William H Eaglstein - Academia.edu (original) (raw)

Papers by William H Eaglstein

Archives of Dermatology, 2011

Archives of Dermatology, 1999

Background: Inherited epidermolysis bullosa (EB) is a mechanobullous disorder. The Dowling-Meara ... more Background: Inherited epidermolysis bullosa (EB) is a mechanobullous disorder. The Dowling-Meara variant, a subtype of EB, is characterized by widespread blister formation that may include the oral cavity and nails. Many patients with the Dowling-Meara phenotype are at increased risk of sepsis and death during infancy. The treatment of EB is generally supportive. The tissue-engineered skin used (Apligraf) is a bilayered human skin equivalent developed from foreskin. It is the only Food and Drug Administration-approved skin equivalent of its kind. It is approved for the treatment of venous ulcers of the lower extremities. It has also been used to treat acute wounds, such as graft donor sites and cancer excision sites.

Journal of Investigative Dermatology, 1999

Dermatologic Clinics, 2005

Cyanoacrylates (CAs), first produced in 1949 [1], are liquids that polymerize in the presence of ... more Cyanoacrylates (CAs), first produced in 1949 [1], are liquids that polymerize in the presence of moisture to form adhesives, glues, and films. The surgical use of these compounds was first proposed by Coover et al [2] in 1959. The short-chain cyanoacrylates (methyl, ethyl) [3,4] proved to be extremely toxic to tissue, however, preventing their widespread use as tissue glues. The short-chain CAs are used in nonmedical products, such as Krazy glue (Elmer's, Columbus, Ohio), and although they are not intended for medical use, dermatologists have been quoted in the popular press as recommending these glues for the treatment of fissures on fingers and toes [5]. Butyl cyanoacrylate (BCA), an intermediate-length CA, is not toxic when applied topically. Although it is not approved by the US Food and Drug Administration (FDA) for use in the United States, it has been used in Europe and Canada for middle ear procedures, to close cerebrospinal leaks, to repair incisions and lacerations, and to affix skin grafts [6-12]. Recently, a longer chain CA, octyl-2-cyanoacrylate (2-OCA), has been approved by the FDA and is now marketed (Dermabond topical skin adhesive) for closure of lacerations and incisions in place of sutures or staples. Even more recently, a 2-OCA formulated for greater flexibility, Liquid Bandage, has been approved for use in the over-the-counter market in the United States for the treatment of minor cuts and abrasions. This article discusses the use of CAs for their original cutaneous use as glues for the repair of lacerations and incisions and for their more recent use as films for use as dressings in the treatment of abrasions and wounds.

Journal of the American Academy of Dermatology, 2008

Background-Venous leg ulcers are responsible for more than half of all lower extremity ulceration... more Background-Venous leg ulcers are responsible for more than half of all lower extremity ulcerations. Significant interest has been focused on understanding the physiologic basis upon which patients fail to heal with standard therapy. Objective-This study uses complementary DNA microarray analysis of tissue samples from healing and non-healing venous leg ulcers to identify the genetic expression profiles from these dichotomous populations. Methods-Ulcer size and chronicity, factors that have been identified as prognostic indicators for healing, were used to distribute venous leg ulcers as healing versus non-healing. Punch biopsy samples were obtained from the wound edge and wound bed of all venous leg ulcers. The top fifteen genes with differential expression greater than twofold between the two populations of wounds (p < 0.05) were reported. Results-Significant differences were demonstrated in the expression of a diverse collection of genes, with particular differences demonstrated by genes coding for structural epidermal proteins, genes associated with hyperproliferation and tissue injury, as well as transcription factors.

Archives of Dermatology, 2007

To investigate the use of a topical oxygen emulsion (TOE), consisting of a supersaturated oxygen ... more To investigate the use of a topical oxygen emulsion (TOE), consisting of a supersaturated oxygen suspension using perfluorocarbon components, on second-degree burns and partial-thickness wounds. Design: Oxygen is a required substance for various aspects of wound repair, and increased oxygen tension in a wound has been shown to stimulate phagocytosis and to reduce the incidence of wound infection. Second-degree burns and partial-thickness wounds were created on the backs of specific pathogen-free pigs. Wounds were then randomly assigned to 1 of the following treatment groups: TOE, TOE vehicle, or air-exposed control. Main Outcome Measure: Wounds were assessed for complete epithelialization using a salt-split technique. Results: The TOE was able to significantly (P =.001) enhance the rate of epithelialization compared with both vehicle and untreated control. These data suggest that topical oxygen may be beneficial for acute and burn wounds. Conclusions: The results obtained from this doubleblind, control, in vivo study demonstrate that TOE can significantly enhance the rate of epithelialization of partialthickness excisional wounds and second-degree burns. These findings could have considerable clinical implications for patients with surgical and burn wounds by providing functional skin at an earlier date to act as a barrier against environmental factors, such as bacteria invasion. Other types of wounds may also benefit from this therapy (eg, chronic wounds and surgical incisions). Additional studies, including clinical studies, are warranted.

The Journal of Dermatologic Surgery and Oncology, 1992

A recent hypothesis suggests that venous hypertension leads to ulceration through the formation o... more A recent hypothesis suggests that venous hypertension leads to ulceration through the formation of pericapillay 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 pericapillay 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, pericapillay fibrin cuffs were detected in 20 (910/0) 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 recovey time, and transcutaneous oxygen measurements CcPOJ 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 pericapillay fibrin at 60 and 120 days. Although a reduction (mean f SD = 50.2% k 25.7) in ulcer size occurred in 10 of the 11 patients, pericapillay fibrin was still present at the ulcer edge and with undiminished intensity. We conclude that pericapillay 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. J Dermatol Surg Oncol 1992; 18~409-4 14. he pathogenesis of venous disease and ulceration remains unknown. It is generally accepted that the primary event is the develop

The Journal of Dermatologic Surgery and Oncology, 1992

A great deal of interest has been focused recently on the potential use of synthetic polypeptide ... more 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.

Journal of the American Academy of Dermatology, 1993

Background: Cutaneous manifestations of cryofibrinogenemia include purpura, ecchymosis, and ulcer... more Background: Cutaneous manifestations of cryofibrinogenemia include purpura, ecchymosis, and ulcerations. The histology of these lesions is characterized by intravascular thrombi. Objective: Our purpose was to test the efficacy of stanozolol, a drug capable of fibrinolytic enhancement, in treating cutaneous ulcers caused by cryotlbrinogenemia. Methods: Eight patients with cutaneous ulcerations from cryotlbrinogenemia were treated with stanozolol. Plasma cryofibrinogen was measured before and during treatment with stanozoloL Histologic evaluation was also performed before treatment and in selected patients during treatment. Results: After treatment, seven of the eight patients had healing of their ulcers, prompt reduction in their pain, and improvement in livedo reticularis and purpura. Four of the eight patients had no detectable plasma cryofibrinogen after treatment. In addition, dermal intravascular thrombi resolved. Stanozolol was well tolerated and had minimal side effects. Conclusion: We conclude that stanozolol is a safe and effective treatment of the cutaneous manifestations of cryofibrinogenemia.

Journal of the American Academy of Dermatology, 1991

Archives of Dermatology, 2010

Archives of …, 1997

Subjectsand Methods. Nine patients, aged35 to 81 years, with clinically diagnosedsmall plaque pso... more Subjectsand Methods. Nine patients, aged35 to 81 years, with clinically diagnosedsmall plaque psoriasis (plaque sizes 0-5 cm) consented to participate in this study. Two plaques of approximately the same size and severity, in symmetrical areas of the body, were randomly assigned as ...

British Journal of Dermatology, 1996

Initially thought to act as tissue replacement, cultured epithelial allografts are now known to w... more Initially thought to act as tissue replacement, cultured epithelial allografts are now known to work by providing a potent stimulus for healing. In i\ similar iashion. we believe Ihal traditional autografts may also provide a stimulus to help heal chronic wounds, thus acting as pharmacological agents for healing. We attempted to assess the possibility of augmenting Ihe stimulatory properties of donor skin by initiating the healing process in the donor region prior to grafting. This was accomplished hy pre-wounding the donor area 5 days prior to harvesting the donor skin. We compared these *pre-wounded' grafts to those harvested immediately. Two patients underwent punch grafting ibr chronic leg ulceration. Halfof the ulcer was grafted with donor skin harvested from an area that was pre-wounded and the other half from freshly harvested skin. We evaluated each ibr improvement of granulation tissue and degree of edge effect (migration of the previously dormant wound edges). All the grafts did well. There was marked improvement in granulation tissue in the ulcer bed after grafting, and the obvious presence of an edge effect. The edge effect was increased on the site where the pre-wounded graits were placed. It may be possible to augmenl the growth stimulatory properties of donor skin. This may offer therapeutic options in patients with chronic wounds.

Journal of the American Academy of Dermatology, 1993

Background: Cutaneous manifestations of cryofibrinogenemia include purpura, ecchymosis, and ulcer... more Background: Cutaneous manifestations of cryofibrinogenemia include purpura, ecchymosis, and ulcerations. The histology of these lesions is characterized by intravascular thrombi.

Archives of Dermatology, 2011

Archives of Dermatology, 1999

Background: Inherited epidermolysis bullosa (EB) is a mechanobullous disorder. The Dowling-Meara ... more Background: Inherited epidermolysis bullosa (EB) is a mechanobullous disorder. The Dowling-Meara variant, a subtype of EB, is characterized by widespread blister formation that may include the oral cavity and nails. Many patients with the Dowling-Meara phenotype are at increased risk of sepsis and death during infancy. The treatment of EB is generally supportive. The tissue-engineered skin used (Apligraf) is a bilayered human skin equivalent developed from foreskin. It is the only Food and Drug Administration-approved skin equivalent of its kind. It is approved for the treatment of venous ulcers of the lower extremities. It has also been used to treat acute wounds, such as graft donor sites and cancer excision sites.

Journal of Investigative Dermatology, 1999

Dermatologic Clinics, 2005

Cyanoacrylates (CAs), first produced in 1949 [1], are liquids that polymerize in the presence of ... more Cyanoacrylates (CAs), first produced in 1949 [1], are liquids that polymerize in the presence of moisture to form adhesives, glues, and films. The surgical use of these compounds was first proposed by Coover et al [2] in 1959. The short-chain cyanoacrylates (methyl, ethyl) [3,4] proved to be extremely toxic to tissue, however, preventing their widespread use as tissue glues. The short-chain CAs are used in nonmedical products, such as Krazy glue (Elmer's, Columbus, Ohio), and although they are not intended for medical use, dermatologists have been quoted in the popular press as recommending these glues for the treatment of fissures on fingers and toes [5]. Butyl cyanoacrylate (BCA), an intermediate-length CA, is not toxic when applied topically. Although it is not approved by the US Food and Drug Administration (FDA) for use in the United States, it has been used in Europe and Canada for middle ear procedures, to close cerebrospinal leaks, to repair incisions and lacerations, and to affix skin grafts [6-12]. Recently, a longer chain CA, octyl-2-cyanoacrylate (2-OCA), has been approved by the FDA and is now marketed (Dermabond topical skin adhesive) for closure of lacerations and incisions in place of sutures or staples. Even more recently, a 2-OCA formulated for greater flexibility, Liquid Bandage, has been approved for use in the over-the-counter market in the United States for the treatment of minor cuts and abrasions. This article discusses the use of CAs for their original cutaneous use as glues for the repair of lacerations and incisions and for their more recent use as films for use as dressings in the treatment of abrasions and wounds.

Journal of the American Academy of Dermatology, 2008

Background-Venous leg ulcers are responsible for more than half of all lower extremity ulceration... more Background-Venous leg ulcers are responsible for more than half of all lower extremity ulcerations. Significant interest has been focused on understanding the physiologic basis upon which patients fail to heal with standard therapy. Objective-This study uses complementary DNA microarray analysis of tissue samples from healing and non-healing venous leg ulcers to identify the genetic expression profiles from these dichotomous populations. Methods-Ulcer size and chronicity, factors that have been identified as prognostic indicators for healing, were used to distribute venous leg ulcers as healing versus non-healing. Punch biopsy samples were obtained from the wound edge and wound bed of all venous leg ulcers. The top fifteen genes with differential expression greater than twofold between the two populations of wounds (p < 0.05) were reported. Results-Significant differences were demonstrated in the expression of a diverse collection of genes, with particular differences demonstrated by genes coding for structural epidermal proteins, genes associated with hyperproliferation and tissue injury, as well as transcription factors.

Archives of Dermatology, 2007

To investigate the use of a topical oxygen emulsion (TOE), consisting of a supersaturated oxygen ... more To investigate the use of a topical oxygen emulsion (TOE), consisting of a supersaturated oxygen suspension using perfluorocarbon components, on second-degree burns and partial-thickness wounds. Design: Oxygen is a required substance for various aspects of wound repair, and increased oxygen tension in a wound has been shown to stimulate phagocytosis and to reduce the incidence of wound infection. Second-degree burns and partial-thickness wounds were created on the backs of specific pathogen-free pigs. Wounds were then randomly assigned to 1 of the following treatment groups: TOE, TOE vehicle, or air-exposed control. Main Outcome Measure: Wounds were assessed for complete epithelialization using a salt-split technique. Results: The TOE was able to significantly (P =.001) enhance the rate of epithelialization compared with both vehicle and untreated control. These data suggest that topical oxygen may be beneficial for acute and burn wounds. Conclusions: The results obtained from this doubleblind, control, in vivo study demonstrate that TOE can significantly enhance the rate of epithelialization of partialthickness excisional wounds and second-degree burns. These findings could have considerable clinical implications for patients with surgical and burn wounds by providing functional skin at an earlier date to act as a barrier against environmental factors, such as bacteria invasion. Other types of wounds may also benefit from this therapy (eg, chronic wounds and surgical incisions). Additional studies, including clinical studies, are warranted.

The Journal of Dermatologic Surgery and Oncology, 1992

A recent hypothesis suggests that venous hypertension leads to ulceration through the formation o... more A recent hypothesis suggests that venous hypertension leads to ulceration through the formation of pericapillay 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 pericapillay 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, pericapillay fibrin cuffs were detected in 20 (910/0) 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 recovey time, and transcutaneous oxygen measurements CcPOJ 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 pericapillay fibrin at 60 and 120 days. Although a reduction (mean f SD = 50.2% k 25.7) in ulcer size occurred in 10 of the 11 patients, pericapillay fibrin was still present at the ulcer edge and with undiminished intensity. We conclude that pericapillay 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. J Dermatol Surg Oncol 1992; 18~409-4 14. he pathogenesis of venous disease and ulceration remains unknown. It is generally accepted that the primary event is the develop

The Journal of Dermatologic Surgery and Oncology, 1992

A great deal of interest has been focused recently on the potential use of synthetic polypeptide ... more 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.

Journal of the American Academy of Dermatology, 1993

Background: Cutaneous manifestations of cryofibrinogenemia include purpura, ecchymosis, and ulcer... more Background: Cutaneous manifestations of cryofibrinogenemia include purpura, ecchymosis, and ulcerations. The histology of these lesions is characterized by intravascular thrombi. Objective: Our purpose was to test the efficacy of stanozolol, a drug capable of fibrinolytic enhancement, in treating cutaneous ulcers caused by cryotlbrinogenemia. Methods: Eight patients with cutaneous ulcerations from cryotlbrinogenemia were treated with stanozolol. Plasma cryofibrinogen was measured before and during treatment with stanozoloL Histologic evaluation was also performed before treatment and in selected patients during treatment. Results: After treatment, seven of the eight patients had healing of their ulcers, prompt reduction in their pain, and improvement in livedo reticularis and purpura. Four of the eight patients had no detectable plasma cryofibrinogen after treatment. In addition, dermal intravascular thrombi resolved. Stanozolol was well tolerated and had minimal side effects. Conclusion: We conclude that stanozolol is a safe and effective treatment of the cutaneous manifestations of cryofibrinogenemia.

Journal of the American Academy of Dermatology, 1991

Archives of Dermatology, 2010

Archives of …, 1997

Subjectsand Methods. Nine patients, aged35 to 81 years, with clinically diagnosedsmall plaque pso... more Subjectsand Methods. Nine patients, aged35 to 81 years, with clinically diagnosedsmall plaque psoriasis (plaque sizes 0-5 cm) consented to participate in this study. Two plaques of approximately the same size and severity, in symmetrical areas of the body, were randomly assigned as ...

British Journal of Dermatology, 1996

Initially thought to act as tissue replacement, cultured epithelial allografts are now known to w... more Initially thought to act as tissue replacement, cultured epithelial allografts are now known to work by providing a potent stimulus for healing. In i\ similar iashion. we believe Ihal traditional autografts may also provide a stimulus to help heal chronic wounds, thus acting as pharmacological agents for healing. We attempted to assess the possibility of augmenting Ihe stimulatory properties of donor skin by initiating the healing process in the donor region prior to grafting. This was accomplished hy pre-wounding the donor area 5 days prior to harvesting the donor skin. We compared these *pre-wounded' grafts to those harvested immediately. Two patients underwent punch grafting ibr chronic leg ulceration. Halfof the ulcer was grafted with donor skin harvested from an area that was pre-wounded and the other half from freshly harvested skin. We evaluated each ibr improvement of granulation tissue and degree of edge effect (migration of the previously dormant wound edges). All the grafts did well. There was marked improvement in granulation tissue in the ulcer bed after grafting, and the obvious presence of an edge effect. The edge effect was increased on the site where the pre-wounded graits were placed. It may be possible to augmenl the growth stimulatory properties of donor skin. This may offer therapeutic options in patients with chronic wounds.

Journal of the American Academy of Dermatology, 1993

Background: Cutaneous manifestations of cryofibrinogenemia include purpura, ecchymosis, and ulcer... more Background: Cutaneous manifestations of cryofibrinogenemia include purpura, ecchymosis, and ulcerations. The histology of these lesions is characterized by intravascular thrombi.