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Biomedical subjects

W H Eaglstein

Publications and source records attributed to W H Eaglstein.

At least 19 recordsLinked to original sources

Collagenase in wound healing: effect of wound age and type.

Collagenase is believed to be important for cell migration and collagen remodeling during tissue repair and regeneration. We have investigated collagenase concentrations in different types of surgically inflicted wounds in pigs. Collagenase was extracted from tissue homogenates of wounds by heating to 60 degrees C for 6 min in 0.1 M CaCl2. The molecular weight of latent collagenase was about 52 kDa. Activated collagenase produced the characteristic 3/4 fragment of collagen. Collagenase was assayed by the use of radiolabeled telopeptide-free collagen. To detect maximal collagenase activity, extracts were reduced and alkylated to destroy inhibitors, then activated with aminophenylmercuric acetate. Sutured incisions showed peak collagenase content on postoperative day 1 and thereafter steadily declining concentrations. Granulation tissue from non-sutured large defect full-thickness wounds showed high collagenase content on postoperative day 5 and then a sharp decline to day 7 followed by a slowly declining curve to postoperative day 21. Partial-thickness wounds exhibited a different time course, with collagenase increasing to peak concentrations on postoperative days 3-5; however, a large proportion of the detected collagenase was due to the adherent scab. By day 7 collagenase concentrations approached the low concentrations of normal skin when epithelialization was complete and the scab rejected. In general, collagenase shows an early maximum and then declines with postoperative time, with the sharpest decline occurring when epithelialization is complete.

Aging

Topical use of human recombinant epidermal growth factor (h-EGF) in venous ulcers.

A great deal of interest has been focused recently on the potential use of synthetic polypeptide growth factors to stimulate healing of chronic wounds. In this pilot double-blind randomized study conducted at a single center, we used human recombinant epidermal growth factor (h-EGF) to treat 44 patients with venous ulceration of the lower extremities. An aqueous solution (10 micrograms/mL) of h-EGF was applied topically to the ulcers twice a day until healing occurred or for a maximum of 10 weeks. Patients were evaluated weekly for measurements of ulcer size and for the formation of granulation tissue suitable for grafting. Nine patients were excluded from efficacy evaluation because of protocol violations. Therefore, 35 patients (17 h-EGF, 18 placebo) were evaluable for efficacy, and 44 patients (22 h-EGF, 22 placebo) were available for safety. The median baseline ulcer size for all patients was 18.5 cm2, and was not significantly different between h-EGF and placebo group (12.9 cm2 versus 19.2 cm2, respectively, P = .27). By study end, six (35%) of h-EGF treated patients and two (11%) in the placebo group had healed completely (P = .10). Another 6 patients (2 of 17 h-EGF, 4 of 18 placebo; P = .50) developed healthy granulation tissue that was suitable for grafting. The median ulcer size reduction was 7% for h-EGF versus 3% for placebo per week (P = .29), and 73% versus 33% at study end (P = .32). No untoward side effects were related to the application of h-EGF. We conclude that topical application of h-EGF, in the dose and manner used in this study, was safe but failed to significantly enhance re-epithelialization of venous ulcers. However, a greater reduction in ulcer size and a larger number of healed ulcers with the use of h-EGF are encouraging results.

Administration, Topical

Pericapillary fibrin cuffs in venous ulceration. Persistence with treatment and during ulcer healing.

A recent hypothesis suggests that venous hypertension leads to ulceration through the formation of pericapillary fibrin cuffs, which are presumed to impede the exchange of oxygen and other nutrients. In this report, we evaluated by direct immunofluorescence the presence of pericapillary fibrin at the edge of venous ulcers during the course of treatment with elastic compression. In an initial group of 23 patients studied at baseline, pericapillary fibrin cuffs were detected in 20 (91%) of 22 patients. The intensity of fibrin staining, rated blindly on a scale of 0 to 3, could not be correlated with several baseline parameters, including the clinical presence and extent of lipodermatosclerosis, ulcer size, venous recovery time, and transcutaneous oxygen measurements (TcPO2) taken next to the ulcer. Eleven of this initial group of 23 patients were randomly selected to receive elastic compression treatment, and were evaluated for the persistence of pericapillary fibrin at 60 and 120 days. Although a reduction (mean +/- SD = 50.2% +/- 25.7) in ulcer size occurred in 10 of the 11 patients, pericapillary fibrin was still present at the ulcer edge and with undiminished intensity. We conclude that pericapillary fibrin cuffs in venous ulcers persist with compression treatment and in spite of healing, and are unlikely to be directly related to the development of ulceration.

Adult

Stanozolol in treatment of leg ulcers due to cryofibrinogenaemia.

Five consecutive patients with cryofibrinogenaemia in association with painful leg ulcers and intravascular dermal thrombi were treated with stanozolol, an androgenic steroid with fibrinolytic properties. In all patients treatment was followed by rapid and striking pain relief and healing of the ulcers. Cryofibrinogenaemia was not detected on subsequent laboratory evaluation, and dermal intravascular thrombi had resolved on repeat histological examination.

Adult

The effect of electrical stimulation on the number of mast cells in healing wounds.

Many cutaneous disorders are associated with activation or increased numbers of mast cells. Electrical stimulation has been shown to be effective in treating many of these disorders. This study is designed to examine the effect of electrical stimulation on mast cells in acute wounds. Four pathogen-free pigs received 20 wounds, each of which was subjected to biopsy at various times after wounding. Half of the wounds were treated with electrical stimulation and the other half were treated with a sham electrode. The biopsy specimens were fixed in Carnoy's medium and stained with alcian blue and Nuclear Fast Red. Mast cells from both sets of wounds were counted and analyzed. Highly significant reductions in the number of mast cells were seen with electrical stimulation on days 1 and 2 compared with nonstimulated control wounds. Electron microscopy was performed to compare the stimulated and control mast cells for characteristic features in morphology, location, and evidence of degranulation. Electrical stimulation did not appear to induce degranulation. The ability of electrical stimulation to decrease the number of mast cells may be related to a reduction of either proliferation or migration of these cells and may prove to be a valuable therapeutic technique.

Animals

Human wound fluid from acute wounds stimulates fibroblast and endothelial cell growth.

One proposed mechanism for the beneficial effect of occlusive dressings on healing is the maintenance of contact between the wound bed and accumulated wound fluid, which is thought to contain growth stimulatory substances. We have examined the effect of human wound fluid on the in vitro growth of human dermal fibroblasts and umbilical vein endothelial cells. Acute wound fluid was collected from six patients undergoing split-thickness skin grafting. The acute wound fluid was sterilely collected daily from underneath a vapor-permeable membrane applied to the donor site and changed every 24 hours for 3 days postoperatively. After seeding in optimal growth media (control) on day 0, cultures of human dermal fibroblasts and umbilical vein endothelial cells were supplemented with or without acute wound fluid on the next day (day 1) and on day 3. As determined by cell counts, 2% acute wound fluid stimulated the growth of human dermal fibroblasts (p less than 0.05) and umbilical vein endothelial cells (p less than 0.01) when these cells were cultured in 2% fetal bovine serum and endothelial growth medium, respectively. Wound fluid from postoperative days 1 or 3 caused the same level of stimulation. The addition of an anti-platelet-derived growth factor antibody to wound fluid resulted in a 45% mean reduction in its stimulatory effect on fibroblast growth (p less than 0.02), suggesting that platelet-derived growth factor contributes to the observed effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Count

Recruitment of mononuclear cells into wounded skin: mechanism and modulation.

In conclusion, we have shown that the development of specialized endothelium that supports lymphocyte and monocyte adherence may be a common biologic event associated with tissue injury or disease processes in the skin. We have shown that the adherence process is potentially regulated by cytokines that are secreted by infiltrating mononuclear cells. Studies are now in progress to identify the putative endothelial ligands, their interactions with the receptors and the factors that lead to the expression of the adhesion molecules.

Animals

Wound healing. The effects of topical antimicrobial agents.

The effect of four commonly used topical antimicrobial agents on the rate of reepithelialization of clean wounds was evaluated in white domestic pigs. Neosporin Ointment was found to significantly increase the rate of reepithelialization by 25%, while Furacin significantly retarded the healing rate by 24%. Pharmadine, a preparation containing povidone-iodine, did not affect the rate of healing. Both Silvadene and its vehicle significantly increased the rate of reepithelialization by 28% and 21%, respectively. The effects of these agents cannot be explained on the basis of their antimicrobial activity.

Animals

Ultraviolet radiation-induced inflammation and leukocytes.

To evaluate the role of leukocytes in inflammation induced by ultraviolet radiation, the response of guinea pigs make leukopenic with cyclophosphamide was compared with the response of nonleukopenic animals. The response of leukopenic animals to UVB (295 nm) was significantly altered. Leukopenic animals and saline-treated (i.e., nonleukopenic) animals responded similarly to (1) UVC (250 nm), (2) UVA (340 nm) given after 8-methoxypsoralen pretreatment (PUVA), (3) intradermal histamine and (4) a topically applied prostaglandin analogue. These results suggest that leukocytes are important in UVB-induced inflammation but not in the inflammation induced by UVC or PUVA.

Animals

New methods for assessing epidermal wound healing: the effects of triamcinolone acetonide and polyethelene film occlusion.

Epidermal healing of superficial, excised wounds in domestic white pigs was evaluated visually and histologically after separation of the epidermis and dermis. The visual determination of epidermal healing correlated well with the histologic studies of surface re-epithelialization. Wounds healed 40% faster when occluded with polyethelene film. Topical triamcinolone acetonide treatment delayed healing (62% slower than control).

Animals

Systemic antibiotic therapy of secondary infected dermatitis.

Systemic cloxacillin therapy of secondarily infected dermatitis cloxacillin therapy become apparent produces a significant increase in healing when compared to a placebo. The effects of systemic after five days of treatment. A single pretreatment culture was not helpful in directing therapy.

Adolescent

Human essential fatty acid deficiency: treatment by topical application of linoleic acid.

An essential fatty acid (EFA) deficiency developed in a 19-year-old man who was being maintained on a long-term regimen of fat-free, intravenous hyperalimentation fluids. The EFA deficiency was reversed after 21 days by daily, topical application of linoleic acid to the patient's skin. The ratio of eicosatrienoic acid (20:3, n-9) to eicosatetraenoic acid (20:4, n-6) decreased to normal levels in the skin and serum with clinical improvement of the EFA deficiency syndrome. The cutaneous manifestations (scalp dermatitis, alopecia, and depigmentation of hair) were reversed with continued, topical application of safflower oil, which contains 60% to 70% linoleic acid.

Administration, Topical

Ultraviolet light and tar in the Goeckerman treatment of psoriasis.

In an attempt to evaluate and improve the Goeckerman treatment of psoriasis, combinations of tar and ultraviolet (UV) light were studied. The effects of UV irradiation alone, of curde coal tar (CCT) ointment alone, and of UV irradiation with 1% CCT ointment and with 6% CCT ointment on psoriatic lesions were compared. The combinations of 1% CCT ointment with UV irradiation and of 6% CCT ointment with UV irradiation were found to be equally effective. The combination of UV irradiation with ointment had little effect on psoriatic lesions. In most cases, the combination of 1% CCT ointment and UV irradiation was superior to high-concentration (6%) tar ointment without UV irradiation. This study suggests that UV light is an important component of the Goeckerman treatment ant that tar and UV irradiation are superior to tar alone.

Adolescent