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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
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

The effect of topical nitroglycerin on transcutaneous oxygen.

The use of topical nitroglycerin has been reported to aid the healing of chronic skin ulcers. In this study, the effect of 2% nitroglycerin ointment on transcutaneous oxygen pressure (TcPO2) was investigated in skin adjacent to the area of ointment application. Topical nitroglycerin caused a two-fivefold decrease in TcPO2 in skin next to or up to 9 cm away from the site of application of the ointment.

Administration, Topical↗
PubMed1991

Heterogeneity in oxygen diffusion around venous ulcers.

The pathogenesis of venous ulceration is thought to involve the formation of fibrin cuffs around dermal capillaries. Consistent with a barrier effect of fibrin, it has been shown that the dermal diffusion of oxygen, as measured by transcutaneous oxygen pressure (TcPO2), is decreased in limbs affected by venous ulcer. However, it is unknown whether oxygen diffusion around the perimeter of venous ulcers is uniformly affected. In this study, we investigated TcPO2 values at four different quadrants around the ulcers of 14 patients, the contralateral leg of five patients with unilateral ulcers, and the leg of six normal individuals. These values were also compared to TcPO2 measurements at the chest. Our results indicate that, whereas TcPO2 values in limbs affected by venous ulcers are much lower than normal, there is a great deal of variability in oxygen diffusion around individual ulcers. These findings may represent a heterogeneity in the disease process affecting the leg.

Adult↗
PubMed1991

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↗
PubMed1991

Faster healing and less pain in skin biopsy sites treated with an occlusive dressing.

We prospectively studied 174 patients on whom 226 unsutured parallel incisional (shave) and 3-mm punch skin biopsies were performed. Two wound-care programs, occlusive dressing therapy and conventional therapy, were compared. The biopsy sites were evaluated after 1 or 2 weeks for healing, pain, and infection. We found that healing was unrelated to the indication for biopsy or the patients' age, gender, or race. Occlusive dressing therapy-treated shave biopsy sites were 3.83 times more likely to be healed than those treated with conventional therapy. Regardless of the treatment method, a facial shave biopsy site was 3.6 times more likely to be healed than a biopsy site in other locations. No punch biopsy site had healed after 1 week. At 2 weeks, only 7% and 36% of conventional therapy- and occlusive dressing therapy-treated punch biopsy sites, respectively, had healed. Pain at the biopsy site was six times more common in both shave and punch biopsy sites treated with conventional therapy. The absence of pain with occlusive dressing therapy was significant for both types of biopsy. One punch biopsy site treated with conventional therapy became infected, and one treated with occlusive dressing therapy was suspected of being infected. Forty patients, who had biopsy sites treated with both therapies, preferred occlusive dressing therapy over conventional therapy by a ratio of 3:1 because of ease of wound care and lack of pain. We conclude that occlusive dressing therapy may be the wound management of choice for shave biopsy sites. Since punch biopsy sites do not heal readily, it may be more appropriate to suture them, at least until therapies are developed that more effectively speed their healing.

Adult↗
PubMed1990

Occlusive dressings. Does dressing type influence the growth of common bacterial pathogens?

We studied the effect of different occlusive dressings and of air exposure on the growth of four pathogenic bacteria in wounds. Partial-thickness wounds on domestic pigs were inoculated with Staphylococcus aureus, Clostridium perfringens, Bacteroides fragilis, or Pseudomonas aeruginosa. Each wound was covered with three dressings (DuoDERM, Opsite, or Vigilon), or left exposed to air. Groups of wounds were sampled at 24, 48, and 72 hours. Staphylococcus aureus reached high levels beneath all of the dressings and in the air-exposed wounds. The numbers of C perfringens and B fragilis were greatly reduced in the air-exposed wounds and slightly reduced in the Opsite-covered wounds. The numbers of P aeruginosa were greatest in the Opsite- and Vigilon-covered wounds. The results indicate that occlusive dressings are not indicated in wounds that clinically appear to be grossly contaminated or that may contain anaerobic organisms.

Animals↗
PubMed1990

Second-degree burn healing: the effect of occlusive dressings and a cream.

Because occlusive dressings and some creams have been found to speed epithelialization of blade-induced wounds, we studied the effect of two occlusive dressings and a polyglycerylmethacrylate cream containing low concentration of fibronectin on epithelialization in second-degree burn wounds. Cylindrical brass rods were heated in a boiling water bath, removed, wiped dry, and placed (6 sec) on the skin of domestic pigs. The burned epidermis was removed and each burn wound was assigned to one of the following treatment groups: (1) air-exposed, (2) DuoDERM (hydrocolloid dressing; Squibb Co., New Jersey), (3) Opsite (polyurethane dressing; Smith & Nephew, New Jersey), or (4) experimental cream. Several burn wounds were excised from each treatment group on Days 6 to 14 after wounding. The excised burn wounds were incubated in 0.5 M NaBr for 24 hr which allowed separation of the epidermis from the dermis. The epidermis was examined macroscopically for defects in the area of the burn. Specimens were considered healed when a defect was not present. Neither of the occlusive dressings changed the rate of epithelialization as compared to air exposure. Wounds which were treated with the experimental cream epithelialized faster than the air-exposed wounds (P less than 0.025).

Administration, Topical↗
PubMed1990

Recruitment of mononuclear cells by endothelial cell binding into wounded skin is a selective, time-dependent process with defined molecular interactions.

Wound healing involves a complex series of interactions between cells in the dermis and epidermis, and important relationships exist between keratinocytes and resident dermal cells. Monocytes and lymphocytes secrete cytokines that are capable of stimulating dermal repair and influencing keratinocyte and fibroblast migration and proliferation, although the mechanism by which mononuclear cells are recruited into the wound is unknown. We have tested the hypothesis that in wounded skin specialized endothelial cells are induced to mediate peripheral blood mononuclear cell (PBMC) emigration from the vasculature into the dermis. For this purpose, partial-thickness wounds made with a keratome on the backs of domestic pigs were excised 0 to 9, 12, 15, and 21 d after wounding. The biopsies were then tested for the capacity to adhere selectively to PBMC. The results indicated that PBMC overlaid onto sections of wounds from day 4 to 15 adhered selectively to dermal endothelium, with two distinct peaks of adherence observed on day 7 and day 12. In contrast, PBMC did not adhere to the tissue sections when overlaid onto frozen sections of normal skin or 0-, 1-, 2-, 3-, and 21-d-old wounded skin. Additional studies on the binding properties of PBMC subsets revealed that monocytes adhered maximally at day 7, whereas T cells adhered optimally at day 12 post-wounding. Furthermore, the adhesion process was energy and magnesium dependent but not calcium dependent and involved surface protein and carbohydrate moieties on PBMC surface. Pre-treatment of PBMC with monoclonal antibodies against the LFA-1 adhesive receptors inhibited the binding by greater than 80%, suggesting that LFA-1 adhesive receptors play an important role in the binding process. These studies provide evidence that the recruitment of monocytes and lymphocytes into wounds is an active, dynamic, and regulated process mediated at least in part by specific adhesive interactions between mononuclear leukocytes and dermal endothelial cells.

Animals↗
PubMed1990

Protein C and protein S plasma levels in patients with lipodermatosclerosis and venous ulceration.

Lipodermatosclerosis of the lower extremity, with or without ulceration, is a common manifestation of severe venous disease and the result of sustained venous hypertension. The latter is generally a sequela of deep vein thrombosis. Factors that enhance clot formation or impair fibrinolysis contribute to the pathogenesis of venous disease. It is already established that faulty fibrinolysis may play a pathogenic role in patients with venous disease. We examined the possibility that patients with venous disease have abnormally low plasma levels of proteins C and S, two proteins whose deficiencies have been reported to cause an increased frequency of thromboembolic disease. Using immunologic and functional assays for plasma proteins C and S, we found that 4 (21%) of 19 patients with lipodermatosclerosis and leg ulcers had abnormally low levels of protein C or protein S. One of 7 patients with lipodermatosclerosis without ulceration had a profoundly depressed level of protein C and a history of cerebral stroke at a young age. Plasma levels of protein C were normal in five patients with arterial insufficiency severe enough to cause leg ulceration. We conclude that abnormally low plasma levels of proteins C and S may be found in patients with lipodermatosclerosis and venous ulceration. As with the abnormally low fibrinolytic activity in these patients, our findings indicate a possible propensity for increased thrombotic disease.

Adult↗