Initial observations on using magnesium metal in peripheral nerve repair.

Biodegradable magnesium metal filaments placed inside biodegradable nerve conduits might provide the physical guidance support needed to improve the rate and extent of regeneration of peripheral nerves across injury gaps. In this study, we examined basic issues of magnesium metal resorption and biocompatibility by repairing sub-critical size gap injuries (6 mm) in one sciatic nerve of 24 adult male Lewis rats. Separated nerve stumps were connected with poly(caprolactone) nerve conduits, with and without magnesium filaments (0.25 mm diameter, 10 mm length), with two different conduit filler substances (saline and keratin hydrogel). At 6 weeks after implantation, magnesium degradation was examined by micro-computed tomography and histological analyses. Magnesium degradation was significantly greater when the conduits were filled with an acidic keratin hydrogel than with saline (p < 0.05). But magnesium filaments in some animals remained intact for 6 weeks. Using histological and immunocytochemical analyses, good biocompatibility of the magnesium implants was observed at 6 weeks, as shown by good development of regenerating nerve mini-fascicles and only mild inflammation in tissues even after complete degradation of the magnesium. Nerve regeneration was not interrupted by complete magnesium degradation. An initial functional evaluation, determination of size recovery of the gastrocnemius muscle, showed a slight improvement due to magnesium with the saline but not the keratin filler, compared with respective control conduits without magnesium. These results suggest that magnesium filament implants have the potential to improve repair of injured peripheral nerve defects in this rodent model.

A new era of discovery in facial plastic surgery.

OBJECTIVE: To review recent advances in our understanding of molecular biology and wound healing relevant to facial plastic surgery. DATA SOURCES: Recent basic science literature relevant to molecular biology and wound healing and its clinical implications. CONCLUSIONS: During the 21st century, we will experience a new biological and informational age that will have profound implications for facial plastic surgery. This modern era will be driven by discoveries in molecular biology and wound healing that will result in new diagnosis and treatment modalities.

The effects of conjugated deferoxamine in porcine skin flaps.

BACKGROUND: The free radical scavenger, deferoxamine (DFO) has been shown to reduce skin flap necrosis; however, its shortcomings are its toxicity and short plasma half-life. METHODS: This study investigates the effects of the less toxic, longer acting conjugated form, DFO-Hespan (DFO-H), to ischemic porcine skin flaps. During the study, DFO-H plasma concentrations and flap viability were evaluated over 10 days. RESULTS: Steady DFO serum levels were maintained with no evidence of systemic side effects. However, DFO-H was not effective in increasing porcine skin flap viability. Mean treated flap viability (n = 18) was 36.2% +/- 1.7% (mean +/- SE ) vs control (n = 16) 35.8% +/- 2.6%, p =.9. CONCLUSION: DFO-H conjugation increases its half-life and its systemic tolerance for DFO. However, this conjugation may also reduce DFO's effectiveness to preserve flap survival probably by decreasing its ability to reach the intracellular oxygen free radicals. In addition, further studies are needed to investigate whether longer DFO administration given postoperatively can be more effective in reducing ischemic injury.

Vascular and epidermal effects of fibroblast growth factor on irradiated and nonirradiated skin flaps.

Head and neck cancer surgeons are often faced with the challenge of managing previously irradiated soft tissue that has poor vascularity and slower epithelialization. This study investigates the effect of supplemental basic fibroblast growth factor (bFGF) on flap vascularity, tissue oxygenation, and epidermal regeneration in nonirradiated (n = 40) and irradiated porcine skin flaps (n = 40). Supplemental bFGF increased vascularity in nonirradiated flaps by 80% (p = .005), with a trend to a higher tissue oxygen level by day 14. The irradiated bFGF-treated flaps did not show increased vascularity or higher tissue oxygen levels 2 weeks after surgery. However, in both irradiated and nonirradiated groups, epidermal regeneration increased by greater than 70% with supplemental bFGF (p < .002). The results of this study suggest that supplemental bFGF can increase tissue vascularity in nonirradiated tissues and epidermal regeneration in both nonirradiated and irradiated conditions.

Choosing the optimal wound dressing for irradiated soft tissue wounds.

This article reviews the healing state of the previously irradiated wound, the tenets for optimal wound care, and the choices of wound dressings now available for its management. The goal in assisting a previously irradiated surgical wound to heal is to transform its chronic wound state into an acute wound state. This transformation encourages wound healing to proceed. Six major moisture-retentive dressing categories exist to optimize its healing. They are classified into the alginates, foams, gauzes, hydrogels, hydrocolloids, and transparent films. Optimal wound care management for previously irradiated wounds involves (1) adequately debriding and cleansing the local wound, (2) accurately assessing the wound, (3) choosing the appropriate dressing based on the wound assessment, and (4) encouraging granulation tissue formation and reepithelialization.

Thyroid gland hematoma after blunt cervical trauma.

Thyroid hematoma is a rare cause of airway obstruction in victims of blunt trauma. The case of a 34-year-old woman who developed orthopnea after a low-energy motor vehicle accident is described. Presenting greater than 24 hours after her accident, the patient noted dysphagia, tracheal deviation, and postural dyspnea. The diagnosis of thyroid gland hematoma was made with a combination of fiberoptic laryngoscopy, cervical computed tomography, and great vessel and carotid angiography. Invasive airway management was not required. The patient underwent a total thyroidectomy and recovered without complications.

Effects of angiogenic growth factors and a penetrance enhancer on composite grafts.

Skin-cartilage composite grafts are invaluable tissues used in facial reconstruction, yet their survival is unpredictable beyond a 1-cm diameter. In this study, the angiogenic growth factors basic fibroblast growth factor (bFGF) and endothelial cell growth factor (ECGF) and a penetrance enhancer (dimethyl sulfoxide [DMSO]) were applied to composite grafts to determine their effects on survival and vascularization. We applied ECGF, bFGF, and DMSO either topically or by intradermal injection to 120 auricular composite grafts (3.0 cm diameter) in New Zealand White rabbits. Dermabrasion was performed in 2 groups to attempt to increase transdermal delivery. Graft viability and vascularity were evaluated 3 weeks later by template analysis and angiography. In the results, ECGF and bFGF, when grouped together, had a 40% increase in vascular ingrowth as compared to controls (p < .001). However, neither ECGF nor bFGF increased graft survival. A coincidental finding was that DMSO with dermabrasion significantly improved graft viability (>100%) with or without an angiogenic agent (p < .02). The potential of DMSO with dermabrasion to increase composite graft viability warrants further investigation.

Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG.

GATA transcription factors are required for the differentiation of diverse cell types in several species. Recent evidence suggests that their biologic activities may be modulated through interaction with multitype zinc finger proteins, such as Friend of GATA-1 (FOG) and U-shaped (Ush). In cell culture, FOG cooperates with the hematopoietic transcription factor GATA-1 to promote erythroid and megakaryocytic differentiation. We show here that mice lacking FOG die during mid-embryonic development with severe anemia. FOG-/- erythroid cells display a marked, but partial, blockage of maturation, reminiscent of GATA-1- erythroid precursors. In contrast to GATA-1 deficiency, however, megakaryocytes fail to develop in the absence of FOG. Although the FOG-/- erythroid phenotype supports the proposed role of FOG as a GATA-1 cofactor in vivo, the latter finding points to a pivotal, GATA-1-independent requirement for FOG in megakaryocyte development from the bipotential erythroid/megakaryocytic progenitor. We speculate that FOG and other FOG-like proteins serve as complex cofactors that act through both GATA-dependent and GATA-independent mechanisms.

Effects of basic fibroblast growth factor on irradiated porcine skin flaps.

OBJECTIVE: To determine the vascular and collagen effects of supplemental basic fibroblast growth factor (bFGF) in irradiated porcine skin flaps. INTERVENTION: Animals were subjected to 2 fractions of 650 cGy orthovoltage radiation. Following this, the skin flaps were administered bFGF intracuticularly for 6 days before and after surgery. The animals were sacrificed 3 weeks after the start of bFGF administration. Tissues were analyzed for vascularity, collagen content, wound-breaking strength, and histopathological analysis. RESULTS: The bFGF-treated flaps showed a 62% increase in vascularity compared with controls (10.4%+/-2.4% vs 6.43%+/-2.27%; P<.05). The bFGF flaps had a significantly lower collagen concentration compared with control flaps when measured by hydroxyproline content (0.0619+/-0.0211 nm/microg vs 0.0784+/-0.0150 nm/microg). Wound-breaking strength was not significantly different, although the bFGF flaps had a trend toward lower breaking strength. Histologically, the bFGF-treated flaps showed increased cellularity, fibroblasts, and extracellular mucopolysaccharides compared with controls. CONCLUSIONS: This study provides evidence that supplemental bFGF can increase vascularity to skin flaps in previously irradiated porcine skin tissue. Histologically, radiation did not prevent the angiogenic effect of bFGF.

Treatment of chronic tympanic-membrane perforations with a platelet-derived releasate.

PURPOSE: Tympanic membrane perforations are very common and often require surgical treatment. Recent studies have suggested that growth factors may be an effective nonsurgical alternative for treating chronic perforations. The purpose of this study was to assess the efficacy of a platelet releasate in the treatment of chronic nonhealing perforations in the chinchilla model. METHODS: Bilateral perforations were created in 47 chinchillas by excising 80% of the tympanic membrane with a thermal myringotomy knife. Bilateral perforations > 50% of its surface area persisted for 10 weeks in 34 animals, and unilateral perforations > 50% of its surface area, in nine animals. Only animals with bilateral chronic perforations were included in this study. After deepithelializing the perforation and packing the middle ear and external ear canals with Gelfoam, we treated the perforations with either platelet releasate or buffered saline. Each animal served as its own control. RESULTS: The tympanic membranes were evaluated over a 12-week period by microscopy, photography, tympanometry, and histology. No statistical difference between treated and control ears in the incidence of perforation closure was evident. Histologically, the treated tympanic membranes consistently had a thicker fibrous layer than the controls. CONCLUSIONS: These data suggest that platelet releasate is not effective in enhancing closure of chronic tympanic membrane perforations in the chinchilla model.

Vascular effects of sustained-release fibroblast growth factors.

Since the half-life of most angiogenic growth factors is several hours or less, sustained-release delivery would be optimal for their future clinical use. Two fibroblast growth factors, basic fibroblast growth factor (bFGF) and endothelial cell growth factor (ECGF), were delivered in two sustained-released modalities (poloxamer 407 and a gelatin sponge [Gelfoam]) to attempt to increase soft tissue vascularity. In vitro bioactivity of ECGF-poloxamer formulations was also tested on endothelial cell cultures. Among vascular-compromised skin flaps in rabbits, ECGF-poloxamer (N = 26), bFGF-poloxamer (N = 5), ECGF-poloxamer (N = 9, irradiated), and bFGF-Gelfoam flaps (N = 22) did not demonstrate significant differences in viability and vascularity compared to controls (p > .05). Irradiation had a detrimental effect on both flap vascularity and viability (p = .02). Future efforts for sustained delivery of angiogenic proteins are critical in order to make them clinically useful in wound healing.

The ksr-1 gene encodes a novel protein kinase involved in Ras-mediated signaling in C. elegans.

By screening for mutations that suppress the vulval defects caused by a constitutively active let-60 ras gene, we identified six loss-of-function alleles of ksr-1, a novel C. elegans gene. Our genetic analysis showed ksr-1 positively mediates Ras signaling and functions downstream of or in parallel to let-60. In the absence of ksr-1 function, normal Ras signaling is impaired only slightly, suggesting ksr-1 may act to modulate, or in a branch that diverges from, the main signaling pathway. The predicted KSR-1 protein has a protein kinase domain and is most similar to a recently identified Drosophila protein involved in Ras signaling. We propose that the function of ksr-1 is evolutionarily conserved.

Microcystic adnexal carcinoma: management options based on long-term follow-up.

Microcystic adnexal carcinoma (MAC), a recently described neoplasm that frequently affects the head and neck, presents a confusing problem for the clinician due to its unusual behavior. The individual cells have a bland microscopic appearance, and there is a predilection for neural invasion. Four cases of MAC are reported. All four cases demonstrate the difficulty with pathologic diagnosis. Follow-up of as long as 33 years begins to delineate the protracted nature of MAC. In addition, this paper includes the first report of a case of lymph node metastasis. Although resection may result in a significant defect, negative margins may not be achieved. Despite this, the defect can heal, as demonstrated by the cases described. In addition, MAC may recur many years later, irrespective of the status of the margins at the time of surgery. Given these unusual characteristics and the slowly progressive nature of MAC, strong consideration must be given to less radical surgical procedures, with close follow-up for grossly recurrent disease.

Irradiated soft tissue and its management.

The healing of a surgical wound is significantly affected by radiation. Radiation can affect all cells within its treatment field, thus making irradiated tissue more susceptible to trauma, infection, and irritation. In the irradiated patient, careful preoperative planning and a preventive approach to optimize conditions for wound healing are crucial to minimizing complications. This article describes the principles and management of common complications seen from irradiated soft-tissue wounds of the head and neck.

Growth factors in wound healing.

Growth factors are signal proteins that regulate the cellular processes in wound healing. By manipulating the actions of growth factors, it may be possible to accelerate or modify wound healing. Currently, intense research is being conducted throughout the world to investigate this possibility. In otolaryngology, the impact of improved wound healing could be tremendous. This article discusses the involvement of growth factors in soft-tissue healing that is relevant to otolaryngology.

Effects of nutrition on wound healing.

Optimal wound healing and its close relationship to a patient's positive nutritional balance is well known. For years, physicians have attempted to improve the metabolic status of patients after surgery or trauma. Currently, major emphasis is placed on perioperative nutritional status and its effect on postoperative wound healing. The intricacies of metabolism and healing are areas of current active research, in an effort to advance the quality of patient care. For the head and neck surgeon, wound healing is of paramount concern in areas of tumor extirpation, head and neck reconstruction, and maximization of postoperative functional recovery. To better explain why adequate nutrition is important in postoperative wound healing, we will provide a brief synopsis of nutrition and its relationship to wound healing.

Growth factors and wound healing in otolaryngology.

An immense amount of knowledge has been gained over the last decade in the realm of polypeptide growth factors. Only recently has this new information made an impact in otolaryngology. This article is a brief overview of peptide growth factors in relation to wound healing and otolaryngology.

The wound healing response to grafted tissues.

When a tissue graft is introduced into a healing wound, the inflammatory and proliferative stages of wound healing are significantly prolonged. This sustained stimulation at the surrounding graft site can develop into chronic inflammation, leading to fibrosis and connective tissue build-up around the graft. Persistence in chronic inflammation surrounding a tissue graft can lead to graft destruction or rejection. Thus, a basic understanding of soft-tissue wound healing in response to grafted tissue is important to optimize the long-term functional results of tissue grafts.