for 2 hours significantly affected physeal growth in a skeletally immature rabbit model. Clinical Relevance: This study provides the first direct evidence that arthroscopic pressurization of immature joints has no clinically significant adverse long-term effects. Therefore, novel uses of arthroscopy in pediatric patients should be explored without undue concern with regard to premature physeal closure.

Botulinum neurotoxins are among the most potent toxins found in nature, and are produced by Clostridium botulinum , an anaerobic, gram-positive, spore-forming rod-shaped bacterium1. There are seven known serotypes of botulinum neurotoxins (termed A, B, C1, D, E, F, G) that cleave soluble N-ethyl-maleimide-sensitive factor attachment receptor (SNARE) proteins, preventing effective release of neurotransmitters across specialized synaptic junctions. Blocking SNARE protein function within neuromuscular junctions produces flaccid paralysis, results in anhidrosis within sweat glands, and increases nutritional blood flow in vascular beds. On the basis of these findings, it was hypothesized that controlled injections of botulinum neurotoxins could be used to treat neuromuscular disorders. The benefits of botulinum neurotoxin injections in the treatment of various neurological disorders have captured the attention of physicians from multiple specialties and have contributed to the widespread use of botulinum neurotoxins in modern medicine2. Currently, only botulinum neurotoxin type-A (BoNT-A) and B (BoNT-B) serotypes are approved by the U.S. Food and Drug Administration. The mandated labeling includes the following therapeutic and anesthetic indications: (1) treatment of cervical dystonia in adults; (2) treatment of strabismus and blepharospasm associated with dystonia, including benign essential blepharospasm or seventh cranial nerve disorders in patients who are twelve years of age or older; (3) treatment of severe primary axillary hyperhidrosis; and (4) treatment of severe glabellar lines associated with corrugator and/or procerus muscle activity in patients who are sixty-five years of age or younger. This article outlines the role of botulinum toxins, particularly type A, as a therapeutic modality in musculoskeletal conditions on the basis of the peer-reviewed literature and the personal experience of the authors. Some of the information presented in this article describes off-label indications for drugs as defined by the Food and Drug Administration. The doses, side effects, techniques, and information reflect the …

Purpose The management of peripheral nerve injuries with segmental defects is a challenge to both patient and surgeon. Repairs under tension have a poor prognosis; sensory nerve allografts have donor site morbidity and suboptimal motor recovery, but remain the gold standard. The development of conduit-based repair strategies has evolved and these are promising for sensory nerves and short defects; however, no conduit filler is clinically available that improves motor recovery equivalent to sensory autografts. In this study, motor recovery using keratin-based hydrogel filler was compared with that for sensory nerve autografts and empty conduits. Methods Fifty-four mice were randomized into 3 treatment groups: empty conduit, sural nerve autograft, and keratin hydrogel-filled conduit. Animals were followed for 6 weeks, 3 months, and 6 months. Outcomes included compound motor action potential (CMAP), nerve area, myelinated axon number and density, and myelinated axon diameter. Results Neuromuscular recovery with keratin was greater than with empty conduits in most outcome measures. Nerves that regenerated through the keratin hydrogel had lower conduction delays, greater amplitudes, more myelinated axons, and larger axons than nerves that regenerated through empty conduits. Sensory nerve autografts and keratin hydrogel were statistically equivalent in CMAP measurements at 6 months. Moreover, keratin-filled conduits demonstrated greater axon density and larger average axon diameter than both empty conduits and autograft at 6 months. Conclusions In a mouse tibial nerve model, keratin hydrogels significantly improved electrophysiological recovery, compared with empty conduits and sensory nerve autografts, at an early time point of regeneration. Keratin hydrogels also produce long-term electrical and histological results superior to empty conduits and equivalent to sensory nerve autografts.

Evaluation of vascular disorders of the upper extremity requires an anatomic and functional approach. The combination of a good history and physical examination, laboratory testing, and specialized vascular laboratory studies will help detect any underlying collagen vascular disease or coagulopathy and provide physiologic-specific and patient-oriented management. This paper reviews the currently available noninvasive modalities for the evaluation of upper-extremity perfusion.

Background: Tendon-repair techniques have evolved to increase the construct strength of the repair site in order to permit early active range of motion without tendon gap or rupture. The present study evaluated the hypothesis that the injection of botulinum neurotoxin type-A (BoNT-A) into the gastrocnemius muscle will reduce the active force production of that muscle below the force required to rupture the associated, repaired Achilles tendon. Methods: Seventy-nine rat Achilles tendons were surgically bisected and were repaired with use of a two-strand core suture with a running epitenon repair. After the repair, the animals were treated with unilateral intramuscular (gastrocnemius) injections of either BoNT-A (6 U/kg body weight) (thirty-seven rats) or saline solution (forty-two rats). Operatively treated ankles were fixed in the neutral position with a percutaneous pin for the first two days after surgery. Unrestricted ankle motion and weight-bearing were allowed after the second postoperative day. An assessment of gap formation or rupture at the repair site, electrophysiologic measurements of force applied to the tendon, and an assessment of the strength of the repaired tendon were performed. Results: Intramuscular BoNT-A injections produced a significant, reversible reduction in active muscle force (p < 0.007). Twitch and tetanus contractions decreased to approximately 25% of the values for the control side within one week, remained at

The burden of chronic soft tissue inflammation and neuropathic pain on individuals and society is substantial. This study was conducted to evaluate the H-wave device--an innovative form of treatment for chronic pain and inflammation--in patients with persistent pain associated with injuries or conditions affecting the upper or lower extremities or the back. Patients with at least moderate pain despite conventional therapy were included in a systematic survey after they had been given 2 to 6 wk of treatment with the H-wave device. Measures of improvement involved the proportion of patients with diminished medication requirements, improved function, or pain relief greater than 25%. More than 60% of patients with pain in the lower extremities, upper extremities, or back experienced pain relief exceeding 25%. The proportion of patients whose function improved and who were able to perform a new activity was consistently greater than 50% across the 3 anatomic subgroups. More than 40% of patients in each group were able to reduce or completely eliminate the use of pain medications. These benefits of treatment were independent of the type of pain therapy administered previously. In each anatomic subgroup, the proportion of patients who reported improvement on more than 1 of the 3 endpoints was significantly higher than the expected response to placebo therapy (P

BACKGROUND Controlled joint extension followed by gradual distraction with use of an external fixator may facilitate primary repair of peripheral nerve defects by permitting end-to-end repair without tension. The hypothesis of the present study was that gradual lengthening of nerve repairs with use of incremental distraction would provide superior results compared with grafting or repair under tension. METHODS A median nerve segment measuring four times the diameter of the nerve was resected in thirty-six rabbits to create a 7-mm gap in the nerve. Neurorrhaphy was performed with use of one of three techniques. In Group 1 (cable graft), a tension-free medial antebrachial cutaneous graft was placed to allow full range of motion of the elbow postoperatively. In Group 2 (end-to-end repair without distraction), the elbow was externally fixed in hyperflexion and the nerve was repaired end-to-end. At fourteen days, the fixator was removed and unprotected elbow motion was permitted. In Group 3 (end-to-end repair with gradual distraction), the elbow was externally fixed in hyperflexion and primary neurorrhaphy was performed. At fourteen days, the elbow was extended 10 degrees every other day with use of the articulated external fixator until full extension was achieved. Median nerve amplitude, latency, and nerve-conduction velocity; flexor digitorum superficialis single-twitch force generation and maximum tetanic force generation; muscle mass; and elbow range of motion were measured at three or six months. In addition, histologic analysis of the median nerve distal to the repair site and the morphometry of the neuromuscular junction in the flexor digitorum superficialis were performed at six months. RESULTS All rabbits regained full active and passive range of motion. At three months, the nerve-conduction velocities in Groups 2 and 3 were significantly greater than that in Group 1. At six months, the nerve-conduction velocities and amplitudes in Group 3 were significantly greater than those in Groups 1 and 2. At six months, the tetanic force in Group 3 was significantly greater than those in Groups 1 and 2. There were no significant differences in muscle mass among the groups. There were no significant differences in histological findings among the three groups, although there was a trend toward larger fiber size in Group 3 as compared with the other two groups. The neuromuscular junctions in Group 3 had a significantly larger surface area than did those in Group 1 (p = 0.002) and Group 2 (p = 0.034). CONCLUSION The use of an articulated external fixator and controlled gradual distraction appears to facilitate the treatment of peripheral nerve defects.

Staphylococcus aureus is the bacterial pathogen which is responsible for approximately 80% of all cases of human osteomyelitis. It can invade and remain within osteoblasts. The fate of intracellular Staph. aureus after the death of the osteoblast has not been documented. We exposed human osteoblasts to Staph. aureus. After infection, the osteoblasts were either lysed with Triton X-100 or trypsinised. The bacteria released from both the trypsinised and lysed osteoblasts were cultured and counted. Colonies of the recovered bacteria were then introduced to additional cultures of human osteoblasts. The number of intracellular Staph. aureus recovered from the two techniques was equivalent. Staph. aureus recovered from time zero and 24 hours after infection, followed by lysis/trypsinisation, were capable of invading a second culture of human osteoblasts. Our findings indicate that dead or dying osteoblasts are capable of releasing viable Staph. aureus and that Staph. aureus released from dying or dead osteoblasts is capable of reinfecting human osteoblasts in culture.

Background:Ice is applied following a soft-tissue injury on the basis of clinical information. This study investigates the relationship between ice therapy (cryotherapy) and edema by determining microvascular permeability before and after contusion with and without ice therapy and provides data supp

Background Longitudinal studies of upper extremity aging in humans include logistical concerns that animal models can overcome. The vervet is a promising species with which to study aging-related processes. However, age-related changes in upper extremity muscle structure have not been quantified in this species. This study measured age-related changes to muscle structure, examined relationships between muscle structure and measures of physical performance, and evaluated the presence of rotator cuff tears. Methods Muscle structure (volume, optimal fiber length, and physiologic cross-sectional area (PCSA)) of 10 upper extremity muscles was quantified from the right upper limb of 5 middle-aged and 6 older adult female vervets. Results Total measured PCSA was smaller ( P = .001) in the older adult vervets than in the middle-aged vervets. Muscle volume reduction predominate the age-related reductions in PCSA. Total measured PCSA was not correlated to any measures of physical performance. No rotator cuff tears were observed. Supraspinatus volume was relatively larger and deltoid volume relatively smaller in the vervet compared with a human. Conclusions The vervet is an appropriate translational model for age-related upper extremity muscle volume loss. Functional measures were not correlated to PCSA, suggesting the vervets may have enough strength for normal function despite loss of muscle tissue. Reduced relative demand on the supraspinatus may be responsible for the lack of naturally occurring rotator cuff tears.

Major accomplishments this year include successful seeding of AFS into ANA. This accomplishment also documented that these cells remained viable up to 72 hours after seeding. The seeded constructs were used to repair critical-sized, large gap nerve injury in rats and their functional recovery was monitored longitudinally using digital video gait analysis as well as electrophysiologic and histologic outcomes. The data analysis is not complete, but preliminary data indicate that this AFS seeded ANA used for nerve repair results in an improved functional outcome for the rats compared to a nerve autograft, the current gold standard for tension-free repair of transected peripheral nerves. The coming year will utilize these techniques for repairing large-gap (6 cm) nerve injuries in non-human primates. These represent a more translational model of peripheral nerve injury and repair.

Background: Advanced patient age is associated with recurrent tearing and failure of rotator cuff repairs clinically; however, basic science studies have not evaluated the influence of aging on tendon-to-bone healing after rotator cuff repair in an animal model. Hypothesis/Purpose: This study examined the effect of aging on tendon-to-bone healing in an established rat model of rotator cuff repair using the aged animal colony from the National Institute on Aging of the National Institutes of Health. The authors hypothesized that normal aging decreases biomechanical strength and histologic organization at the tendon-to-bone junction after acute repair. Study Design: Controlled laboratory study. Methods: In 56 F344xBN rats, 28 old and 28 young (24 and 8 months of age, respectively), the supraspinatus tendon was transected and repaired. At 2 or 8 weeks after surgery, shoulder specimens underwent biomechanical testing to compare load-to-failure and load-relaxation response between age groups. Histologic sections of the tendon-to-bone interface were assessed with hematoxylin and eosin staining, and collagen fiber organization was assessed by semiquantitative analysis of picrosirius red birefringence under polarized light. Results: Peak failure load was similar between young and old animals at 2 weeks after repair (31% vs 26% of age-matched uninjured controls, respectively; P > .05) but significantly higher in young animals compared with old animals 8 weeks after repair (86% vs 65% of age-matched uninjured controls, respectively; P < .01). Eight weeks after repair, fibroblasts appeared more organized and uniformly aligned in young animals on hematoxylin and eosin slides compared with old animals. Collagen birefringence analysis of the tendon-to-bone junction demonstrated that young animals had increased collagen fiber organization and similar histologic structure compared with age-matched controls (53.7 ± 2.4 gray scales; P > .05). In contrast, old animals had decreased collagen fiber organization and altered structure compared with age-matched controls (49.8 ± 3.1 gray scales; P < .01). Discussion: In a rat model of aging, old animals demonstrated diminished tendon-to-bone healing after rotator cuff injury and repair. Old animals had significantly decreased failure strength and collagen fiber organization at the tendon-to-bone junction compared with young animals. This study implies that animal age may need to be considered in future studies of rotator cuff repair in animal models. Clinical Relevance: With increasing age and activity level of the population, the incidence of rotator cuff tears is predicted to rise. Despite advances in rotator cuff repair technique, the retear rate remains specifically high in elderly patients. The findings of this research suggest that aging negatively influences tendon-to-bone healing after rotator cuff repair in a validated animal model.

This article details the presentation and evaluation of occlusive, vasospastic, and mixed vascular disorders. Indications and techniques of nonoperative management and surgical techniques of vascular reconstruction and periarterial sympathectomy are presented. Copyright © 2001 by the American Society for Surgery of the Hand

This study was designed to detail the history and symptoms of symptomatic radial artery vaso-occlusive disease and to evaluate the results of radial artery reconstruction. Thirteen patients with symptomatic vaso-occlusive disease of the radial artery unresponsive to management by nonoperative modalities were managed with arterial reconstruction. All cases were treated with reversed interpositional vein grafting from the radial artery in the forearm (end-to-side) to the deep arch distally (end-to-end). Patients completed preoperative and postoperative assessments of symptoms and function, cold sensitivity (cold intolerance), and digital microvascular perfusion (isolated cold stress test evaluation with laser Doppler fluxmetry). At the follow-up examination all vascular grafts were patent, as determined by Allen's testing and Doppler ultrasound. The patients reported symptoms and functional status that demonstrated significant improvement following reconstruction. Microvascular evaluations demonstrated a significant improvement in digital microvascular perfusion as assessed by laser Doppler fluxmetry and digital temperature recordings with a resultant resolution of ischemic pain, numbness, and ulceration.

This study assessed the accuracy of arteriography and laser Doppler perfusion imaging (LDPI) as predictors of digital ischemia and correlated upper extremity symptoms, function, and nutritional flow with arteriographic and laser Doppler assessments. Multiple-level occlusive disease was documented in 25 hands (23 patients) by arteriography. LDPI demonstrated one or more hypoperfused digits in 17 hands. Patient questionnaires were used to assess upper extremity symptoms, pain, cold sensitivity, and function. Spearman correlation coefficients indicated that arteriography is a poor indicator of nutritional perfusion as measured by LDPI. Neither arteriography or laser Doppler perfusion imaging served as an indicator of the severity of cold intolerance. However, upper extremity symptoms and functional status correlated with both laser Doppler measurements and the level of cold sensitivity. Laser Doppler perfusion imaging and arteriographic analysis provide complimentary data in the evaluation of upper extremity ischemia.

The effects of transdermal nicotine-assisted smoking cessation on digital perfusion and health-related quality of life were assessed in 10 chronic smokers. Components of digital blood flow were evaluated by digital temperature and laser Doppler fluxmetry before, during, and after a standardized cold challenge. Nutritional flow was measured by vital capillaroscopy; a quantitative perfusion profile was obtained by laser Doppler perfusion imaging. A battery of validated measures were used to evaluate health-related quality of life. The microvascular response of smokers was evaluated before smoking cessation and at 2 and 7 days after smoking cessation and was compared with the response of nonsmoking controls. Results demonstrated that a (1) cutaneous microvascular perfusion was lower in smokers than nonsmokers, (2) the acute administration of transdermal nicotine did not decrease cutaneous perfusion, (3) smoking cessation and transdermal nicotine normalized digital microvascular perfusion by 7 days, and (4) transdermal nicotine and smoking cessation did not negatively impact health-related quality of life.

A rabbit ear model of the human digit was utilized to determine the vascular response to peripheral sympathectomy. Vascular responses were evaluated by subjecting chronically instrumented rabbits to a cold stress before and after sympathectomy surgery. The typical response to cold stress is for ear temperatures and auricular cutaneous perfusion to decrease during the cooling phase of the test and to increase toward baseline levels during the rewarming phase after cold exposure. Following peripheral sympathectomy, ear temperatures were significantly increased during both the cooling and rewarming phase of the cold stress test although overall ear perfusion and skin perfusion were not different from sham-operated rabbits. The responses observed in the rabbit ear following peripheral sympathectomy appear to mimic those noted in patients receiving digital peripheral sympathectomies for the treatment of refractory pain and ulceration. Peripheral sympathectomy may result in clinical improvements in patients because it improves both total digital and nutritional cutaneous blood flow. Peripheral sympathectomy in normal rabbit ears does not result in altered perfusion patterns with cold exposure although ear temperature is significantly higher. This pattern of changes suggests that the distribution of extremity perfusion is altered even though overall extremity perfusion and cutaneous perfusion per se are not significantly different from sham-operated controls. Complete sympathectomy was accompanied by a persistent increase in ear temperature and a dissociation between conductance and microvascular perfusion. Auricular conductance was transiently increased and then decreased to levels below preoperative control values. Microvascular perfusion is decreased immediately following amputation/replantation and thereafter increases.

Vasospastic disorders of the upper extremity are common and often difficult to treat. Using the proposed classification system (Table 2) allows management based upon pathologic condition, physiologic staging, and response to treatment. Identifying patients in this way also helps in determining which treatments are most appropriate. The basic approach to management includes environmental and behavioral modifications including cessation of tobacco use, protection of hands, and avoidance of situations that trigger the vasospastic response. Pharmacologic therapy may provide good results in a majority of patients. Surgical intervention is reserved for patients with vaso-occlusion, ischemia, and refractory symptoms in spite of attempts at medical management. Surgical options include vascular reconstruction, peripheral sympathectomy, or a combination of techniques. The goal of medical and surgical management is to increase total or nutritional blood flow in the digits.

OBJECTIVE Topical application of subatmospheric pressure (TASAP) promotes faster wound healing, but tissue effects are not entirely understood. This study investigated microvascular effects of TASAP in striated muscle with the hypothesis being that TASAP elicits arteriolar vasodilation and decreases interstitial accumulation of protein. METHODS Rat cremasteric microcirculation was directly examined in two experiments utilizing a novel technique. First, TASAP was applied to the cremaster in three experimental groups and a non-TASAP control group. Arteriolar diameters were directly measured before and after TASAP. In experiment two, intravascular fluorescein isothiocyanate (FITC)-labeled albumin and topical leukotriene B4 (LTB4) were delivered to the cremaster. Microvascular permeability was assessed by measuring the accumulation/disappearance of FITC-albumin in the interstitial tissue. RESULTS TASAP produced significant arteriolar vasodilation compared with control values. The mean maximum percent increase in diameter with TASAP was 8.70% at -2 kPa (p < 0.05), 7.16% at -4 kPa (p < 0.05), and 10.43% at -6 kPa (p < 0.01). TASAP decreased interstitial FITC-albumin by 26.3% (p < 0.008) following LTB4; the control group showed a steady increase in interstitial FITC-albumin. CONCLUSIONS These results support the hypothesis that TASAP elicits significant arteriolar vasodilation with a subsequent increase in blood flow as well as a decrease in interstitial protein accumulation.

SUMMARY RSD can be approached using objective criteria in a logical and systematic fashion. Frustration during treatment is common because (1) the pathophysiology of RSD is incompletely understood, (2) there is significant variation in presentation because of disparate premorbid anatomy and physiology, and (3) the natural history may be affected by incomplete treatment. Therapeutic efforts that theoretically should be effective may fail, and a trial-and-error approach is often mandatory. In spite of vigorous intervention using all known strategies, patients may continue to have pain and disability that progresses to stiffness and arthrofibrosis. Early recognition and prompt intervention, however, provide the best opportunity for clinical improvement.

The management of reflex sympathetic dystrophy with oral, topical, and parenteral medications is complex. This article outlines the pharmacologic options available to treat dystrophic pain, provides an overview of mechanisms-of-action, and defines relative indications for administration.

Microvascular physiology following peripheral artery sympathectomy was evaluated in seven hands with refractory pain (n = 7) and ulceration (n = 7) by serial isolated cold stress testing, which measures digital temperature and cutaneous perfusion (laser Doppler fluxmetry). All patients (n = 6) had vasospasm (secondary Raynaud's phenomenon) and arteriographically proven digital and palmar occlusive disease. Microcirculatory flow responses were correlated with symptoms and signs (including ulcer healing) before and after (2-8 weeks, 12-15 weeks, and 24 weeks) peripheral sympathectomy. Baseline data were compared with those of controls (n = 7 extremities). Following surgery, all seven hands had diminished pain; six had ulcer healing and one had ulcer reduction. Isolated cold stress testing demonstrated abnormalities in temperature and laser Doppler fluxmetry response between patients and controls. Although total flow (reflected by temperature) was not significantly increased after surgery, peripheral sympathectomy increased nutritional flow in these patients with combined vasospastic vessels and occlusive injury. The clinical changes observed following peripheral sympathectomy appear to be related to postsurgical correction of abnormal arteriovenous shunting and to improved nutritional blood flow to ischemic areas. This accounts for the resultant diminution of pain and healing of ulcers observed in these patients after surgery.

Background: This study evaluated the properties of scaffold derived from freeze-dried human Achilles tendon allograft for use in anterior cruciate ligament (ACL) reconstruction. Our hypothesis was that such an allograft could be processed using a method to remove cellular and infectious material, producing a cytocompatible, architecturally modified scaffold possessing tensile properties suitable for ACL reconstruction. Methods: Fifty-two allografts were provided by a tissue bank. Twenty-one were used as controls to assess cellularity, DNA content, microarchitecture, porosity, cytocompatibility, and tensile properties in vitro (n = 13) and in vivo (n = 8). Thirty-one were processed to produce scaffolds that were similarly assessed for these properties in vitro (n = 23) and in vivo (n = 8). The elimination of added enveloped and nonenveloped viruses was also determined in vitro after each processing step. Results: A subjective decrease in cellularity and a significant decrease in DNA content were observed in the scaffolds compared with the allografts from which they had been derived. The porosity was increased significantly, and the scaffolds were cytocompatible in vitro. Processing resulted in significantly increased elongation of the scaffolds (138% of the elongation of the unprocessed allograft) during tensile testing. No other significant differences in tensile properties were observed in vitro or in vivo. The number of infiltrating host cells and the depth to which those cells infiltrated were significantly greater in the scaffolds. No enveloped viruses and only two of 108 nonenveloped viruses were detected in the scaffolds after processing, corresponding to a sterility assurance level of 0.2 × 10−7. Conclusions: Allografts were processed using a method that removed cellular and infectious material to produce a decellularized, cytocompatible, architecturally modified scaffold with tensile properties that differed minimally from those of human allograft tissue both in vitro and in vivo. The scaffold production process also resulted in an increase in porosity that led to increased cell infiltration in vivo. Clinical Relevance: Scaffolds derived from such tendon allografts have the potential to eliminate disease transmission and inflammation in recipients and to promote earlier and increased cell infiltration while retaining the initial tensile properties necessary to withstand rehabilitation after implantation.

The present review illustrates the state of the art of regenerative medicine (RM) as applied to surgical diseases and demonstrates that this field has the potential to address some of the unmet needs in surgery. RM is a multidisciplinary field whose purpose is to regenerate in vivo or ex vivo human cells, tissues, or organs to restore or establish normal function through exploitation of the potential to regenerate, which is intrinsic to human cells, tissues, and organs. RM uses cells and/or specially designed biomaterials to reach its goals and RM-based therapies are already in use in several clinical trials in most fields of surgery. The main challenges for investigators are threefold: Creation of an appropriate microenvironment ex vivo that is able to sustain cell physiology and function in order to generate the desired cells or body parts; identification and appropriate manipulation of cells that have the potential to generate parenchymal, stromal and vascular components on demand, both in vivo and ex vivo; and production of smart materials that are able to drive cell fate. © 2012 by Lippincott Williams and Wilkins.

Purpose Botulinum neurotoxin-A (BoNTA) is used to treat several disorders, including Raynaud phenomenon. Recent investigations cite toxin-induced increases in blood flow, but no mechanism for BoNTA's actions is proposed. This study hypothesized that local application of BoNTA causes arteriolar vasodilation through sympathetic blockade and results in increased blood flow. Methods Microvascular effects of BoNTA were assessed using a rat cremaster preparation. Cremaster microvascular diameters were measured in the muscle before and after treatment with the muscle paralytic agent gallamine triethiodide. Preparations were then treated with one of the following: BoNTA (4, 6, or 10 units), BoNTA dilution vehicle, or denatured BoNTA. Arteriolar diameters were measured repeatedly over the observation period. Additional preparations were treated with either tetrodotoxin or prazosin and rauwolscine before BoNTA to confirm that the observed vasodilatory responses were the result of sympathetic neural inhibition. Results The BoNTA application resulted in a significant dose-dependent vasodilation (13% to 15%) of observed cremaster arterioles. Control treatments did not cause vasodilation. Both tetrodotoxin and prazosin/rauwolscine treatments elicited similar vasodilatory effects, with no additional vasodilation elicited by BoNTA. Addition of sodium nitroprusside following BoNTA elicited further vasodilation. In addition, systemic arterial pressure was unaffected by the local administration of BoNTA. Conclusions Local application of BoNTA results in arteriolar dilation that yields an approximate 69% increase in blood flow, without changing systemic arterial pressure. A BoNTA-mediated vasodilation through sympathetic blockade is a likely mechanism to explain the increase in blood flow reported after treatment with the toxin. Clinical relevance The ability of BoNTA to inhibit sympathetic nervous input reduces vasoconstriction, which is the most likely mechanism for improvement seen in Raynaud phenomenon patients following BoNTA injection.

Background Despite surgical advances, repair of rotator cuff tears is associated with 20–70% incidence of recurrent tearing. The tension required to repair the torn tendon influences surgical outcomes and may be dependent on the gap length from torn tendon that must be spanned by the repair. Detailed understanding of forces throughout the range of motion (ROM) may allow surgeons to make evidence-based recommendations for post-operative care. Methods We used a computational shoulder model to assess passive tension and total moment-generating capacity in supraspinatus for repairs of gaps up to 3 cm throughout the shoulder (ROM). Findings In 60° abduction, increased gap length from 0.5 cm to 3 cm caused increases in passive force from 3 N to 58 N, consistent with those seen during clinical repair. For reduced abduction, passive forces increased substantially. For a 0.5 cm gap, tension throughout the ROM (elevation, plane of elevation, and rotation) is within reasonable limits, but larger gaps are associated with tensions that markedly exceed reported pull-out strength of sutures and anchors. Peak moment for a large 3 cm gap length was 5.09 Nm, a 53% reduction in moment-generating capacity compared to uninjured supraspinatus. Interpretation We conclude that shoulder posture is an important determinant of passive forces during rotator cuff repair surgery. Choosing postures that reduce forces intraoperatively to permit repair of larger gaps may lead to failure postoperatively when the shoulder is mobilized. For larger defects, loss of strength in supraspinatus may be substantial following repair even if retear is prevented.

SUMMARY Stress testing is an important element in the evaluation of upper extremity vascular perfusion. Advances in noninvasive testing provide mechanisms to evaluate the static structural characteristics of the arterial system, to define patent and nonpatent vessels to identify areas of thrombosis or occlusion, to evaluate arterial wall motility and elasticity, and to observe the nutritional capillary bed. To understand upper-extremity vascular function, however, some form of stress testing is crucial. The techniques discussed previously continue to evolve and serve only as examples of the potential of noninvasive tests evaluated before, during, and after stress. Stress testing provides techniques that allow us to understand the functional components of vascular perfusion and to monitor our attempts at interventions.

This preliminary report describes the use of a rat model developed to study in vivo the effect of anesthesia, contusion, and cryotherapy on skeletal muscle microcirculation by use of an implanted chamber. The diameters of arterioles and venules within the chamber were determined by photomicroscopy in the contusion study and by compound videomicroscopy in the anesthesia study; microvascular perfusion was determined by laser Doppler fluxmetry (LDF). Combined ketamine and xylazine anesthesia significantly reduced (P < 0.05) arteriolar and venular diameters by 32.4% and 37.8%, respectively, and average LDF measurements by 36.1%. Contusion significantly increased arteriolar diameters over baseline values (P < 0.05); cryotherapy did not alter arteriolar diameters but increased venular diameters (P < 0.05). It is hypothesized that this increase in venular diameter may, by increasing the surface area available for reabsorption, explain one mechanism by which cryotherapy decreases the edema of contusion. Use of this model should help to advance the understanding of microcirculatory dynamics following contusion and cryotherapy. © 1993 Wiley-Liss Inc.

A rabbit ear model has been developed in which arterial pressure, auricular blood flow conductance, and microvascular perfusion can be followed continuously in conscious animals. Conductance is measured with a transit-time flow probe placed around the auricular artery, arterial pressure is measured with an abdominal aortic catheter, and cutaneous microvascular perfusion is assessed using laser Doppler fluxmetry. Placement of a femoral vein catheter permits administration of vasoactive substances. To date, rabbits have been instrumented for 90 days or longer. Auricular and abdominal arterial pressures were equal, permitting the calculation of auricular artery conductance. Microvascular perfusion as measured by laser Doppler fluxmetry followed changes in overall blood flow. The presence of postsynaptic alpha 2-receptors was confirmed by determining auricular conductance before and after the administration of intravenous alpha-agonists. The development of this unique model will help to advance the understanding of the pathophysiology of human digital thermoregulatory vascular abnormalities.

Background: Interactions between the peripheral nervous system and the healing skeleton are poorly understood. Various clinical observations suggest that the nervous system interacts with and promotes fracture-healing. The purpose of this study was to examine the effect of selective sensory denervation on fracture-healing. Methods: Fifty-one Sprague-Dawley rats underwent unilateral placement of an intramedullary rod followed by creation of a standardized femoral fracture. One group of these rats underwent sensory denervation by means of a localized capsaicin injection, and the other did not. Subgroups were allocated for analysis of mRNA expression of collagen I and II and osteocalcin at three, seven, and fourteen days after the fracture. Additionally, histological examination was performed at four weeks; micro-computed tomography, at five weeks; and biomechanical testing, at six weeks. Results: The sensory-denervated group had significantly less collagen-I upregulation than the sensory-intact group at three days after the fracture (difference in means, forty-four-fold [95% confidence interval = 22.7 to 65.5-fold]; p < 0.001) and significantly less collagen-II upregulation at seven days after the fracture (difference in means, ninefold [95% confidence interval = 4.3 to 13.8-fold]; p < 0.001). In the sensory-denervated group, the fracture callus had a significantly larger cross-sectional area (difference in means, 15.6 mm2 [95% confidence interval = 0.78 to 30.5 mm2]; p = 0.043) and was less dense. Biomechanical testing revealed that sensory denervation significantly decreased the load to failure (difference in means, 28.7 N [95% confidence interval = 1.2 to 56.2 N]; p = 0.022). Conclusions: Sensory denervation negatively affects fracture-healing. These results offer insight into the nerve-bone interaction following injury. Clinical Relevance: These results are relevant to clinicians and researchers who are seeking to improve fracture-healing in patients with associated peripheral nerve injury or peripheral neuropathy.

Purpose Although recovery occurs in the majority of cases of brachial plexus birth palsy (BPBP), long-term shoulder disability is relatively common. The aim of this study was to establish an animal model to study BPBP-associated shoulder deformities. Methods A right-side C5, C6 root neurotomy was performed under the surgical microscope in 5-day-old Sprague-Dawley rats (N = 9). The contralateral side served as a control. The development of shoulder deformity and range of motion loss were followed longitudinally. Animals were killed 4 months after surgery. Both shoulders were harvested, decalcified, and transected in the axial plane for glenoid version measurement and shoulder histology. Results All animals developed shoulder internal rotation contracture within 4 weeks after the C5, C6 neurotomy. The average shoulder external rotation loss was 52° ± 7, 59° ± 10, and 82° ± 11 in comparison with the control side 1, 2, and 4 months after neurotomy, respectively. Glenoid version changed from 2° ± 2 of retroversion (left side) to 8° ± 3 of anteversion. Five shoulders were subluxated clinically with a pseudoglenoid formation observed radiographically. Histologic study demonstrated marked glenoid and humeral head deformities. Conclusions This neonatal rat model clearly demonstrated typical shoulder deformities similar to that resulting from Erb's palsy. This model can be useful in studying BPBP-associated shoulder deformities.

The use of periarterial sympathectomy (PAS) to manage chronic digital ischemia caused by scleroderma remains controversial. The duration of efficacy of PAS in managing scleroderma symptoms was evaluated by examining microvascular physiology, health-related quality of life, and patient satisfaction. Twenty-two patients (29 hands) with scleroderma, chronic vascular insufficiency, and a history of nonhealing digital ulcers unresponsive to nonsurgical treatment were evaluated. Isolated cold stress testing and laser Doppler fluxmetry measurements were used to evaluate microvascular perfusion before surgery and after a mean follow-up period of 31 months (range, 7-108 months). Digital temperatures did not change after surgery, but microvascular perfusion had increased significantly at a mean of 31 months in 22 hands. Health-related quality-of-life data were collected at a mean of 46 months (range, 11-108 months) after surgery. Subjective improvement (fewer ulcers, faster ulcer healing, and decreased pain) was reported for 18 of 22 patients (24 of 29 hands) at a mean follow-up period of 46 months; 6 patients remained ulcer free. Follow-up of scleroderma patients after PAS documented improved microvascular perfusion as evaluated by laser Doppler fluxmetry and by variable clinical results.