Original articles: ease of wound closure as an endpoint of treatment efficacy.

New treatments for chronic wounds require carefully performed clinical trials with significant endpoints. Total wound closure is the only endpoint currently accepted by the Food and Drug Administration. This study describes a scale that measures ease of wound closure and applies it to a four-arm prospectively randomized, blinded pressure ulcer trial of recombinant human platelet-derived growth factor-BB. Following validation of interrater reliability, 83 evaluable subjects' photographs were given a weekly ease of closure score by four raters blinded to treatment. The change of ease of closure score was correlated with the change of wound area and volume. Each ease of closure score was given a procedural cost. Results showed ease of closure did not directly correlate with either wound area or volume, suggesting that it was measuring additional information. The mean change in ease of closure score was 6 for subjects treated with 100 microg recombinant human platelet-derived growth factor-BB daily; 5 for those treated with 300 microg growth factor daily or 100 microg recombinant human platelet-derived growth factor-BB bid; and 4 for those treated with placebo. The cost savings ranged from $7200 for the group receiving 100 microg recombinant human platelet-derived growth factor-BB daily to $6300 for the controls. Outcomes in all 4 groups were significantly improved from their starting evaluation (p < 0.001). Based on this study, ease of closure is a verifiable endpoint that can be related to cost efficiency and may be a measure of efficacy.

Benign symmetric lipomatosis (Madelung's disease).

Benign symmetric lipomatosis, also known as Madelung's disease, is a rare condition characterized by massive fatty deposits arranged symmetrically around the neck, shoulders, and arms. These patients might present for liposuction and body contouring. Although infrequently encountered in the average plastic surgeon's practice, this condition should be considered when evaluating candidates for these procedures. The deformity is associated with chronic alcohol use and also with malignant tumors of the upper airways. The deformity is prone to recurrence and its surgical treatment often results in less than optimal aesthetic outcomes. Despite this fact, surgical removal via either direct excision or suction-assisted lipectomy provides the only real hope of palliation. This report describes a patient with this deformity and a review of the literature.

Differential production of apoptosis-modulating proteins in patients with hypertrophic burn scar.

BACKGROUND: The biochemical and cellular pathways resulting in the production of proliferative scar in the thermally injured patient remain incompletely elucidated. A promising area of investigation is the phenomenon of programmed cell death and its modulation. The following study was designed to quantify differential levels of the bcl-2 protooncogene and the Fas cell surface receptor, two apoptosis-modulating proteins, in the peripheral blood mononuclear cell (PBMC) fractions of burn patients with hypertrophic scar versus those considered to have healed normally. The study also encompassed an immunohistochemical examination of fibroblasts in vitro, to identify differential levels of Fas, bcl-2, and interleukin converting enzyme (ICE). METHODS: PBMC fractions were isolated from two matched burn patient cohorts of 10 patients each, the experimental group carrying the clinical and histopathologic diagnosis of hypertrophic burn scar. The supernatant from each mitogenically stimulated specimen was halved and subjected to the Fas/APO-1 enzyme-linked immunosorbent assay (ELISA) and the bcl-2 ELISA. Results for each assay were compared between groups by unpaired t tests. Further biopsy specimens of isolated proliferative scar were used in vitro to analyze the role of these apoptosis-modulating proteins and ICE. This immunoperoxidase technique was analyzed qualitatively. RESULTS: The expression of the bcl-2 protein in the PBMC fractions of the burn patients with hypertrophic scar is significantly elevated in comparison to the control cohort (307.72 +/- 72.29 u/ml vs 31.55 +/- 6.73 u/ml; P = 0.0042). The quantitative levels of the Fas receptor did not differ significantly between the groups, respectively (0.3988 +/- 0.179 u/ml vs 0.2899 +/- 0.066 u/ml; P = 0.5787). Immunoperoxidase staining of proliferative scar fibroblasts and those from surrounding skin revealed relatively decreased levels of membrane-bound Fas and ICE. bcl-2 was not detectable in these specimens. CONCLUSIONS: Differential expression of the bcl-2 protooncogene and the Fas cell surface receptor in the PBMC fraction of patients with burn injuries may suggest a disequilibrium in a complex biochemical signaling mechanism mediating programmed cell death. The increased levels of bcl-2 could be responsible for delayed fibroblast apoptosis, resulting in the disruption of normal healing and subsequent hypertrophic scarring. This is confirmed by an in vitro examination of wound fibroblasts versus those from surrounding uninjured skin. This immunoperoxidase technique reveals a localized relative decrease in Fas and ICE, two apoptosis-inducing proteins, at the level of the fibroblast in the proliferative scar specimen.

Optimization of the MGH repair using an algorithm for tenorrhaphy evaluation.

Previous investigations have demonstrated the superior strength and toughness of the MGH four-strand tendon repair technique and shown that it neither weakens during maximum tendon softening nor interferes with healing in an in vivo rabbit model. In the current study, the biomechanical performance of the modified Becker (MGH) and the modified Kessler repairs were compared in situ using a dynamic human cadaveric model to evaluate strength, toughness, glide efficiency, and operator variability. Three different surgeons performed a total of 42 zone II flexor digitorum profundus repairs in 14 fresh human cadaver hands. The modified Becker (MGH) repairs were stronger (79 +/- 3 versus 64 +/- 4 N; p < 0.01) and tougher (0.092 +/- 0.002 versus 0.078 +/- 0.003 J; p < 0.01) than the Kessler repairs while allowing equally efficient glide (32 +/- 6 versus 33 +/- 4 percent; p > 0.9). Strength was operator-dependent only for the modified Kessler repair (p < 0.005). We then established the optimal configuration of the MGH tenorrhaphy (number of preloaded crosses on either side of the tendon transection) by examining gap resistance ex vivo. Fifty-one MGH flexor tendon repairs were performed on explanted fresh human cadaver tendons. The experimental groups were randomly assigned to receive 0, 1, 2, 3, or 4 crosses on each side of the tenorrhaphy. Strength and toughness to gap formation and to ultimate failure were assessed tensiometrically. The MGH two-cross configuration was most resistant to gap formation (peak load 39 +/- 3 N; p < 0.05), establishing this configuration as the optimal design of this four-strand crisscrossing repair technique. The augmented Becker (MGH) repair is significantly stronger and tougher than the modified Kessler repair and demonstrates no operator dependence. It is a superior technique for zone II tenorrhaphy in the human hand. An algorithm is presented as a systematic approach that includes the important elements necessary for the rigorous biomechanical evaluation of any tendon repair technique.

Debilitating silicone granuloma of the penis and scrotum.

The restoration and improvement of body contour have intrigued surgeons for over 100 years, generating much interest in the subcutaneous/intradermal injection of highly viscous fluids. The local complications of liquid silicone injection have been well documented over the past 30 years. Although Dow-Corning has not made medical-grade liquid silicone available for use in humans without an approved research application since 1966, practitioners, both licensed and unlicensed, have administered these injections worldwide for a variety of indications throughout the body. There is little or no information concerning the adulteration of these injectates. To date, there have been four case reports of penile injections--the indications being evenly split between the treatment of impotence/sexual inadequacy and augmentation. The most recent description was published in 1982. We present a case of debilitating silicone granuloma of the penis and scrotum secondary to large-volume injections into the corpora cavernosae and penile soft tissues administered in Belgium 14 years prior to presentation. The development of a silicone foreign body reaction, massive edema, and subsequent impotence lends itself to a clinical diagnosis and aggressive treatment with wide local excision and appropriate soft-tissue coverage. The metabolic fate of silicone in vivo remains inadequately characterized and a fertile area for research as new methods involving nuclear magnetic resonance spectroscopy have been devised to identify silicone and highly coordinated silicone complexes.

Infrainguinal revascularization for limb salvage in patients with end-stage renal disease.

We studied the efficacy of infrainguinal bypass for limb salvage in patients with end-stage renal disease. The patency of 42 femoropopliteal and femorodistal bypasses, performed for limb salvage in 37 patients with end-stage renal disease, was assessed with Doppler ultrasonography and dye tests. Patency rates and limb salvage were determined by life-table analysis. Average age was 45 years (range, 28 to 61 years); 23 of the 37 were men. Twenty-three patients had diabetes mellitus, and 16 were smokers. Bypass procedures were done in 32 instances while the patients were maintained with chronic hemodialysis and in five instances with peritoneal dialysis; in five instances the patients had had successful renal transplantation. Indications for revascularization included pain at rest, nonhealing ulcer, or distal gangrene. Femoropopliteal bypass was done in 32 limbs; 10 were more distal procedures. Reversed saphenous vein was the conduit in 30 cases; prosthetic material was used in the remainder. Autogenous material was used in all distal bypasses. Four patients required graft revision during the initial hospitalization, but none thereafter. Two patients died within the operative period, nine within 18 months of operation. Nine major operations were required. Three-month cumulative graft patency was achieved in 41 cases and corresponding limb salvage in 33 cases; 18-month patency was achieved in 34 cases and overall limb salvage in 33 cases. Success of limb salvage most closely correlated with preoperative ankle-brachial ratio and level of bypass required.