Adam B. Weinfeld

Increased free fat-graft survival with the long-term, local delivery of insulin, insulin-like growth factor-I, and basic fibroblast growth factor by PLGA/PEG microspheres.

&NA; The present investigation evaluates the effects of longterm, local delivery of insulin, insulin‐like growth factor‐1 (IGF‐1), and basic fibroblast growth factor (bFGF) on fatgraft survival using a poly (lactic‐co‐glycolic‐acid)‐polyethylene glycol (PLGA/PEG) microsphere delivery system. Twelve‐micrometer PLGA/PEG microspheres incorporated separately with insulin, IGF‐1, and bFGF were manufactured using a double‐emulsion solvent‐extraction technique. Inguinal fat from Sprague Dawley rats was harvested, diced, washed, and mixed with (1) insulin microspheres, (2) insulin‐like growth factor‐1 microspheres, (3) basic fibroblast growth factor microspheres, (4) a combination of the insulin and IGF‐1 microspheres, and (5) a combination of insulin, IGF‐1, and bFGF microspheres. The treated fat grafts were implanted autologously into subdermal pockets in six animals for each group. Animals receiving untreated fat grafts and fat grafts treated with blank microspheres constituted two external control groups (six animals per external control group). At 12 weeks, all fat‐graft groups were compared on the basis of weight maintenance and a histomorphometric analysis of adipocyte area percentage, indices of volume retention and cell composition, respectively. Weight maintenance was defined as the final graft weight as a percent of the implanted graft weight. All growth factor treatments significantly increased fat‐graft weight maintenance objectively, and volume maintenance grossly, in comparison with the untreated and blank microsphere‐treated controls. Treatment with insulin and IGF‐1, alone or in combination, was found to increase the adipocyte area percentage in comparison with fat grafts treated with bFGF alone or in combination with other growth factors. In conclusion, the findings of this study indicate that long‐term, local delivery of growth factors with PLGA/PEG microspheres has the potential to increase fat‐graft survival rates. Further, the type of growth factor delivered may influence the cellular/stromal composition of the grafted tissue. (Plast. Reconstr. Surg. 105: 1712, 2000.)

De novo adipose tissue generation through long-term, local delivery of insulin and insulin-like growth factor-1 by PLGA/PEG microspheres in an in vivo rat model: A novel concept and capability

&NA; This study was undertaken to characterize the duration of long‐term growth factor delivery by poly(lactic‐co‐glycolicacid)‐polyethylene glycol (PLGA/PEG) microspheres and to evaluate the potential of long‐term delivery of insulin and insulin‐like growth factor‐1 (IGF‐1) for the de novo generation of adipose tissue in vivo. PLGA/PEG microspheres containing insulin and IGF‐1, separately, were produced by a double‐emulsion solvent‐extraction technique. In the first phase of the experiment, the in vitro release kinetics of the microspheres were evaluated for the optical density and polyacrylamide gel electrophoresis of solutions incubated with insulin‐containing microspheres for four different periods of time (n = 1). The finding of increased concentrations of soluble insulin with increased incubation time confirmed continual protein release. In the second stage of the experiment, 16 rats were divided equally into four study groups (insulin, IGF‐1, insulin + IGF‐1, and blank microspheres) (n = 4). Insulin and IGF‐1 containing microspheres were administered directly to the deep muscular fascia of the rat abdominal wall to evaluate the potential for de novo adipose tissue generation via adipogenic differentiation from native nonadipocyte cell pools in vivo. Animals treated with blank microspheres served as an external control group. At the 4‐week harvest period, multiple ectopic islands of adipose tissue were observed on the abdominal wall of the animals treated with insulin, IGF‐1, and insulin + IGF‐1 microspheres. Such islands were not seen in the blank micro sphere group. Hematoxylin and eosin‐stained sections of the growth factor groups demonstrated mature adipocytes interspersed with fibrous tissue superficial to the abdominal wall musculature and continuous with the fascia. Oil‐Red‐O stained sections demonstrated that these cells contained lipid. Computer‐aided image analysis of histologic sections confirmed that there were statistically significant increases in the amount of “ectopic” adipose neotissue developed on the abdominal wall of animals treated with growth factor microspheres. In conclusion, this study confirms the long‐term release of proteins from PLGA/PEG microspheres up to 4 weeks and demonstrates the potential of long‐term local insulin and IGF‐1 to induce adipogenic differentiation to mature lipid‐containing adipocytes from nonadipocyte cell pools in vivo at 4 weeks. (Plast. Reconstr. Surg. 105: 1721, 2000.)

Clinical and scientific considerations in leech therapy for the management of acute venous congestion: An updated review

Any surgical intervention that involves the manipulation of veins, large or small, carries the risk of acute venous congestion. Venous congestion is the product of an imbalance between arterial inflow and venous outflow, and results in the stasis of blood in the tissues that are normally drained by the affected veins. The resultant lack of tissue perfusion causes hypoxia, acidosis, and arterial thrombi formation, which can potentially progress to tissue necrosis and wet gangrene. In the past several decades, the use of leeches (Hirudo medicinalis) has been rediscovered as an effective method of relieving acute venous congestion. This updated review of leech therapy focuses on the use of medicinal leeches in a variety of clinical conditions characterized by acute venous congestion, and points out the experimental use of leeches in other pathological entities. A discussion of the recent scientific findings that explain the possible mechanisms of action of leech therapy is also provided.

Circumferential negative-pressure dressing (VAC) to bolster skin grafts in the reconstruction of the penile shaft and scrotum.

This paper presents 4 consecutive cases using negative-pressure dressings (VAC) to bolster skin grafts in male genital reconstruction. In this series reconstruction followed 1 case of tumor ablation and 3 cases of debridement of abscesses or Fornier’s gangrene. The VAC was applied circumferentially to the penis to secure skin grafts either directly to the penile shaft or to facilitate skin grafting to the scrotum. Graft areas ranged from 75 to 250 cm. All cases resulted in successful genital wound coverage; minor complications are described. Three practical points are brought forth. First, the VAC facilitates skin grafting to the complex contour of male genitalia. Second, the VAC can be applied circumferentially to the penis without the need for perfusion monitoring or fears of avascular necrosis. Third, with the use of the VAC, bolster use can likely be discontinued as early as 72 hours with good graft adherence and survival.

Augmentation of adipofascial flaps using the long-term local delivery of insulin and insulin-like growth factor-1.

The adipofascial flaps currently described in the literature frequently lack the volume requirements for reconstructive goals. In this study, the authors examined the use of long-term local delivery of insulin and insulin-like growth factor-1 (IGF-1) using polylactic-coglycolic acid/polyethylene glycol (PLGA/PEG) microspheres to augment inguinal adipofascial flaps based on the inferior epigastric vessels in the rat. Two flap models, the island flap and the limited dissection flap, were used to demonstrate simultaneous treatment and pretreatment modalities, respectively. Experimental groups received 12.5 mg of insulin microspheres (carrying 1 IU of insulin) plus 12.5 mg of IGF-1 microspheres (carrying 2.5 &mgr;g of IGF-1). A group undergoing the operation only (no treatment with microspheres) and a group treated with blank microspheres (no growth factor) served as external controls for the surgical procedure and the drug delivery device, respectively. In all groups (n = 5 animals in each), the contralateral flap served as an internal control. Upon harvest on postoperative day 28, the insulin and IGF-1–treated flaps in both models weighed statistically more than the internal control flaps and the two external control flaps. Likewise, on gross inspection, the adipogenic growth factor–treated flaps had greater volumes than the internal control flap groups and both of the external control flap groups (operation only and blank microspheres). Other intergroup comparisons suggested the absence of a systemic insulin and IGF-1 effect on adiposity. A histomorphometric analysis suggested (1) that insulin and IGF-1 treatment does not alter flap cell composition and (2) that flap augmentation is secondary to the stimulation of cell proliferation and adipocytic differentiation rather than the hypertrophy of mature adipocytes. Further evidence in favor of cell proliferation and differentiation was the discovery of nonanatomic, ectopic fat islands on the pedicle sheath of the treated flaps and the lack of variation in cell size distribution among groups. The authors concluded that the long-term local delivery of insulin and IGF-1 with PLGA/PEG microspheres is an effective method of adipofascial flap augmentation; this method increases the number of mature adipocytes rather than increasing the size of preexisting cells. (Plast. Reconstr. Surg. 106: 373, 2000.)

The comprehensive management of chemosis following cosmetic lower blepharoplasty

Background: Chemosis can cause persistent discomfort and aggravation in the postoperative period following surgery of the eyelids. This article focuses on chemosis associated with cosmetic lower blepharoplasty. The cause is multifactorial and includes exposure, periorbital edema, and postoperative lymphatic dysfunction. Methods: A chart review of 312 primary bilateral lower transcutaneous blepharoplasties was performed. Data were collected to identify the incidence of chemosis, define associated etiologic factors, develop a chemosis classification system, and outline a successful treatment algorithm. Results: The incidence of chemosis was 11.5 percent in this population of lower lid blepharoplasty patients. Chemosis presented intraoperatively or up to 1 week postoperatively. The median duration was 4 weeks, with a range from 1 to 12 weeks. Associated etiologic factors included conjunctival exposure, periorbital and facial edema, and lymphatic dysfunction. The four general patterns of presentation were classified as type 1, acute mild chemosis with complete lid closure; type 2, acute severe chemosis that prohibits complete lid closure (chemosis-induced lagophthalmos); type 3, subchronic chemosis that persists longer than 3 weeks; and type 4, chemosis associated with lower lid malposition. Successful treatment existed along a continuum from liberal lubrication to ophthalmic steroid preparations and ocular decongestants to eye-patching to minor surgical procedures such as drainage conjunctivotomy and temporary tarsorrhaphy. In all cases, chemosis ultimately resolved. Conclusions: Chemosis is a common complication of lower blepharoplasty. Pharmacologic, mechanical, and surgical therapies may be used alone or in combination for the successful management of chemosis. Prevention by minimization of triggering factors intraoperatively and immediately postoperatively is important.

Topographic mapping of the superior transverse scapular ligament: a cadaver study to facilitate suprascapular nerve decompression.

&NA; Division of the superior transverse scapular ligament for decompression of suprascapular nerve entrapment can be curative. However, the superior transverse scapular ligament can be difficult to locate, and large incisions are often required. This study was designed to determine the topographic coordinates of the superior transverse scapular ligament to permit reproducible surgical localization and reduce incision size. In 20 cadavers, the superior transverse scapular ligament was identified through a superior approach. Measurements were obtained from the superior transverse scapular ligament to external landmarks. The superior transverse scapular ligament was located 1.3 ± 0.3 cm (± SD) posterior to the posterior border of the clavicle and 2.9 ± 0.8 cm from the acromioclavicular joint in a two‐dimensional surface plane. The depth of the superior transverse scapular ligament from the skin surface was 3.9 ± 0.7 cm. An incision (mean length, 6.3 ± 0.7 cm) derived from a novel system of planning marks facilitated access to the superior transverse scapular ligament. The authors conclude that the superior transverse scapular ligament can be located consistently through an incision located on the superior aspect of the shoulder on the basis of palpable topographic landmarks. The superior approach permits small incision size and the maintenance of local muscle anatomic integrity.

Purse-String Nipple Areolar Reconstruction

We present a surgical technique of nipple areolar reconstruction that uses a purse-string to increase areolar projection while reducing loss of nipple projection. A permanent purse-string is used around a modified CV flap to advance tissue centrally to the base of the nipple reconstruction. Two opposing hemiareolar island flaps are advanced toward the base of the nipple to add tissue volume. The resulting circumareolar full thickness skin is closed using a permanent purse-string suture. Synching the purse-string suture produces an effect similar to that of a periareolar mastopexy and enhances areolar projection. Eighty-two patients underwent 108 nipple areola reconstructions. Ninety-six percent of the patients achieved good results without any flap loss or suture infections. Revision surgery was necessary in 4 patients for minor problems including asymmetry or loss of projection. The purse-string nipple areolar reconstruction method described results in a high rate of maintenance of projection and patient satisfaction.

1998 ARRS President's Award. The potential of in vivo vascular tissue engineering for the treatment of vascular thrombosis: a preliminary report. American Roentgen Ray Society.

OBJECTIVE Current gene therapy and tissue engineering protocols suffer from a number of inherent limitations. In this study, we examine the feasibility of a new approach for the treatment of vascular thrombosis: in vivo tissue engineering. MATERIALS AND METHODS Rabbit femoral veins were transfected in situ with either a previously characterized adenoviral-construct-expressing tissue plasminogen activator or a viral (adenoviral-construct-expressing beta-galactosidase) or nonviral (buffer) control and used as cross sections (n = 3). Treated veins were then harvested and grafted into the ipsilateral common femoral artery as an interposition vein graft. A potent stimulus for thrombus formation was then introduced into the recipient artery downstream of the graft. Six days later, the rabbits were sacrificed, and the grafts and downstream arteries were harvested. Vessel segments were then examined for thrombus according to defined anatomic zones. Transfection efficiency and presence of smooth muscle cells in the vein graft were also evaluated. RESULTS The engineered vein graft showed a significant reduction in thrombus formation within both the graft and the downstream artery relative to nonviral (buffer) and viral (adenoviral-Rous sarcoma virus beta-galactosidase [Adv/RSV-betagal]) controls. Underlying endothelial cell transfection efficiency of 90% was observed in viral controls (Adv/RSV-betagal). A 2.4-fold increase in smooth muscle alpha-actin positive cells in the engineered vein graft was seen compared with nonviral (phosphate-buffered saline) controls. A 10-fold increase in smooth muscle alpha-actin-positive cells in the engineered vein graft relative to viral (Adv/RSV-betagal) controls was also observed. CONCLUSION In vivo tissue engineering is a new paradigm in molecular medicine that is a viable alternative to conventional gene therapy and tissue engineering for the treatment of vascular thrombosis.

Neural anatomy of the radial forearm flap.

&NA; Typically the lateral antebrachial cutaneous nerve alone is used to innervate the radial forearm free flap when a sensate flap is required. The authors desired, by means of fresh cadaveric microdissections and by means of local anesthetic injections in living subjects, to map the sensory nerve territories of this flap. Eight radial forearm flaps were elevated and the medial antebrachial cutaneous nerve (MABC), lateral antebrachial cutaneous nerve (LABC), and superficial radial sensory nerve (SRSN) were dissected with the aid of an operating microscope (2.5‐10×) and traced to their dermal insertions. In the injection study, the MABC, LABC, and SRSN in eight forearms of 4 subjects were blocked sequentially with 2% lidocaine injections. The resulting sensory deficit from each injection was mapped on the skin and superimposed on the marked radial forearm flap territory. Distribution of the three dissected nerve regions and the sensory deficit after injection were determined by digital images and computer analysis. During flap dissections, mean nerve distributions of total flap area were as follows: LABC, 61.8% (range, 48.3‐71.6%); MABC, 33.8% (range, 30.5‐38.9%); and SRSN, 34.6% (range, 26.8‐44.1%). After nerve block the mapped sensory areas were as follows: LABC, 62.3% (range, 44.5‐88.5%); MABC, 19.6% (range, 8.0‐35.8%); and SRSN, 19.5% (range, 9.9‐26.3%). At least 40% of the total flap area was not innervated by the LABC as identified both by nerve dissection and sensory local anesthetic blockade. By including the LABC, MABC, and SRSN in the radial forearm flap, both the theoretical and the clinically determined useful sensory innervation of the radial forearm flap potentially would be increased. Boutros S. Yuksel E, Weinfeld AB, Alford EL, Netscher DT. Neural anatomy of the radial forearm flap. Ann Plast Surg 2000;44:375‐380