Search PubMed⌕ Search

Biomedical subjects

Susan E Mackinnon

Publications and source records attributed to Susan E Mackinnon.

At least 55 records · Page 3Linked to original sources
PubMed2004

Treatment of a proximal accessory nerve injury with nerve transfer.

OBJECTIVE AND HYPOTHESIS: This study presents a case report of a patient who sustained an iatrogenic proximal accessory nerve injury that was treated with a medial pectoral to accessory nerve transfer. STUDY DESIGN: Case study. MATERIALS AND METHODS: Chart of one patient who was treated with a medial pectoral to accessory nerve transfer was reviewed. RESULTS: Five months after excision of a branchial cyst that resulted in a very proximal injury to the accessory nerve, this patient underwent a medial pectoral to accessory nerve transfer. At final follow-up, 3 years after surgery, the patient had full abduction overhead with some residual shoulder/scapular discomfort and mild scapular winging. CONCLUSION: The medial pectoral to accessory nerve transfer provides a viable surgical option with good reinnervation of the trapezius muscle in patients with a proximal accessory nerve injury where standard nerve repair or graft techniques are not feasible.

Accessory Nerve↗
PubMed2004

Ulnar nerve injury associated with trampoline injuries.

OBJECTIVE: This study reports three cases of ulnar neuropathy after trampoline injuries in children. METHODS: A chart review was performed on children who sustained an ulnar nerve injury from a trampoline accident. In all cases, surgical intervention was required. RESULTS: Injuries included upper-extremity fractures in two cases and an upper-extremity laceration in one case. All cases required surgical exploration with internal neurolysis and ulnar nerve transposition. Nerve grafts were used in two cases and an additional nerve transfer was used in one case. All patients had return of intrinsic hand function and sensation after surgery. CONCLUSION: Children should be followed for evolution of ulnar nerve neuropathy after upper-extremity injury with consideration for electrical studies and surgical exploration if there is no improvement after 3 months.

Accidental Falls↗
PubMed2004

The surgical workforce crisis: rising to the challenge of caring for an aging America.

In the past century, both the field of surgery and the population it serves have markedly changed. The number of elderly individuals in the United States is rapidly increasing. However, this increase has not been accompanied by commensurate growth in the surgical workforce. As the demographic characteristics of medical students have become more diverse, medical student interest in surgical training has declined. These trends raise two fundamental questions. (1) Will there be enough surgeons to meet the needs of an aging United States population? (2) Who will these surgeons be?

Aged↗
PubMed2004

Force deficits in skeletal muscle after delayed reinnervation.

Using a rat hindlimb model, the authors tested the hypothesis that, in muscles reinnervated after long-term denervation, atrophy-dependent and atrophy-independent mechanisms operate independently to produce force deficits. In adult rats, gastrocnemius muscles were subjected to denervation via tibial nerve transection. Reconstruction of the nerve lesion was delayed for periods ranging from 2 weeks to 1 year. After a minimum recovery period of 6 months after nerve repair, muscle mass and maximum isometric tetanic force were measured and specific force was calculated for each muscle (n = 40 muscles from 23 animals). After recovery, observed deficits in muscle mass and maximum tetanic force were directly proportional to the denervation interval. On the other hand, the deficit in specific force was not proportional to the denervation interval; all groups in which the nerve reconstruction was delayed for a month or longer demonstrated a deficit of 30 percent to 50 percent. These data support our hypothesis that, after prolonged denervation followed by reinnervation, the magnitude of the deficit in whole muscle force does not parallel the deficit in specific force. These data support the idea that mechanisms governing muscle atrophy are independent of those resulting in specific force deficits.

Animals↗
PubMed2004

Anti-CD40 ligand antibody permits regeneration through peripheral nerve allografts in a nonhuman primate model.

Systemic immunosuppression is typically required to prevent allograft rejection. Antibody-based therapies that induce immune unresponsiveness represent an appealing alternative to nonspecific immunosuppression, which is often associated with significant morbidity. In mice, successful prevention of nerve allograft rejection has been demonstrated through interference with the CD40/CD40 ligand interaction. This study investigated the effectiveness of anti-CD40 ligand monoclonal antibody as single-agent therapy in preventing rejection and supporting nerve regeneration across long nerve allografts in nonhuman primates. Twelve outbred cynomolgus macaques were arranged into six genetically mismatched pairs, with each animal receiving a 5-cm ulnar nerve allograft in the right arm and a 5-cm autograft in the left arm. Mixed lymphocyte reaction assays were used to assess resulting immune unresponsiveness. Treated animals (n = 10) received anti-CD40 ligand monoclonal antibody 10 mg/kg one time, locally applied, and 20 mg/kg systemically on postoperative days 0, 1, 3, 10, 18, and 28, and then monthly. Untreated animals (n = 2) served as the untreated controls. At 4 or 6 months after transplantation, nerves were harvested for histological analysis. Four treated animals underwent an additional challenge after cessation of anti-CD40 ligand monoclonal antibody therapy and nerve graft harvests. Autogenous and allogeneic skin and nerve inlay grafting was performed to assess the permanence of immune unresponsiveness induced by anti-CD40 ligand monoclonal antibody. Animals that received anti-CD40 ligand monoclonal antibody demonstrated robust regeneration across nerve allografts, similar to that seen in the autograft control in the contralateral arm. The histomorphometric analysis of allografts in the untreated animals demonstrated significantly worse measurements compared with their matched autograft controls. Animals that received anti-CD40 ligand monoclonal antibody with concomitant skin allografts had virtually no evidence of nerve regeneration through allografts. Allogeneic skin and nerve allografts applied 2 to 12 months after withdrawal of anti-CD40 ligand monoclonal antibody therapy were consistently rejected. This study demonstrates that anti-CD40 ligand monoclonal antibody prevents rejection and allows regeneration of peripheral nerve allografts in nonhuman primates. The effect of anti-CD40 ligand monoclonal antibody appears to be transient, however, with restoration of immunocompetence shortly after withdrawal of therapy.

Animals↗
PubMed2004

Effect of tension on nerve regeneration in rat sciatic nerve transection model.

Excessive tension across a nerve repair is known to impair nerve regeneration. However, it is uncertain whether nerve grafting is necessary when end-to-end repair would result in only mild to moderate tension. This study investigated the effect of tension on nerve regeneration. Sciatic nerves of 48 Lewis rats were transected and then repaired primarily after resection of 0-, 3-, 6-, or 9-mm lengths of nerve. Postoperative tension levels were quantified using a tensometer. Robust nerve regeneration was observed at 4 weeks in all except the 9-mm repair group, which showed lower nerve fiber counts, percent neural tissue, and nerve density (P < 0.05) and decreased functional recovery. These data indicate that modest levels of tension are well tolerated, but nerve regeneration drops precipitously once a critical tension threshold is exceeded. This threshold was between 0.39 and 0.56 N in the model studied, corresponding to a nerve defect between 6 mm and 9 mm.

Animals↗
PubMed2004

A review of research endeavors to optimize peripheral nerve reconstruction.

This manuscript reviews studies relating to peripheral nerve allografts, neuroregenerative agents and end-to-side neurorrhaphy. With respect to peripheral nerve allografts, animal studies with the agents cyclosporin A, FK506 and rapamycin are reviewed and related to recent clinical experience. FK506 distinguishes itself as an agent capable of reversing acute rejection of a peripheral nerve allograft and an agent with some neuroregenerative properties. In addition to systemic immunosuppression, experience with agents purported to initiate a state of donor specific tolerance are discussed. Specifically, experimental studies with administration of ultraviolet B treated donor splenocytes, antibodies to cellular adhesion molecules and antibodies to components of the costimulatory pathway of immunosuppression are reviewed. The neuroregenerative properties of FK506 and related compounds are examined in animal models. Finally, the experimental finding that reinnervation following end-to-side neurorrhaphy is mostly sensory and related to the degree of axonal damage at the level of an epineurotomy or perineurotomy is discussed.

Animals↗
PubMed2003

Long-term limb allograft survival using anti-CD40L antibody in a murine model.

BACKGROUND: Costimulation blockade has been shown to be effective in achieving donor-specific immune unresponsiveness in models of organ transplantation. This study represents the first application of blockade of the CD40 costimulatory pathway to a murine model of limb allotransplantation. METHODS: Eighteen Balb/c mice (H-2K(d)) were randomized to four groups. The control group (n=5) received syngeneic limb transplants from Balb/c donors. The experimental groups were recipients of limb allografts from C57Bl/6 mice (H-2K(b)) and received either no treatment (n=5) or treatment with MR1 (hamster antimouse CD40 ligand monoclonal antibody) 500 microg intraperitoneally (IP) on days 0, 2, 4, 6, 14, 28, and 60 (n=5). A fourth group received myocutaneous allografts from C57Bl/6 donors and the same treatment with MR1 (n=5). RESULTS: Untreated limb allografts were rejected at a mean of 9.6+/-1.1 days postoperatively. MR1-treated limb allografts underwent rejection of the skin component at a mean of 75+/-25 days whereas the musculoskeletal component survived to a mean of 222+/-84 days with two allografts surviving more than 10 months (P<0.001). The MR1-treated myocutaneous allografts were rejected after 16.2+/-2 days. All groups demonstrated acute rejection on histology except the treated limb allograft group, which was more suggestive of a chronic process. No chimerism was detected in this group by flow cytometry. CONCLUSIONS: CD40 costimulatory blockade significantly prolonged limb-allograft survival, and the bone-marrow component may have played an important role. Tolerance was not achieved, and histologic evaluation suggested chronic rejection as a possible cause of allograft loss.

Animals↗
PubMed2003

Use of mixed lymphocyte reaction to identify subimmunosuppressive FK-506 levels in mice.

The immunosuppressive agent FK-506 has a well-described neuroregenerative effect that is mediated by a mechanism independent of calcineurin inhibition. FK-506 levels that fall below the threshold for immunosuppression could therefore potentially enhance nerve regeneration while minimizing toxicity. The purpose of this study was to characterize the dose-dependent effects of FK506 on T-cell proliferation, and establish a subimmunosuppressive dosing regimen for FK-506 in mice. Forty BALB/cJ mice were randomized to four groups corresponding to 0, 0.25, 0.5, or 1.0 mg/kg/day doses of FK-506. Ten days postoperatively, animals were sacrificed, and mixed lymphocyte reaction assays were performed to quantify the immune response to nerve allografts. Mice receiving 0.25 and 0.5 mg/kg/day of FK-506 exhibited a robust T-cell proliferation response, with stimulation indices approaching those of untreated animals. Mice treated with 1.0 mg/kg/day of FK-506 demonstrated significantly decreased T-cell proliferation. These results establish 0.5 mg/kg/day as an upper limit for subimmunosuppressive FK-506 administration.

Animals↗
PubMed2003

Controlled release of nerve growth factor enhances sciatic nerve regeneration.

Based on previous studies demonstrating the potential of growth factors to enhance peripheral nerve regeneration, we developed a novel growth factor delivery system to provide sustained delivery of nerve growth factor (NGF). This delivery system uses heparin to immobilize NGF and slow its diffusion from a fibrin matrix. This system has been previously shown to enhance neurite outgrowth in vitro, and in this study, we evaluated the ability of this delivery system to enhance nerve regeneration through conduits. We tested the effect of controlled NGF delivery on peripheral nerve regeneration in a 13-mm rat sciatic nerve defect. The heparin-containing delivery system was studied in combination with three doses of NGF (5, 20, or 50 ng/mL) and the results were compared with positive controls (isografts) and negative controls (fibrin alone, NGF alone, and empty conduits). Nerves were harvested at 6 weeks postoperatively for histomorphometric analysis. Axonal regeneration in the delivery system groups revealed a marked dose-dependent effect. The total number of nerve fibers at both the mid-conduit level and in the distal nerve showed no statistical difference for NGF doses at 20 and 50 ng/mL from the isograft (positive control). The results of this study demonstrate that the incorporation of a novel delivery system providing controlled release of growth factors enhances peripheral nerve regeneration and represents a significant contribution toward enhancing nerve regeneration across short nerve gaps.

Animals↗
PubMed2003

Brachial plexus injuries.

Severe trauma to the brachial plexus most often occurs in young adult men and is a crippling injury that requires management in a timely fashion for optimal functional recovery and pain control. The surgical management of such injuries is well established, and the techniques continue to evolve. Current management options consist of primary repair in the acute setting, neurolysis, neuroma resection and nerve grafting, motor and sensory nerve transfers, and muscle and tendon transfers. Shoulder andwrist fusion can also play a role in the overall management of these patients. The best operative plan varies depending on the patient's level and extent of injury and the surgeon's preference and experience. The pre- and postoperative care of these patients is ideally managed by a team that has experience with such problems, including personnel knowledgeable in their postoperative rehabilitation. The total reconstructive process generally consists of more than one operation, and the postoperative rehabilitation is long and intensive. Nevertheless, with a highly motivated patient and a dedicated and specialized surgical team, the prognosis for functional recovery is good, and these patients can still lead productive and satisfying lives.

Brachial Plexus↗
PubMed2003

Pathophysiology of nerve injury.

The response to nerve injury is a complex and often poorly understood mechanism. An in-depth and current command of the relevant neuroanatomy, classifications systems, and responses to injury and regeneration are critical to current clinical success. Continued progress must be made in our current understanding of these varied physiologic mechanisms of neuro-regeneration if any significant progress in clinical treatments or outcome is to be expected in the future. Reconstructive surgeons have in many ways maximized the technical aspects of peripheral nerve repair. However, advances in functional recovery may be seen with improvements in sensory and motor rehabilitation after peripheral nerve surgery and with a combined understanding of the neurobiology and neurophysiology of nerve injury and regeneration.

Animals↗
PubMed2003

The surgical management of facial nerve injury.

Treatment of facial nerve injuries depends upon a detailed understanding of its anatomic course, accurate clinical examination, and timely and appropriate diagnostic studies. Reconstruction depends upon the extent of injury, the availability of the proximal stump. and the time since injury and duration of muscle denervation. Although no alternative is perfect, these techniques, in combination with static and ancillary procedures. can protect the eye, prevent drooling, restore the smile, and improve facial symmetry. New techniques (including single-stage free tissue transfers and bioengineered nerve grafts), further research on the characteristics of the facial musculature, and methods of preserving the neuromuscular junction will undoubtedly manifest themselves as further refinements of established surgical techniques.

Acute Disease↗
PubMed2003

Management of neuromas.

After nerve injury and regeneration, significant pain may be associated with the scar and altered sensation observed within the distribution of the injured nerve. A bulbous swelling may form at the severed nerve end, constituting a traumatic neuroma. The development of a painful neuroma may be more disabling to the patient than an area of anesthesia or even loss of motor function. Effective treatment of the painful neuroma remains a difficult problem. Diminished productivity, alterations in patient lifestyle, and possible progression to chronic pain syndromes must be considered within the scope of neuroma management, and treatment must focus on alleviating the pain and restoring the functional loss caused by the nerve injury. Careful patient selection is the cornerstone of successful outcomes. Once the patient has been selected, the surgical management of the painful neuroma throughout the body is based on basic principles that vary only slightly from region to region. Using these tenets, a neuroma management algorithm has been developed based on the pathophysio-logy of the neuroma, the results of experimental studies, review of patient outcomes, and understanding the psychology of pain in the surgical patient.

Extremities↗
PubMed2003

Functional recovery and histomorphometric assessment following tibial nerve injury in the mouse.

Longitudinal studies have established that functional recovery following sciatic nerve injury can be evaluated in the mouse. Injury to the tibial nerve offers several advantages to sciatic nerve injury, including improved lower extremity sensation and end-organ reinnervation. Functional recovery following tibial nerve crush injury was studied in 55 C3H mice randomized into five groups harvested for histomorphometric evaluation from either normal nerves or 2, 3, 4, or 6 weeks postoperatively. Walking tracks were obtained preoperatively, and at regular intervals postoperatively, and foot print lengths measured. Significant normalization of print length occurred 14 days postoperatively, and complete recovery was noted 28 days postoperatively. Significant histomorphologic evidence of neuroregeneration was detected between 2 and 4 weeks postoperatively. Injury to the tibial nerve is a viable alternative to the sciatic nerve for studying neural regeneration in mice, and the print length factor can be used to monitor functional recovery in this model.

Animals↗
PubMed2003

Effects of delaying FK506 administration on neuroregeneration in a rodent model.

FK506 is an immunosuppressant drug that has been shown experimentally to stimulate nerve growth and speed functional recovery, when administered immediately after peripheral nerve injury. However, the clinical scenario of a peripheral nerve injury is often associated with either a delayed diagnosis or reconstruction. The purpose of this study was to determine the efficacy of FK506 on neuroregeneration with delayed administration. Thirty-two Lewis rats underwent tibial nerve transection with immediate repair. Animals were left untreated, or were treated with daily injections of FK506 (2 mg/kg), started on the day of surgery, postoperative day 3, or postoperative day 5. Animals underwent walking track analysis to assess functional nerve recovery. Nerves were harvested for histomorphometric analysis on postoperative days 21, 28, and 42. Histomorphometry demonstrated that all treatment groups, regardless of the time of drug initiation, demonstrated evidence of enhanced neuroregeneration, compared to the untreated group. Histomorphometric data from groups harvested on day 21 demonstrated a statistically significant improvement in neuroregeneration in the immediate and 3-day delay groups. Therefore, the beneficial effects of FK506 on neuroregeneration are not restricted to immediate administration, but these effects significantly diminish when FK506 is administered 3 days after nerve injury.

Animals↗
PubMed2003

Needlestick injuries among medical students.

BACKGROUND: Concern about occupational exposure to bloodborne pathogens exists, and medical students, who lack in experience in patient care and surgical technique, may be at an increased exposure risk. METHODS: This prospective cohort study evaluated needlestick injuries and practices regarding the use of protective strategies against bloodborne pathogens in medical students. A questionnaire was developed and sent to 224 medical students. RESULTS: Of 224 students, 146 students (64%) returned questionnaires. Forty-three students (30%) reported needlestick injuries that most commonly occurred in the operating room; 86% of students reported always using double gloves in the operating room; 90% reported always wearing eye protection, and all but one student had been vaccinated against hepatitis B. A concern about contracting a bloodborne pathogen through work was noted in 125 students, although they usually reported that this concern only slightly influenced their decision regarding a career subspecialty. CONCLUSION: Medical students have a high risk for needlestick injuries, and attention should be directed to protection strategies against bloodborne pathogens.

Adult↗