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Biomedical subjects

Loren H Engrav

Publications and source records attributed to Loren H Engrav.

At least 19 recordsLinked to original sources

Histology of the thick scar on the female, red Duroc pig: final similarities to human hypertrophic scar.

The etiology and treatment of hypertrophic scar remain puzzles even after decades of research. A significant reason is the lack of an accepted animal model of the process. The female, red Duroc pig model was described long ago. Since the skin of the pig is similar to that of humans, we are attempting to validate this model and found it to be encouraging. In this project we quantified myofibroblasts, mast cells and collagen nodules in the thick scar of the Duroc pig and compared these to the values for human hypertrophic scar. We found the results to be quite similar and so further validated the model. In addition, we observed that soon after wounding an inflammatory cell layer forms. The thickness of the inflammatory layer approaches the thickness of the skin removed as if the remaining dermis "knows" how much dermis is gone. In deep wounds this inflammatory layer thickens and this thickness is predictive of the thickness of the ultimate scar.

Adolescent↗

Incidence and characteristics of hospitalized patients with pressure ulcers: State of Washington, 1987 to 2000.

BACKGROUND: Pressure ulcers complicate the hospital course of critically injured or ill patients. Guidelines have been promulgated to prevent pressure ulcers in hospitalized patients. The purpose of this study was to determine whether these guidelines have, in fact, reduced the incidence of pressure sores. METHODS: The authors examined census data from the National Center for Health Statistics and the Washington State Department of Health for the 14-year period 1987 through 2000 and identified patients with a pressure ulcer listed as the primary diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 707.0) and patients admitted for other diagnoses with pressure ulcer as a secondary diagnosis. The authors reasoned that patients who were admitted for treatment of pressure ulcers would have the diagnosis listed as primary, whereas those who were admitted for other reasons and developed pressure ulcers during the admission would have pressure ulcer listed as a secondary diagnosis. Other available data included patient age, sex, procedures for pressure ulcers (International Classification of Diseases, Ninth Revision, Clinical Modification codes 15920 through 15999), length of stay, and hospital charges for care. RESULTS: The incidence of pressure ulcers as a primary diagnosis varied from 7.0 to 8.3 per 100,000 population but did not change over the 14-year study period. The rate of operation for these ulcers also did not change. The incidence of pressure ulcers as either a primary or secondary diagnosis doubled from 34.5 to 71.6 per 100,000 (p < 0.001), whereas the incidence of operative procedures for these ulcers did not change. CONCLUSION: The authors found no evidence that the guidelines for the prevention of pressure ulcers have been effective in decreasing pressure ulcer formation, but it may be that pressure ulcers are now being reported in a more thorough manner.

Adult↗

Complex wound management utilizing an artificial dermal matrix.

The benefits of the Integra Dermal Regeneration Template in the management of extensive burn injuries have been well documented. Integra can reduce donor- and graft-site scarring and has been reported to be capable of vascularizing over small areas of exposed bone and tendon. Given these potential advantages, we have used Integra for a variety of other reconstruction applications. We performed a retrospective review of patients with complex wounds treated with Integra at our burn center. Integra was used in the management of a variety of wounds, including necrotizing fasciitis, extremity degloving injury, meningococcemia, Marjolin ulcer, postburn lip reconstruction, and fourth-degree burns with exposed bone or tendon. Engraftment rates of Integra and autograft were 98% +/- 4% and 97% +/- 4%, respectively. All areas of graft loss healed without need for regrafting. The benefits of Integra in the management of acute burn wounds can be extended to other traumatic and complex wounds.

Adolescent↗

Correlation of clinical outcome of integra application with microbiologic and pathological biopsies.

BACKGROUND: Integra, a dermal replacement template consisting of bovine collagen, chondroitin-6-sulfate, and a silastic sheet is a postexcisional treatment for deep partial to full thickness burns where autograft is limited. This study correlates Integra histology and quantitative microbiology cultures with clinical outcomes after autografting. METHODS: Charts of 29 burn patients who underwent Integra treatment and neodermis biopsy at the time of ultra thin autografting were reviewed. We analyzed microbial contamination, inflammatory reaction, and autograft take. RESULTS: The mean burn size and age were 43% total body surface area and 39 years old, respectively. In quantitative neodermis cultures, 90% of samples had bacterial growth; nine samples (31%) had > 10(5) colony forming units per gram. The most common organism was Staphylococcus aureus (31%). Patients with quantitative bacterial counts >10(5) CFU/g received targeted systemic antibiotics. Integra take (83%) and autograft take (92%) were acceptable even in patients with high bacterial counts (78% Integra take; 86% autograft take). More than 50% of biopsies had dermal regeneration similar to normal dermis; foreign body reactions were unusual. Histologic evidence of inflammation, especially polymorphonuclear cells, was increased in biopsies with high bacterial counts. CONCLUSION: Integra and autograft take can be acceptable even with high bacterial counts if wounds are treated with appropriate targeted topical and systemic antibiotics in the presence of microbial contamination. Neodermis biopsies showed fibrous in-growth congruent with existing Integra fibers with minimal foreign body reaction. These data support Integra use as a safe and effective treatment modality in patients with major burns.

Administration, Topical↗

Elevated orbital pressure: another untoward effect of massive resuscitation after burn injury.

BACKGROUND: Fluid resuscitation remains a fundamental component of early burn care management. However, recent studies suggest that excessive volumes of resuscitation are being administered. Overresuscitation results in negative sequelae including abdominal and extremity compartment syndromes. Elevated intraocular pressure (IOP) has been described as another potentially devastating effect of massive fluid resuscitation in trauma patients. The orbit, similar to the abdomen and extremity, is a compartment, limited to expansion from edema anteriorly by the eyelids and orbital septum, and posteriorly by the bony orbital walls. The purpose of this study was to review the incidence of elevated IOP in a series of patients with major burn injury. METHODS: We retrospectively reviewed the charts of 13 consecutive patients admitted to our burn center with burn sizes >25% total body surface area (TBSA). All patients underwent serial IOP measurements for the first 72 hours following admission. Medical records were reviewed for fluid resuscitation volume, IOP measurements, need for canthotomy, and results of canthotomy procedures. RESULTS: Five of 13 patients had IOP >30 mm Hg and required lateral canthotomy. Canthotomy immediately reduced IOP (p = 0.009). Patients who developed elevated IOP received a significantly larger fluid resuscitation (9.0 cc/kg/%TBSA versus 6.0 cc/kg/%TBSA, p = 0.02). Elevated IOP was significantly associated with delivery of larger fluid resuscitation volume (p = 0.027). CONCLUSIONS: Massive fluid resuscitation following burn injury can result in orbital compartment syndrome requiring lateral canthotomy. Early diagnosis and treatment of orbital compartment syndrome should be incorporated into the management of patients with major burn injury receiving large fluid resuscitation volume.

Adult↗

Changes in VEGF and nitric oxide after deep dermal injury in the female, red Duroc pig-further similarities between female, Duroc scar and human hypertrophic scar.

Despite decades of research, our understanding of human hypertrophic scar is limited. A reliable animal model could significantly increase our understanding. We previously confirmed similarities between scarring in the female, red, Duroc pig and human hypertrophic scarring. The purpose of this study was to: (1) measure vascular endothelial growth factor (VEGF) and nitric oxide (NO) levels in wounds on the female Duroc; and (2) to compare the NO levels to those reported for human hypertrophic scar. Shallow and deep wounds were created on four female Durocs. VEGF levels were measured using ELISA and NO levels with the Griess reagent. VEGF and NO levels were increased in deep wounds at 10 days when compared to shallow wounds (p < 0.05). At 15 weeks, VEGF and NO levels had returned to the level of shallow wounds. At 21 weeks, VEGF and NO levels had declined below baseline levels in deep wounds and the NO levels were significantly lower (p < 0.01). We found that VEGF and NO exhibit two distinctly different temporal patterns in shallow and deep wounds on the female Durocs. Furthermore, NO is decreased in female, Duroc scar as it is in human, hypertrophic scar further validating the usefulness of the model.

Animals↗

Management of facial burns with a collagen/glycosaminoglycan skin substitute-prospective experience with 12 consecutive patients with large, deep facial burns.

Management of deep facial burns remains one of the greatest challenges in burn care. We have developed a protocol over the past 20 years for management of facial burns that includes excision and coverage with thick autograft. However, the results were not perfect. Deformities of the eyelids, nose and mouth as well as the prominence of skin graft junctures demonstrated the need to explore novel approaches. Integra has been used with success in the management of burns of the trunk and extremities. The purpose of this study was to prospectively evaluate the aesthetic outcome of the use of Integra for deep facial burns. Twelve consecutive patients underwent excision of large, deep facial burns and placement of Integra. Integra provides excellent color and minimally visible skin graft junctures. The texture is good but not as supple as thick autograft. Integra is not well suited for use in the coverage of eyelid burns due to the need to wait 2 weeks for adequate vascularization. In summary, thick autograft remains the gold standard for deep facial burns. However, for patients with extensive burns and limited donor sites, Integra provides an acceptable alternative.

Adult↗

Patterns of grease burn injury: development of a classification system.

Grease burns occur commonly in the home during food preparation. It has been our observation that grease burns follow a particular pattern of injury. The purpose of this study was to review our institutional experience in the management of these burns to develop a classification scheme. We performed a retrospective review of patients admitted to our burn center with grease burns. Subjects were identified through our database and their charts were reviewed with particular attention to burn distribution, TBSA and need for grafting. We excluded workplace burns and children under the age of six. A total of 249 patients who fit the above criteria were admitted with grease burns to our burn center from 1993 to 2003. The sequence of events leading to burn and its distribution followed a consistent pattern. The majority of patients (86%) had an isolated upper extremity burn or upper extremity burn in combination with a face, trunk or lower extremity burn. Forty percent of patients required at least one excision and grafting procedure. Grease burns associated with cooking at home follow predictable patterns of injury. Based on these patterns we proposed a classification system for domestic grease burns.

Accidental Falls↗

Substance P levels and neutral endopeptidase activity in acute burn wounds and hypertrophic scar.

BACKGROUND: Substance P, a cutaneous neuroinflammatory mediator released from peripheral nerves, plays a role in responses to injury. Neutral endopeptidase is a cell membrane-bound metallopeptidase enzyme that regulates substance P activity. The question of substance P involvement in hypertrophic scar development has been based on observations that hypertrophic scars have increased numbers of nerves. The authors hypothesized that hypertrophic scar has greater substance P levels and decreased neutral endopeptidase activity compared with uninjured skin and acute partial-thickness burns, which may contribute to an exuberant response to injury. METHODS: The authors obtained small skin samples of deep partial-thickness burns (n = 7; postburn days 7 to 78) and uninjured skin (n = 14) from patients (eight male patients and six female patients; 2 to 71 years old) undergoing burn wound excision. Hypertrophic scar samples were obtained from six patients (three male patients and three female patients; 8 to 47 years old) undergoing surgical excision 13 to 64 months after burn injury. Protein concentrations were determined using a bicinchoninic acid assay. Substance P concentration was determined by means of indirect enzyme-linked immunosorbent assay. Neutral endopeptidase activity was measured using an enzymatic assay that quantifies a fluorescent degradation product, methoxy-2-naphthylamine (MNA). Substance P and neutral endopeptidase data were standardized to sample weight. RESULTS: Substance P levels were greater in hypertrophic scar (3506 pg/g) compared with uninjured skin (1698 pg/g; p < 0.03) and burned skin (958 pg/g; p < 0.01). Hypertrophic scar samples had decreased neutral endopeptidase enzyme activity (8.8 pM MNA/hour/microg) compared with normal skin (16.3 pM MNA/hour/microg; p < 0.05). Acute burn wounds (27.9 pM MNA/hour/microg) demonstrated increased neutral endopeptidase enzyme activity (p < 0.05). CONCLUSIONS: Increased substance P concentration in hypertrophic scar correlates with histologic findings of increased nerve numbers in hypertrophic scar samples. Decreased neutral endopeptidase enzyme activity in hypertrophic scar may contribute to increased available substance P that may result in an exuberant neuroinflammatory response.

Adolescent↗

Nerve quantification in female red Duroc pig (FRDP) scar compared to human hypertrophic scar.

A significant impediment to studying hypertrophic scar is the lack of an animal model. We have confirmed similarities between scarring in the female red Duroc pig (FRDP) and human hypertrophic scar and conclude that this model warrants validation. Reports have suggested that the cutaneous nervous system may play a role in hypertrophic scar development and several studies have shown nerve density in hypertrophic scar to be increased. The purpose of this study was to further validate the FRDP model of hypertrophic scar by quantifying nerves in FRDP tissue and comparing the findings to human hypertrophic scar. Wounds of varying depth were created on the backs of two FRDP and tissue samples were harvested at 10 days, 1 month and 5 months post-wounding. Human specimens were obtained from six burn patients. Immunohistochemistry was performed and digital images were captured. Color subtractive computer-assisted image analysis was used to quantify nerve density and nerve area fraction. The results demonstrate that nerve tissue is increased in FRDP scar tissue and is quite similar to that in human hypertrophic scar and to that described in the literature. These data provide additional evidence that the FRDP model may be useful for studying hypertrophic scarring.

Adolescent↗

Is supra-Baxter resuscitation in burn patients a new phenomenon?

Baxter described the use of 4 cm3/kg/%TBSA as a guideline for fluid resuscitation after burns. However, recent studies have shown that, at the present time, patients generally receive greater than the "Baxter" formula. Pruitt has called this phenomenon "fluid creep," and it has the potential for significant consequences including abdominal and extremity compartment syndromes and severe pulmonary insults. The purpose of this paper is to determine if this supra-Baxter resuscitation is a new phenomenon. We performed a retrospective chart review with two cohorts of patients. Group 1 consisted of 11 patients admitted between 1975 and 1978 to our burn center. Group 2 consisted of 11 patients admitted to our burn center in 2000 who were matched for age, sex, and percent total body surface area burned. Group 1 received 3.6 +/- 1.1 cm3/kg/% TBSA of fluid in the first 24 h. Group 2 received 8.0 +/- 2.5 cm3/kg/% TBSA, which is 100% more than the Baxter formula. There was no difference in the median age, weight, or 24-h urine output between the two groups. Our data demonstrate that the "fluid creep" phenomenon is relatively new.

Adolescent↗

Further similarities between cutaneous scarring in the female, red Duroc pig and human hypertrophic scarring.

Knowledge of the pathophysiology of hypertrophic scarring following deep dermal injuries is minimal due to the lack of an animal model. We previously confirmed that thick scars in female, red Duroc pigs (FRDP) are similar to human hypertrophic scar. The purpose of this study was to evaluate TGFbeta1, IGF-1, decorin, and versican expression in FRDP wounds. Deep and shallow wounds on the backs of two FRDPs were studied over 5 months. Immunohistochemistry was performed for TGFbeta1, IGF-1, decorin, and versican. TGFbeta1 and IGF-1 mRNA were evaluated by in situ hybridization and RT-PCR. In shallow wounds (1) TGFbeta1 protein was not detectable and IGF-1 protein was seen at 10 days post-wounding. TGFbeta1 and IGF-1 mRNA were elevated for 30 days. (2) Decorin protein was not detected at 10th day, but returned to levels of uninjured skin. (3) Versican protein was not detectable at any time. In deep wounds, (1) TGFbeta1 and IGF-1 protein and mRNA were elevated early, (2) decorin protein was greatly reduced for the first 90 days, and (3) versican protein was present from 30 to 150 days. These findings correlate with findings reported in the literature for human hypertrophic scar and further validate the FRDP model of hypertrophic scarring.

Animals↗

"Opioid creep" is real and may be the cause of "fluid creep".

Recent studies have shown that burn patients receive larger volumes of fluids than predicted by the Baxter formula and the reason for this is unclear. One potential reason is that increased analgesics are used which could blunt the response to fluid resuscitation. The purpose of this study was to compare the administration of opioid agonists in patients treated at a single burn center in the 1970s and in the year 2000. We performed a retrospective chart review comparing two matched cohorts. Group I consisted of 11 patients admitted between 1975 and 1978. Group II consisted of 11 patients admitted in 2000 matched for age, sex and %TBSA. Patients in Group II received a significantly higher mean opioid equivalent than those in Group I (26.5 +/- 12.3 versus 3.9 +/- 2.2 in the first 24h, P < 0.001). In addition, in Group II, a larger variety and combination of opioid agonists were used. This review demonstrates a significant increase from the 1970s to 2000 in the type, dose prescribed and dose delivered of opioid agonists. Along with "fluid creep", we have also increased our use of opioid agonists or "opioid creep". Higher doses of opioid agonists may have hemodynamic consequences, which may contribute to the increased fluid volumes.

Adolescent↗

Meshed unexpanded split-thickness skin grafting for reconstruction of penile skin loss.

PURPOSE: Sheets of unmeshed, split-thickness skin grafts (STSGs) have been advocated in potent men with penile skin deficiency. Since the survival of sheet grafts is rarely 100% and the appearance of unexpanded 1:1 mesh grafts is quite good, we used this technique. We report our experience with meshed, unexpanded STSGs for all penile resurfacing regardless of erectile function. MATERIALS AND METHODS: Nine consecutive patients with penile skin loss were prospectively treated between March 2001 and January 2003 with meshed STSGs to the penis. The underlying condition was Fournier's gangrene in 4 cases, chronic lymphedema in 2, skin deficiency from prior surgeries in 2 and Crohn's disease in 1. Graft thickness was 0.012 or 0.016 inches and meshing was performed in a 1:1 ratio. Meshed slits were oriented transversely without expansion and the graft juncture was located on the ventral surface in zigzag fashion. Graft take, appearance, and sexual and voiding function were assessed postoperatively. RESULTS: All 9 patients had 100% graft take. At a mean followup of 6 months a satisfactory cosmetic outcome was documented photographically in all except 1 case involving chronic penile manipulation. Erectile function and ejaculation were preserved in potent patients. CONCLUSIONS: Unexpanded meshed STSGs of penile skin loss yielded satisfactory functional and cosmetic outcomes.

Adult↗

What is the prevalence of hypertrophic scarring following burns?

Hypertrophic scarring after burns remains a major problem and is considered to be "common". Pressure garments are commonly used as treatment even though there is little sound data that they reduce the prevalence or magnitude of the scarring. In 1999 we began a study of the efficacy of pressure garments on forearm burns. After studying 30 patients, mainly white adults, we found no hypertrophic scar in either those treated with pressure or without. This prompted us to review the literature on the prevalence of hypertrophic scarring after burns and found only four articles with a relatively small number of patients and only three geographical locations. It became clear that the prevalence of hypertrophic scarring is really unknown. We then did a retrospective study of 110 burn survivors and counted all hypertrophic scars of all sizes and locations in all races and found the prevalence hypertrophic scarring to be 67% which conflicts with the published reports and our prospective study and suggests that further research is necessary. We concluded that a worldwide, prospective survey is necessary to establish the prevalence of hypertrophic scarring after burns. In this article we are calling for and offering to organize this survey.

Adolescent↗

The female, red Duroc pig as an animal model of hypertrophic scarring and the potential role of the cones of skin.

Hypertrophic scarring occurs after deep dermal wounds. Our understanding of the etiology is poor; one reason is the lack of an animal model. In 1972, Silverstein described scarring in the Duroc pig but the model was never confirmed nor disproved. Another reason, as we previously suggested, is that hypertrophic scarring only occurs within regions of human skin that contain cones and the cones have not been studied in relation to hypertrophic scarring. We, therefore (i) explored healing in the female, red Duroc model for similarities to human hypertrophic scarring, studying wound thickness, appearance, healing status at 3 weeks, histology, and immunocytochemical localization of decorin, versican, TGFbeta1 and IGF-1; and (ii) examined Duroc skin for cones. We found that healing after deep wounds in Duroc pigs is similar, but not identical, to human hypertrophic scarring. We also found that Duroc skin contains cones. Healing in the female, red Duroc pig is sufficiently similar to human hypertrophic scarring to warrant further study so that it can be accepted or rejected as a model of human hypertrophic scarring. In addition, the relationship of the cones to hypertrophic scarring needs further detail and can be studied in this model.

Animals↗

Early excision and grafting of face and neck burns in patients over 20 years.

Although excision and grafting of burns has become common and standard, many surgeons have been reluctant to excise and graft face burns. In fact, we could find photographic results at 1 year after grafting of only eight patients in the English literature. We began excision and grafting of face burns in 1979 and presented our first 16 patients in 1986 in this journal. With encouragement from Janzekovic and Jackson, we continued and have now used essentially the same procedure for more than 20 years in approximately 100 patients and, from this large series, are able to present outcomes. From January of 1979 to May of 1999, we performed excision and grafting on 91 patients with deep face burns. Data were recorded and 35-mm photographs were obtained throughout the 20-year period. We reviewed that database and the slide files of these patients. We found 45 patients with complete photographic sets including 1-year follow-up. Since, in our opinion, there is no useful, objective measure of appearance, we decided to simply publish all 45 sets of complete photographs, permitting the reader to subjectively form an opinion of the outcome of this procedure. The results are all shown as "full" face burns and two "partial" face burns. We continue to believe that early excision and grafting is indicated for face burns that will not heal within 3 weeks and that the procedure yields results that permit the burn victims to return to society and minimizes the time off work or out of school.

Burns↗