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Biomedical subjects

Susan E Mackinnon

Publications and source records attributed to Susan E Mackinnon.

At least 37 records · Page 2Linked to original sources
PubMed2005

Analysis of the nerve branches to the orbicularis oculi muscle of the lower eyelid in fresh cadavers.

BACKGROUND: Scleral show or ectropion is a known complication of lower eyelid surgery. It is particularly problematic after lower eyelid blepharoplasty when the orbicularis oculi muscle is transected or after other procedures are performed that denervate the lower eyelid. The purpose of this study was to determine whether a dominant motor branch exists to the lower lid orbicularis oculi muscle, using anatomic dissection and histologic analysis. METHODS: Sixteen fresh facial cadaver halves were dissected using the operative microscope to identify and measure nerve branches. The nerves were then harvested, sectioned, and stained with toluidine blue dye for histomorphometric analysis. Nerves were categorized as either lateral or medial to a vertical line marked at the lateral edge of the limbus of the eye. RESULTS: Eighty-seven percent and 47 percent of cadaver halves had one and two nerve branches lateral to the limbus, respectively. Eighty percent and 47 percent of cadaver halves had one and two nerve branches medial to the lateral limbus, respectively. The nerve branches entered the inferior edge of the orbicularis oculi muscle between 0.88 cm (+/-0.36 cm) and 2.73 cm (+/-0.46 cm) from the lateral canthus. There was no correlation noted between fascicular counts and distance from the lateral canthus. CONCLUSIONS: Multiple motor nerves exist to the lower eyelid. Branches are found medial and lateral to the lateral limbus, and no nerve branch is dominant.

Blepharoplasty↗
PubMed2005

Effect of FK506 on peripheral nerve regeneration through long grafts in inbred swine.

Numerous small-animal studies have demonstrated that FK506 enhances nerve regeneration and accelerates functional recovery after nerve injury. However, no experimental study has corroborated these neuroregenerative effects in larger animals. This study investigated the effects of FK506 on nerve regeneration in inbred miniature swine. Eight animals received 8-cm ulnar nerve autografts and allografts. Treated animals received 0.1 to 0.4 mg/kg FK506 injections twice weekly to maintain immunosuppressive serum FK506 levels. At 24 weeks posttransplant, nerve grafts were harvested for histomorphometric analysis. Mixed lymphocyte cultures demonstrated alloreactivity in 1 treated animal and all untreated animals. In autografts, mean fiber count, nerve density, and percent neural tissue were doubled with FK506 therapy. In allografts, significant neuroregeneration was observed in animals treated with FK506, whereas untreated animals had no regeneration. Treatment with FK506 resulted in a trend toward enhanced axonal regeneration through nerve autografts and allografts in a large-animal model with defined histocompatibility barriers.

Animals↗
PubMed2005

Combined treatment with CD40 costimulation blockade, T-cell depletion, low-dose irradiation, and donor bone marrow transfusion in limb allograft survival.

To determine the efficacy of a regimen based on CD40 costimulation blockade and donor bone marrow in the limb allograft model, C57Bl/6 mice received limb allografts from Balb/c mice and either no treatment or a combination of MR1 (anti-CD40 ligand monoclonal antibody), CD4+ and CD8+ T-cell-depleting antibodies, low-dose irradiation, and bone marrow transfusion from Balb/c donors for 1 or 2 weeks. Recipients treated for 1 week showed rejection at 38.2 +/- 5.4 (mean +/- SEM) days, while those treated for 2 weeks had allograft survival of 56.5 +/- 9.9, with a range up to 91 days. Histology demonstrated rejection which was less cell-mediated and suggestive of transplant vasculopathy. Differential rejection of skin occurred first. Thus, a combined regimen based on CD40 costimulatory blockade and donor marrow significantly prolonged allograft survival. However, tolerance was not achieved, and histology suggests chronic rejection as a possible cause of allograft loss.

Animals↗
PubMed2005

Nerve reconstruction in lumbosacral plexopathy. Case report and review of the literature.

Neurological injury to the lumbosacral plexus associated with pelvic and sacral fractures has traditionally been treated conservatively, despite significant and often debilitating functional deficits of the lower extremities. The authors report a case of reconstruction of the lumbosacral plexus, including nerve grafting to restore lower-extremity function caused by severe trauma to the pelvis. A 16-year-old boy sustained pelvic and sacral fractures in a motor vehicle accident. After stabilization of his orthopedic injuries, he suffered from paresis of his right gluteal and hamstring muscles and had no motor or sensory function below his knee. Two months later, he underwent reconstruction of his lumbosacral plexus performed using a nerve graft from his L-5 and S-1 nerve roots proximal to the inferior gluteal nerve and distal to a branch to the hamstring muscles. After another 2 months, his recovering saphenous nerve was transferred to the sensory component of the posterior tibial nerve by using cabled sural nerve grafts to restore sensation to the sole of his foot. After 2.5 years, he experienced reinnervation of his gluteal and hamstring muscles and could perceive vibration on the sole of his foot. With the assistance of a foot-drop splint, the patient ambulates well and is able to ski. Operative details and the relevant literature are reviewed.

Accidents, Traffic↗
PubMed2005

FK506 and anti-CD40 ligand in peripheral nerve allotransplantation.

PURPOSE: Immunomodulatory agents are often combined in organ transplantation to minimize toxicity and enhance therapeutic effect. We hypothesized that combining low-dose FK506 with anti-CD40 Ligand (anti-CD40L mAb) would enhance regeneration through peripheral nerve allografts while preserving immune unresponsiveness. METHODS: Eighty Balb/cJ mice underwent tibial nerve grafting and were randomized to 10 groups treated with combinations of anti-CD40L mAb therapy, low-dose FK506 (0.5 mg/kg/day), high-dose FK506 (2 mg/kg/day), and high-dose cyclosporine (25 mg/kg/day). At 3 weeks, histomorphometry and cytokine secretion assays were performed. RESULTS: Animals receiving low-dose FK506 with anti-CD40L mAb exhibited robust nerve regeneration comparable to the isograft and high-dose FK506 allograft groups. Nerve density was significantly increased in the low-dose FK506 with anti-CD40L mAb group compared to animals receiving anti-CD40L mAb alone (p < 0.05). Combining anti-CD40L mAb with high dose cyclosporine decreased nerve fiber counts, nerve density, and percent nerve (p < 0.05). Interferon-gamma production was markedly elevated in untreated allografts compared to all other treatment groups (p < 0.05). Cytokine secretion was intermediate in the low-dose FK506 alone group and suppressed in all remaining groups. CONCLUSION: When combined with anti-CD40L mAb, low-dose FK506 enhances nerve regeneration without disrupting immune unresponsiveness.

Animals↗
PubMed2004

The position of crossing branches of the medial antebrachial cutaneous nerve during cubital tunnel surgery in humans.

The posterior branch of the medial antebrachial cutaneous nerve courses in proximity to the cubital tunnel and is particularly prone to injury during ulnar nerve release at the elbow. Inadvertent injury to medial antebrachial cutaneous nerve branches during surgery can result in the formation of painful neuromas that can be misdiagnosed as recurrent disease. It is important to understand the relevant anatomy of the medial antebrachial cutaneous nerve branches during cubital tunnel surgery to avoid significant postoperative morbidity. This prospective observational anatomic study examined the position of the posterior branch of the medial antebrachial cutaneous nerve in relationship to a standard approach to the cubital tunnel in a randomly selected group of 97 patients undergoing primary surgery over a 3-year period. Medial antebrachial cutaneous nerve branches were noted to cross at or proximal to the medial humeral epicondyle 61 percent of the time at an average proximal distance of 1.8 cm. Medial antebrachial cutaneous nerve branches were noted to cross distal to the medial humeral epicondyle 100 percent of the time at an average distal distance of 3.1 cm. Understanding the general position of crossing medial antebrachial cutaneous nerve branches during ulnar nerve release at the elbow may help to prevent iatrogenic injury to this cutaneous nerve.

Adolescent↗
PubMed2004

The gender gap in a surgical subspecialty: analysis of career and lifestyle factors.

BACKGROUND: Although the percentage of women in surgical subspecialties is increasing, little is known about the experiences of these women compared with their male counterparts. OBJECTIVE: To identify career and lifestyle factors that distinguish female otolaryngologists. DESIGN, SETTING, AND PARTICIPANTS: Otolaryngologists were asked to respond to a confidential 119-item questionnaire. The instrument was sent to all 502 female members of the American Academy of Otolaryngology-Head and Neck Surgery who had finished their residency training and were practicing medicine. For response comparison, the survey was mailed to 2 male otolaryngologists who were matched to each female survey recipient for years since completion of training, geographic region, and practice type. RESULTS: Of the 673 respondents (52.6% response rate), women were more likely to be divorced or separated (P =.001) and have fewer children (P <.001). In contrast to men, women reduced their work hours in conjunction with having more children (P <.001). Controlling for professional hours and hours spent in the operating room per week, type of practice, and years since completion of residency, women earned 15% to 20% less per year than men (P <.001). Men relied more on their spouse or partner for household responsibilities and child care (P <.001), and 34.3% of the women (compared with 7.1% of the men) spent 21 to 40 h/wk on household management (P <.001). CONCLUSION: Although male and female otolaryngologists receive equal training opportunities, women earn less money for performing similar jobs and have increased family responsibilities, which may effect their career advancement.

Adult↗
PubMed2004

Use of anti-CD40 ligand monoclonal antibody as antirejection therapy in a murine peripheral nerve allograft model.

Monoclonal antibody directed against CD40 ligand prevents acute allograft rejection in several models of solid-organ transplantation. This study describes the use of CD40 ligand as antirejection therapy in a mouse peripheral nerve allograft model. C3H mice received 8-mm nerve isografts (n = 2) or nerve allografts from C57BL donors. Treated animals (n = 11) received anti-CD40 ligand antibody applied to the graft and by intraperitoneal injections postoperatively. At 3 weeks, nerve histology from treated animals was comparable to isografts, whereas untreated allografts demonstrated virtually no signs of regeneration. Walking-track analysis demonstrated a trend toward improved functional recovery in treated animals. In conclusion, blockade of the CD40 pathway suppresses nerve allograft rejection in mice, and facilitates regeneration comparable to isografts.

Animals↗
PubMed2004

Anti-CD40 ligand monoclonal antibody induces a permissive state, but not tolerance, for murine peripheral nerve allografts.

Anti-CD40 ligand monoclonal antibody prevents the interaction between CD40 and its T-cell-based ligand, thereby resulting in selective inhibition of T cell costimulation without pan-T-cell suppression. This antibody has found application in several animal models of solid organ transplantation. This study investigated use of anti-CD40 ligand antibody to promote acceptance of nerve allografts. In Experiment 1, 40 BALB/cj mice with tibial nerve transplants were administered anti-CD40 ligand antibody, a control antibody, or no treatment. In Experiment 2, 40 BALB/cj mice underwent the same regimen as in Experiment 1, but were later challenged with a second nerve allograft 3 weeks after discontinuation of treatment. Animals treated with anti-CD40 ligand antibody in Experiment 1 exhibited improved functional recovery and greater mean fiber count, fiber density, and percent nerve fiber than animals treated with control antibody or no antibody (P < 0.05). These permissive effects on nerve regeneration were associated with immune unresponsiveness on Elispot assay. The benefit of anti-CD40 ligand therapy did not persist after withdrawal of treatment (Experiment 2). Active blockade of the CD40 costimulatory pathway with murine anti-CD40 ligand antibody therefore induces a permissive state conducive to nerve regeneration across allografts but does not establish long-term tolerance.

Animals↗
PubMed2004

Effects of motor versus sensory nerve grafts on peripheral nerve regeneration.

Autologous nerve grafting is the current standard of care for nerve injuries resulting in a nerve gap. This treatment requires the use of sensory grafts to reconstruct motor defects, but the consequences of mismatches between graft and native nerve are unknown. Motor pathways have been shown to preferentially support motoneuron regeneration. Functional outcome of motor nerve reconstruction depends on the magnitude, rate, and precision of end organ reinnervation. This study examined the role of pathway type on regeneration across a mixed nerve defect. Thirty-six Lewis rats underwent tibial nerve transection and received isogeneic motor, sensory or mixed nerve grafts. Histomorphometry of the regenerating nerves at 3 weeks demonstrated robust nerve regeneration through both motor and mixed nerve grafts. In contrast, poor nerve regeneration was seen through sensory nerve grafts, with significantly decreased nerve fiber count, percent nerve, and nerve density when compared with mixed and motor groups (P < 0.05). These data suggest that use of motor or mixed nerve grafts, rather than sensory nerve grafts, will optimize regeneration across mixed nerve defects.

Animals↗
PubMed2004

Stem cell transplantation and other novel techniques for promoting recovery from spinal cord injury.

A number of potential approaches aim to optimize functional recovery after spinal cord injury. They include minimizing the progression of secondary injury, manipulating the neuroinhibitory environment of the spinal cord, replacing lost tissue with transplanted cells or peripheral nerve grafts, remyelinating denuded axons, and maximizing the intrinsic regenerative potential of endogenous progenitor cells. We review the application of stem cell transplantation to the spinal cord, emphasizing the use of embryonic stem cells for remyelinating damaged axons. We speculate that harnessing the potential of endogenously born stem cells already present in the spinal cord represents an important therapeutic target. We also discuss the potential application of peripheral nervous system reconstruction to recovery from spinal cord injury. The principles of peripheral nerve regeneration and concepts of nerve grafting are reviewed. Particular attention is given to peripheral nerve allotransplantation for repairing extensively injured tissue when autologous donor nerve material is scarce. The potential role of nerve transfers for reconstructing the injured spinal cord, particularly the cauda equina and lumbosacral plexus, are also described.

Animals↗
PubMed2004

Distal anterior interosseous nerve in the recurrent motor branch graft for reconstruction of a median nerve neuroma-in-continuity.

Median nerves with neuromas-in-continuity are preferably managed by the identification and preservation of the functioning motor fascicles proximal and distal to the neuroma. The non-functioning, painful sensory fibers are divided proximally and distally and are reconstructed with nerve grafts. In cases where the proximal motor fascicle may not be safely and effectively isolated because of scarring or previous surgical intervention, the distal anterior interosseous nerve (dAIN) may be grafted to the recurrent motor branch of the median (RMB) nerve distal to the neuroma. The primarily motor fibers of the dAIN provide an expendable donor of adequate size and fascicle number to restore thenar muscle function.

Adult↗
PubMed2004

Immune unresponsiveness by intraportal UV-B-irradiated donor antigen administration requires persistence of donor antigen in a nerve allograft model.

The purpose of this study was to characterize the mechanism of unresponsiveness produced by the intraportal administration of ultraviolet-B (UV-B)-irradiated donor antigen. Pretreated Buffalo rats accepted Lewis nerve allografts, had decreased in vitro T-cell reactivity, and demonstrated nerve regeneration and recovery of limb function, while rejecting third-party nerve allografts. Regenerated nerve grafts were then retransplanted into a second naïve recipient. Rejection of the retransplanted allograft by naïve donor-strain, but not recipient-strain, animals suggests that the allografts were completely replaced by host tissue. Pretreated Buffalo rats were also given a second Lewis allograft after the first had regenerated. The second allograft was rejected and in vitro immune reactivity was comparable to naïve animals. Because the unresponsiveness state was extinguished with loss of exposure to donor antigen, these findings suggest that the intraportal administration of UV-B-irradiated donor antigen works by anergic or suppressive regulatory, rather than deletional, mechanisms.

Animals↗
PubMed2004

A novel model for the study of peripheral-nerve regeneration following common nerve injury paradigms.

Recent advances in molecular neurobiology include the development of transgenic mice that express genes encoding fluorescent proteins under neuron-specific promoters (XFP mice). These mice have been used in the field of developmental neurobiology, but use has expanded to include the study of peripheral-nerve axonal regeneration subsequent to crush or unrepaired transection injuries. This report presents a transgenic mouse, which differs from previously reported and commercially available mice, in that enhanced yellow fluorescent protein expression (EYFP) is driven by the human thy1 promoter (hThy1). Motor and sensory peripheral nerves in these mice appear a bright yellow-green under fluorescent microscopy. This study tracks nerve regeneration in live animals using a serial imaging system. It also introduces a novel model for examining the clinically relevant nerve-injury paradigms of tibial nerve transection repaired with primary neurorrhaphy or graft, and end-to-side neurorrhaphy. Live-animal serial nerve imaging is compared with wet-mount fluorescent microscopy and histomorphometry in the same nerve specimens. The use of transgenic mice that strongly express EYFP in their peripheral neurons, coupled with serial nerve imaging, provide an important methodology for studying the heterogeneous nature of axonal elongation following peripheral-nerve injuries.

Animals↗
PubMed2004

Effect of perineurial window size on nerve regeneration, blood-nerve barrier integrity, and functional recovery.

End-to-side neurorrhaphy is used clinically to reconstruct nerve injuries when the lack of a suitable proximal nerve stump precludes conventional approaches to microsurgical repair. In end-to-side neurorrhaphy, the distal stump of a transected nerve is sutured to the side of an intact nerve that serves as an axon donor. Prior studies suggest that this perineurial window is a prerequisite for effective nerve regeneration into the recipient nerve. However, the optimal size for this perineurial window remains uncertain. This study evaluated the effect of perineurial window size on collateral axonal sprouting, blood-nerve barrier architecture, and functional impairment of the donor nerve. One hundred twenty Lewis rats were randomized to 1 and 5 mm perineurial window groups and examined at serial time points. The 5 mm perineurial window group exhibited significantly greater fiber counts at the repair zone than the 1mm group within 4 weeks (p < 0.005). Marked breakdown of the blood-nerve barrier was present 2 week postoperatively and resolved by 4 weeks regardless of 1 versus 5 mm perineurial window size. Tibial function indices in both groups normalized between 4 and 6 weeks postoperatively. A large (5 mm) perineurial window induced greater collateral sprouting or regenerative response than a small (1 mm) perineurial window without increasing cross sectional nerve injury or delaying functional recovery.

Animals↗
PubMed2004

Delayed nerve repair is associated with diminished neuroenhancement by FK506.

OBJECTIVES/HYPOTHESIS: The immunosuppressive agent FK506 has been shown in many studies to enhance nerve regeneration and to accelerate functional recovery after immediate nerve repair. However, in clinical practice the diagnosis and treatment of patients with peripheral nerve injuries is often delayed. The study investigated whether FK506 would retain its neuroregenerative properties when nerve repair and initiation of FK506 therapy were delayed for 7 days. STUDY DESIGN: In vivo laboratory study. METHODS: Thirty-two Lewis rats underwent tibial nerve transection and were randomly assigned to four experimental groups: immediate repair with FK506 treatment, immediate repair without FK506 treatment, 7-day delayed repair with FK506 treatment, and 7-day delayed repair without FK506 treatment. Treated animals received daily subcutaneous injections of 2 mg/kg FK506. Serial walking track measurements were performed at 14, 16, and 18 days after nerve repair. On day 18 after repair, peripheral nerves were injected with a fluorescent tracer for retrograde labeling. On day 21, peripheral nerves and spinal cords were harvested for histomorphometric analysis and motor neuron cell body counts, respectively. RESULTS: Animals that underwent immediate repair with FK506 had significantly higher fiber counts and percentages of nerve than the other three groups (P <.05) but did not show statistically significant earlier functional recovery. The remaining three groups had intermediate levels of nerve regeneration that were not significantly different. Retrograde abled motor neurons counts were decreased in animals with delayed nerve repair that received no FK506 (P <.05). CONCLUSION: In a rat tibial nerve transection model, the neuroregenerative effects of FK506 diminished markedly when repair and initiation of FK506 therapy were delayed by 7 days.

Analysis of Variance↗
PubMed2004

Effects of external beam radiation in the rat tibial nerve after crush, transection and repair, or nerve isograft paradigms.

INTRODUCTION: In head and neck surgery, radiation therapy is often administered to an injured nerve. Previous studies have examined the effects of either preoperative or postoperative radiation on nerve regeneration in rodents. In these studies, histomorphometric analysis was performed up to 8 month postoperatively. Given the exceptional neuroregenerative capacity of rodents, significant differences in nerve regeneration may go undetected if nerves are evaluated at such distant postoperative time points. This study is designed with a more appropriate model and investigates the effects of radiation after three common nerve injury paradigms. METHODS: Sixty-four Lewis rates were randomized to 8 groups corresponding to uninjured, tibial nerve crush, transection and repair, or reconstruction with isografts. Half of the animals in each of these paradigms (n = 8 per group) were treated with 10 Gy of external beam radiation to the site of nerve injury at 7 days postoperatively. On postoperative day 28, functional recovery and histomorphometric assessment was performed. RESULTS: For a given paradigm of nerve injury, no significant differences in nerve fiber number, neural density, neural debris, or fiber width were noted between the control and radiated groups, and radiation did not affect functional recovery. CONCLUSION: Radiation had no discernible effect on nerve regeneration or functional recovery in the rodent nerve injury models studied. All assessments were made at time points suitable for detecting differences in nerve regeneration between groups. These findings suggest that administration of radiation to fields containing injured peripheral nerve is unlikely to adversely affect functional outcomes.

Animals↗