Search

Increased numbers of mast cells are affiliated with a broad spectrum of pathologic skin conditions, including ulcers, atopic dermatitis, neurofibromatosis, hemangiomas, keloids, and hypertrophic scars. It has been proposed that mast cells play a primary pathophysiologic role in these disorders and that their presence represents not merely a secondary event. While investigating their recent hypothesis that positively charged cross-linked diethylaminoethyl dextran (CLDD) beads potentiate cutaneous wound healing, the authors serendipitously observed increased numbers of mast cells in the deep dermis of wounds treated with CLDD beads. The authors propose that mast cells may play an important role in the modulation of healing seen with CLDD beads. Incisional wounds were studied in 30 Sprague-Dawley rats partitioned into two groups that were killed 7 or 14 days after wounding. The wounds were treated with positively, negatively, or neutrally charged CLDD beads. Physiologic saline served as a control. At the designated times after incisional wounding, biopsy specimens were tested for wound breaking strength or processed for histologic testing, fixed in 4% paraformaldehyde, and stained with Giemsa and Goldner-Masson trichrome. Mast cells were counted under light microscopy in a blinded fashion and were expressed as the number of cells per millimeter squared. Significant increases in the number of mast cells were observed in the deep dermis of incisional wounds after implantation with positively or negatively charged CLDD beads. In contrast, neutrally charged beads had no effect on mast cell numbers. At 7 days, the incisions treated with positively charged beads averaged 2.1 times more mast cells compared with those treated with physiologic saline or neutrally charged beads, whereas the incisions treated with negatively charged beads displayed 3.2 times more mast cells. By day 14, the incisions treated with positively charged beads averaged 2.5 times more mast cells than those wounds treated with saline or neutrally charged beads; the incisions treated with negatively charged CLDD beads had 3.4 times more mast cells. The 7-day tensiometric data indicated that wounds treated with negatively charged CLDD beads had increased breaking strength compared with wounds treated with neutrally charged beads or saline (1.8 and 1.7 times, respectively; p = 0.01 and p = 0.02). Wounds treated with positively charged beads also showed increased breaking strength compared with wounds treated with neutrally charged beads or saline (1.5 and 1.4 times greater); however, this did not reach statistical significance. There was no apparent difference in breaking strength when neutrally charged beads were compared with those treated with saline. At 14 days, there was no statistically significant difference in wound breaking strength between different treatments. These findings are clinically germane to the assessment of proposed therapeutic applications of CLDD beads for a variety of impaired wound-healing states. Furthermore, if increased mast cell populations are intimately linked to hypertrophic scar and keloid formation, the results of the authors' study suggest that CLDD bead therapy of cutaneous wounds may lead to pathologic wound healing in humans.

Bone regeneration promoted by acidic recombinant human fibroblast growth factor (rhFGF-1), rabbit demineralized bone matrix (rDBM), and a fibrin (f) delivery system was measured in critical-sized defects in rabbits' radii. A unilateral segmental defect 20 mm in length was prepared in radii of 48 skeletally mature New Zealand White rabbits divided equally between 4- and 8-week cohorts. The temporal cohorts were divided equally among four treatment groups: rDBM, rDBM/f, rDBM/rhFGF-1/f, and rhFGF-1/f. Data for the fifth group, untreated critical-sized defects, were exploited from previous published reports from this laboratory. In response to experimental treatments, radiomorphometric and histomorphometric methods were used to derive quantitative outcome data that were tested by analysis of variance and post hoc multiple comparison tests (significance p

Enhanced cutaneous wound healing by positively charged cross-linked diethylaminoethyl dextran beads (CLDD) was studied in a standardized incisional wound model in 20 adult and 20 geriatric Macaca mulatta (rhesus) partitioned equally over five time periods. Physiologic saline served as a control. Soft-tissue linear incisions were prepared between and 1 cm inferior to the scapulae. There were four incisions per rhesus; each incision was 1.5 cm long with 1 cm of undisturbed tissue between incisions, and both the experimental CLDD and physiologic saline treatments were administered to each rhesus. The incision treatments were either CLDD and soft-tissue closure with 4-0 BioSyn sutures or sterile physiologic saline and closure with 4-0 BioSyn sutures. The hypothesis was CLDD would enhance cutaneous wound repair. Verification of the hypothesis consisted of clinical examinations and histologic and tensiometric evaluations on biopsy specimens at 10 and 15 days, whereas 5-day and 2- and 4-month groups were assessed clinically and biopsy specimens were assessed histologically. The clinical course of healing for all groups was unremarkable. At 10 days, incisions in adult rhesus treated with CLDD had a 30-percent greater tensile strength compared with the physiologic saline-treated incisions (p = 0.01), whereas for geriatric rhesus, the CLDD treatment proved to be 15 percent greater in tensile strength compared with the physiologic saline cohort (p = 0.11). By day 15, incisions in adult rhesus were 26 percent stronger than the saline treatment group (p = 0.07), and the difference was 36 percent (p = 0.02) for the geriatric rhesus. From 5 through 15 days, histologic observations revealed a gradual decrease in quantity and integrity of CLDD, with no remnants of CLDD at either 2 or 4 months. Macrophages and multinucleated giant cells were localized in the dermis and were associated with the CLDD. These cells decreased commensurately with the decrease of CLDD beads. The data suggest that CLDD can enhance significantly the tensile properties of healing cutaneous wounds in both adult and geriatric rhesus. Moreover, if the wound healing is enhanced in geriatric patients, this finding may be clinically germane to conditions where wound healing is compromised, such as in diabetics and patients on steroids.

The effectiveness of prophylactic mastectomy in the prevention of breast tumors was studied in spontaneous breast-tumor-forming C3H mice. Prolactin levels were assayed to determine if this hormone was related to the incidence of mammary tumors. Two-hundred and fifty-six 1-month-old C3H mice were divided into four groups (control, 1; sham surgery, 2; mammectomy 50 percent, 3; and mammectomy 100 percent, 4). At the time of sacrifice (0 to 1 year postoperatively) estrus cycles were determined, ventral skin (breast) and ovaries were removed for histology, and serum was collected for prolactin assays. Prolactin levels 24 hours postoperatively were significantly elevated (p less than 0.01) in groups 2 to 4 when compared with group 1. Six months postoperatively, prolactin levels were significantly higher (p less than 0.05) in mice with tumors compared with those without tumors in groups 3 and 4. There were no differences in tumor incidence between the four groups. At 12 months postoperatively, no differences in prolactin levels were noted, but group 2 animals had the highest incidence of mammary tumors (89 percent; p less than 0.01) when compared to groups 3 and 4. Mammary tumor incidence was not decreased by 50 percent or 100 percent mammectomy in C3H mice. Prolactin levels rose in response to surgery and/or anesthesia and remained elevated only in tumor-bearing mice who underwent mammectomy, an occurrence similar to that reported in humans.

A subinfective dose of Staphylococcus aureus (6 X 10(6)) does not produce wound infection in the rat model. Reducing the dosage (concentration) of epinephrine results in decreased numbers of viable bacteria in tissue and a lower incidence of wound infection in this model.

The use of 1-mm ID by 1-cm-long expanded polytetrafluoroethylene microvascular grafts in various positions in two experimental animals did not compare favorably with the use of autogenous vein interposition grafts in controls. Light microscopy and scanning electron microscopy showed that early fibrin deposition at the anastomosis lines is followed by fully activated coagulation of the grafts. Use of antiplatelet and anticoagulant drugs, changes in techniques, and alterations in the graft material are possible future directions for improved patency with expanded polytetrafluoroethylene microvascular grafts.

In an attempt to find a vasoconstrictor with less detrimental local and systemic effects than epinephrine, the effects of phenylephrine, a pure alpha agonist, on tissue gas tension, bleeding, infection rates, and lidocaine absorption were studied. All concentrations of phenylephrine significantly reduced tissue PO2 within 10 minutes of injection, and reduction of PO2 was dose-dependent. Phenylephrine 1:10,000 produced significant bacterial growth when simultaneously injected with 6 X 10(6) Staphylococcus aureus. Bacterial growth was insignificant with 1:20,000 phenylephrine and absent with 1:40,000 phenylephrine. Blood loss from a standard wound was significantly reduced at all concentrations of phenylephrine. Lidocaine absorption was significantly reduced with 1:20,000 and 1:40,000 phenylephrine. In a rat model, 1:40,000 phenylephrine significantly reduced blood loss and lidocaine absorption, produced minimal reduction of tissue PO2, and did not enhance bacterial invasion.