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Galphaq-coupled receptors such as alpha1-adrenergic, angiotensin, and endothelin receptors, play key roles in cardiac physiology. These receptors have also been shown to couple to G proteins of the G12 family, including Galpha12 and Galpha13. In this report, we determined whether these G proteins interact with endothelin, angiotensin, and alpha1-adrenergic receptors in the human heart. We find that these receptors activate cardiac Galpha12 and Galpha13 differentially; endothelin receptors activate only Galpha12 (to 218 +/- 22% of unstimulated levels), angiotensin receptors activate only Galpha13 (to 236 +/- 49% of unstimulated levels), and alpha1-adrenergic receptors activate neither Galpha12 (123 +/- 18% of unstimulated levels) nor Galpha13 (113 +/- 12% of unstimulated levels). Consistent with these data, translocation of guanine nucleotide exchange factor p115RhoGEF, which responds to Galpha13, occurs only after stimulation of angiotensin receptors (shifting from 73 +/- 12% to 41 +/- 10% cytosolic). These differences in the activation of Galpha12 and Galpha13 by Galphaq-coupled receptors may underlie reported differences in the functions of these receptors.

Background: Prostate cancer is the second most common cause of cancer deaths in men in the United States. Many patients experience partial or complete loss of erectile function following prostatectomy. The cavernous nerves can be reconstructed intraoperatively using sural nerve grafts in an attempt to restore erectile function., Methods: In this study, multiple anatomical dissections and neurologic assessments were used to define the position and histologic parameters of the cavernous nerve in a canine model. The subsequent experimental design included three groups of adult mongrel dogs followed for an 8-month period. Group 1, the control group, underwent bilateral nerve ablation to substantiate surgically induced loss of erectile function. Group 2, the "sham" group, underwent exploration only. Group 3 underwent bilateral cavernous nerve ablation with bilateral sural nerve graft reconstruction. Erectile function was evaluated with indirect electrical nerve and manual penile stimulation preoperatively and 1, 2, 4, 6, and 8 months postoperatively. Direct nerve stimulation and histologic analysis was preformed at the first operation and at the time the animals were euthanized at 8 months., Results: Bilateral cavernous nerve ablation resulted in a significant loss of erectile function for 8 months postoperatively in the control animals. The sham animals demonstrated preservation of erectile function immediately following exploration. The animals in the grafted group demonstrated a significant return of erectile function by 4 months compared with preoperative measurements and by 2 months compared with control animals., Conclusions: This study establishes the first large-animal model for surgically induced loss of erectile function with successful cavernous nerve graft reconstruction, and it provides the unique opportunity to explore the effects of changes to this model in the future.

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.

Nerve allotransplantation provides a limitless source of nerve graft material for the reconstruction of large neural defects. It does require systemic immunosuppression or induction of immune unresponsiveness to prevent allograft rejection. It is unknown whether a greater volume of nerve graft material will increase the risk of rejection or the need for more intensive immunosuppression. This study assessed the relationship between the quantity of nerve tissue transplanted and the magnitude of the resulting immune response. Forty female (BALB/c) mice were randomly assigned to two groups that received either nerve isografts (BALB/c) or nerve allografts (C57BL/6). Each group was then subdivided into two groups that received either one or 10 sciatic nerve graft inlays. Histological and immunological assessments were performed at 10 days after engraftment. Histologic analysis demonstrated greater cellular infiltration in the allograft than the isograft groups but no appreciable difference in infiltration related to quantity of transplanted nerve tissue. In vitro assessments of the immune response using mixed lymphocyte assays and limiting dilution analysis similarly demonstrated a robust immune response to allografts but no effect on quantity of transplanted nerve tissue. These data suggest that larger peripheral nerve allografts may not be subject to increased risk for rejection.

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.

This study explored the effects of different doses of FK506 on peripheral nerve regeneration, to determine whether neuroregeneration could be enhanced without the toxicity of systemic immunosuppression. In the first part of the study, subimmunosuppressive doses of FK506 were determined by examining skin allograft survival in a rat model. Full-thickness skin grafts (2 cm2) from Wistar rats were grafted to recipient Lewis rats. The procedure was performed for six groups (n = 6). The control group received no FK506, and the other five groups received daily doses of FK506 of 0.125, 0.25, 0.5, 1.0, or 2.0 mg/kg. Animals that received 2.0 mg/kg FK506 per day exhibited complete skin graft take, whereas all other groups demonstrated complete rejection. After determination of the immunosuppressive dose of FK506, the neuroregenerative effects of different doses of FK506 were explored by assessing nerve regeneration in 80 rats after tibial nerve transection and repair. The control group received no FK506, whereas the other four groups were given daily doses of FK506 of 0.25, 0.5, 1.0, or 2.0 mg/kg. Rats were euthanized at three time points (25, 30, and 35 days), to fully investigate the effects of different FK506 dosing regimens on neuroregeneration. Histomorphometric analyses performed on postoperative days 30 and 35 demonstrated statistically significant improvements in neuroregeneration with subimmunosuppressive FK506 doses of 0.5 and 1.0 mg/kg per day. Therefore, the study demonstrated that neuroregeneration was enhanced at low doses of FK506 that were not sufficient to prevent skin allograft rejection.

The reconstruction of complex abdominal wall defects can often pose a significant challenge to surgeons and their patients. Complex ventral hernias may result from large tumor resections, trauma from gunshot wounds, or infections following routine abdominal surgery. "Components separation" of the abdominal musculature uses advancement of local autologous tissue, when available, to close large ventral wall defects. The authors report on a retrospective chart review of 30 patients who underwent components separation for the closure of complex abdominal defects. The study group was 50 percent female, with a mean age of 45 years, body mass index of 33.2 kg/m2, and abdominal defect size of 240 cm2. On average, 20 percent of patients had preoperative wound infections, 30 percent had intraoperative bowel enterotomies, and 33 percent required prosthetic mesh for closure. Total surgery time averaged 4.8 hours, with a mean postoperative stay of 12.5 days and follow-up of 9.5 months. The recurrence rate was 10 percent; postoperative complications included midline ischemia, infection, and dehiscence occurring at rates of 20, 40, and 43 percent, respectively. This study provides a comprehensive review of the risks and complications associated with the treatment of complex ventral hernias and those associated with abdominal "components separation."

Learning Objectives: After studying this article, the participant should be able to: 1. Identify all potential points of radial nerve compression and other likely causes of radial nerve injury. 2. Accurately diagnose both surgical and nonsurgical causes of radial nerve paralysis. 3. Define a safe and effective approach to the surgical release and reconstruction of the radial nerve. Radial nerve paralysis, which can result from a complex humerus fracture, direct nerve trauma, compressive neuropathies, neuritis, or (rarely) from malignant tumor formation, has been reported throughout the literature, with some controversy regarding its diagnosis and management. The appropriate management of any radial nerve palsy depends primarily on an accurate determination of its cause, severity, duration, and level of involvement. The radial nerve can be injured as proximally as the brachial plexus or as distally as the posterior interosseous or radial sensory nerve. This article reviews the etiology, prognosis, and various treatments available for radial nerve paralysis. It also provides a new classification system and treatment algorithm to assist in the management of patients with radial nerve palsies, and it offers a simple, five-step approach to radial nerve release in the forearm.

The FKBP-12-binding ligand FK506 has been successfully used to stimulate nerve regeneration and prevent the rejection of peripheral nerve allografts. The immunosuppressant rapamycin, another FKBP-12-binding ligand, stimulates axonal regeneration in vitro, but its influence on nerve regeneration in peripheral nerve isografts or allografts has not been studied. Sixty female inbred BALB/cJ mice were randomized into six tibial nerve transplant groups, including three isograft and three allograft (C57BL/6J) groups. Grafts were left untreated (groups I and II), treated with FK506 (groups III and IV), or treated with rapamycin (groups V and VI). Nerve regeneration was quantified in terms of histomorphometry and functional recovery, and immunosuppression was confirmed with mixed lymphocyte reactivity assays. Animals treated with FK506 and rapamycin were immunosuppressed and demonstrated significantly less immune cell proliferation relative to untreated recipient animals. Although every animal demonstrated some functional recovery during the study, animals receiving an untreated peripheral nerve allograft were slowest to recover. Isografts treated with FK506 but not rapamycin demonstrated significantly increased nerve regeneration. Nerve allografts in animals treated with FK506, and to a lesser extent rapamycin, however, both demonstrated significantly more nerve regeneration and increased nerve fiber widths relative to untreated controls. The authors suggest that rapamycin can facilitate regeneration through peripheral nerve allografts, but it is not a neuroregenerative agent in this in vivo model. Nerve regeneration in FK506-treated peripheral nerve isografts and allografts was superior to that found in rapamycin-treated animals. Rapamycin may have a role in the treatment of peripheral nerve allografts when used in combination with other medications, or in the setting of renal failure that often precludes the use of calcineurin inhibitors such as FK506.