Then and now: studies using a burned mouse model reflect trends in burn research over the past 25 years.
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Animals↗
Biomedical subjects
G D Warden
Publications and source records attributed to G D Warden.
Computer keyboards as reservoirs for Acinetobacter baumannii in a burn hospital.
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Acinetobacter↗
Reduction mammaplasty in postburn breasts.
Thermal injury to the anterior chest in the adolescent girl can lead to severe disfigurement of the breasts. Just as in certain non-burn female patients, mammary hyperplasia can occur in patients with previous full-thickness burns of their breasts. Most plastic surgeons have been reluctant to perform reduction mammaplasty in these patients for fear of devascularizing the skin graft or the nipple-areola complex. A series of six patients with full-thickness burns of the breasts and subsequent skin graft coverage before reduction mammaplasty is reported. Four patients had bilaterally burned breasts requiring reduction. Two patients had one burned breast reduced, and one required a balancing procedure on the unburned side. Reduction mammaplasty was performed using the inferior-pedicle technique. The mean amount of tissue removed for the left and right breasts was 454 and 395 g, respectively. There was no nipple loss, hematoma, infection, or major loss of skin flaps. Reduction mammaplasty in this group of patients is safe and carries minimal risk if certain key concepts are followed carefully.
Adolescent↗
The effect of full-thickness abdominal wall burns sustained during childhood on subsequent childbearing ability.
The effect of full-thickness burns of the abdomen during childhood on subsequent pregnancy was evaluated. Eight hundred female pediatric patients treated for acute burns during a 14-year period (1975-1989) at the Shriners Burns Institute were reviewed. Through a combination of clinical follow-up, questionnaires, or phone interviews, data were obtained regarding the histories of 31 pregnancies in 19 patients who had required excision and skin grafting of > or = 50% of their abdominal wall during management of their acute burns. These patients sustained a mean burn size of 59.8% total body surface area (TBSA; range, 23-87%) with a mean full-thickness burn of 43.8% TBSA (range, 10-78%). The mean age at the time of burn was 7.6 years (range, 1.5-15 years). Normal rates of vaginal and cesarean section deliveries, prematurity, and infant mortality were observed in these 31 pregnancies. Despite a subjective sensation of increased tension on the scar in 25% of the patients, no interference with these patients carrying a full-term pregnancy directly attributable to the burn scar was identified. Follow-up and examination during the third trimester of pregnancy demonstrated how the burned and unburned portion of the abdominal wall accommodated the enlarged uterus. This review demonstrates that after extensive burns to the abdomen, which have been treated with excision and skin grafting during childhood, the scarred abdominal wall accommodates full-term pregnancy without the need for surgical release.
Abdominal Injuries↗
Tissue expander complications in the pediatric burn patient.
Tissue expanders have become a useful adjuvant in pediatric burn reconstruction. We reviewed our experience with tissue expanders from June of 1984 to July of 1995. There were 403 expanders used in 301 patients. Complications relative to specific anatomic areas from July of 1987 to July of 1995 were compared with previously published data in the journal from June of 1984 to June of 1987. Complications were defined as absolute if they resulted in the loss of expanders or in additional surgery, or none of the preoperative plan was satisfied. The relative complications were defined as spotty alopecia, alopecia greater than 50 percent, or the operative plan was only partially satisfied, sometimes implying poor surgical judgment. The overall complication rate for the period June of 1984 to June of 1987 was 30 percent (37 complications in 122 expanders). In the July of 1987 to July of 1995 study, the complication rate was only 18 percent (51 complications in 281 expanders). This was a statistically significant decrease between the periods (p = 0.010). In the recent 8-year period, there was a decrease compared with the previous study in both the absolute and relative complications. The most common absolute complication in this period was infection (15 of 31, 48 percent) with 12 (39 percent) being early infection. With regard to the nine complications in the neck, face, ear, and supraclavicular area, two-thirds were related to leakage or exposure of the expanders, resulting from the tight anatomic area causing mechanical damage of the expanders as well as ischemia to the overlying skin. Early in the study, the lower extremities proved to involve difficult or unsatisfactory areas to expand, and lower extremity expansion was abandoned throughout the remainder of the study period. The overall decrease in absolute and relative complications is likely the result of increased operative experience as well as a developed protocol for the prevention of perioperative complications relating to infection and expansion in high-risk anatomic sites.
Burns↗
Scalp autografts and hair transfer to the face in the burned child.
Hair transfer from split-thickness skin grafts harvested from the scalp is not a widely reported problem. The authors present their experience with hair transfer from scalp autografts in a pediatric burn population, with particular emphasis on hair transfer to the face. They retrospectively reviewed 3307 acute and reconstructive pediatric burn admissions over a 4-year period at a single institution and identified 109 cases in which the scalp had been used as a donor site and in which the patient survived the acute burn period. Data from 73 male and 36 female patients were analyzed with respect to age, race, sex, percent total body surface area burned, graft thickness, number of scalp harvests and time between harvests, and presence of donor site alopecia. Eighteen of the 109 patients had noticeable hair growth from their scalp grafts (17 percent). Fourteen of 18 cases of hair growth involved face or neck grafts (13 percent); the remaining 4 patients had hair growth elsewhere on the body. There was no difference between the two groups (hair growth versus no hair growth) when compared by age, sex, or graft thickness. There was a correlation between larger burn size and greater incidence of hair growth. Those who had multiple harvests of the same scalp donor site were more than twice as likely to have hair transfer (9 of 34 versus 9 of 75 patients), although time between harvests was not a significant variable. Caucasian children represented 77 percent of the study population yet 100 percent of the cases of problem hair growth. Thirty-three percent of the hair growth group (6 of 18 patients) and 4 percent of the remaining patients (4 of 91) had some degree of donor site alopecia. The scalp is a reliable and valuable donor site for skin grafting in children, particularly for facial burns. The authors note a moderate incidence of hair transfer (17 percent) and propose both suggestions for prevention and recommendations for management.
Burns↗
Glutaraldehyde crosslinking of collagen substrates inhibits degradation in skin substitutes grafted to athymic mice.
Collagen-based implants have been described as vehicles for transplantation of cultured skin cells for treatment of burn wounds. To optimize vascularization and repair of connective tissue, collagen solubility and glutaraldehyde crosslinking were evaluated. Cultured skin substitutes consisted of human keratinocytes and fibroblasts attached to collagen-glycosaminoglycan substrates that were prepared from acid-insoluble, or partially soluble collagen. Substrates were crosslinked with 0% or 0.25% glutaraldehyde, populated with cells, and grafted to full-thickness wounds on athymic mice (n = 6/condition). After 6 weeks, the wound area was measured by planimetry, and healed wounds were scored by histochemistry for immunoreactivity to HLA-ABC and bovine collagen. Data analysis shows that crosslinking of collagen implants with glutaraldehyde is associated (p < 0.001) with detection of the implant. No association was found between solubility of bovine collagen and immunodetection. Epidermis of all wounds was positive for HLA-ABC, and no differences in wound areas were found. These results suggest that glutaraldehyde crosslinking of collagen implants decreases the rate of biodegradation. Delayed degradation of crosslinked collagen may result clinically in reduced engraftment of skin substitutes.
Animals↗
Neutrophils from burn patients are unable to increase the expression of CD11b/CD18 in response to inflammatory stimuli.
Neutrophils (PMNs) from patients with thermal injury are dysfunctional for the CD11b/CD18-dependent functions of diapedesis, chemotaxis, and phagocytosis. The expression of CD11b/CD18 on normal PMNs is increased after an inflammatory stimulus. We proposed that CD11b/CD18 expression on burn patient PMNs would respond abnormally to inflammatory stimuli. PMNs were obtained from nonseptic burn patients during the second week after thermal injury. PMNs from burn patients incubated with lipopolysaccharide (LPS), N-formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate, or A23187 did not increase the expression of CD11b/CD18 to the same degree exhibited by normal PMNs. This inability to increase CD11b/CD18 was not due to differences in CD14 receptor expression, LPS binding, or factors present in the serum of burn patients. The upregulation of CD35 also was decreased on burn patient PMNs. Western blot analysis revealed decreased quantities of CD11b protein in burn patient PMNs compared with normal control PMNs. The deficiency in CD11b/CD18 expression after inflammatory stimuli may explain some of the abnormalities observed in burn PMN function.
Burns↗
Lack of effect of sleep on energy expenditure and physiologic measures in critically ill burn patients.
OBJECTIVE: Energy expenditure measurements, performed while patients are in standardized resting conditions, are often used as an indicator of care by which to evaluate the adequacy of nutrition support regimens. Little attention has been directed toward examining potential errors incurred by deriving daily energy needs based on a single 15- to 20-minute measurement. This study was designed to differentiate energy expenditure during periods of sleep (defined as time spent in any of the standard sleep stages) and wakefulness in pediatric burn patients. DESIGN: Twenty-four-hour indirect calorimetry, polysomnography, and physiologic assessments (mean arterial pressure, heart rate, body temperature, oxygen saturation, and respiratory rate) were conducted simultaneously in 14 patients, who were thermally injured and tracheally intubated, for a total of 45 24-hour intervals. SUBJECTS: Mean age of the patients was 10.8+/-1.2 years. Mean total body surface area of the injury was 55.7+/-4.7%, and mean full-thickness burn was 48.8+/-6.0%. STATISTICAL ANALYSES PERFORMED: A nested general linear analysis of variance model was used to evaluate the association between sleep, wakefulness, and energy needs; adjustments were made for postburn day and multiple test runs per patient. RESULTS: On average, subjects slept 699+/-46 minutes/day. They experienced a large number of awakenings from sleep (mean=53+/-6.3 awakenings per 24 hours). Patients had mean energy expenditure of 2,529+/-396 kcal/day while awake and 2,360+/-291 kcal/day while asleep, and these mean values did not differ significantly. No differences in physiologic measurements during the awake and sleep states were found. APPLICATIONS: There appears to be little difference in the metabolism of seriously injured burn patients while asleep and while awake. The study deemphasizes the importance of performing indirect calorimetry at rest in critically ill pediatric burn patients, and it supports the extrapolation of daily energy expenditure from a 15- to 20-minute steady-state measurement obtained during either sleep or wakefulness.
Adolescent↗
Outpatient burn management.
The outpatient environment is appropriate for the management of many minor or moderate burn injuries. Ambulatory care moves across the continuum of recovery from treatment of the acute insult, through the rehabilitative phase of care, to surgical reconstruction. The patient and family actively participate with the multidisciplinary team in the design of a holistic plan of care. Ongoing evaluation of progress is provided to achieve optimal outcomes based on standards of care and standards of practice.
Ambulatory Care↗
Evaluation of predicted and measured energy requirements in burned children.
OBJECTIVE: The energy predictions of nine calculations for pediatric patients were compared with measured resting energy expenditure (MREE) by means of indirect calorimetry to determine the optimal means of energy projection in the burn population younger than 3 years of age. METHODOLOGY: Nutritional sufficiency and maintenance of preburn weight were factors in the confirmation of energy needs. Demographic factors were also studied: preburn weight, percent burn, percent third-degree burn, and age. Group 1 consisted of 24 patients younger than 3 years of age (range = 7 months to 2.6 years) with a percent burn of 30.6 +/- 2.0 and percent third-degree burn of 21.9 +/- 2.6. Group 2, consisting of 24 patients 5 to 10 years old matched by percent burn and percent third-degree burn, was included to determine whether differences between actual and projected needs were evident in older, prepubescent patients. STATISTICAL ANALYSIS: Analysis of variance was used to ascertain the most reliable multiplier for MREE needed to maintain at least 95% of preburn weight at discharge while ensuring adequate nutrition. Multiple regression analysis was used to determine the relationship between energy requirement and body weight, percent burn, and age. RESULTS: An additional 30% of MREE provided a consistent ratio of actual energy intake to required intake. MREE x 1.3 was used as a guide to study the existing calculations. For both groups, the four equations that predicted energy in healthy children most often underestimated MREE x 1.3, whereas the five formulas for children with burns tended to overpredict energy. Regression analysis yielded two new sets of equations using age, preburn weight, and percent burn (< 3 years = Mayes 1 [r2 = .71], 5 to 10 years = Mayes 3 [r2 = 70] or percent third-degree burn (< 3 years = Mayes 2 [r2 = .68], 5 to 10 years = Mayes 4 [r2 = .67]). CONCLUSIONS: The application of a 30% factor to MREE is supported in burn patients younger than 10 years of age. Standard energy projections do not provide an accurate assessment of energy needs in the pediatric burn population; thus, two sets of equations that more closely predict energy needs are proposed.
Analysis of Variance↗
Pigmentation and microanatomy of skin regenerated from composite grafts of cultured cells and biopolymers applied to full-thickness burn wounds.
Rapid coverage and epithelial closure of extensive burns remains a major requirement for patient recovery. Although many skin substitutes have been described, permanent regeneration of both epithelial and connective tissues after a single surgical application of a skin substitute has not become routine. To replace both dermal and epidermal skin, cultured skin substitutes (CSS) were prepared from autologous keratinocytes and fibroblasts seeded onto collagen-glycosaminoglycan (C-GAG) substrates. CSS were applied to excised, full-thickness burns on 5 patients. Histologic analysis showed a fully stratified, hyperkeratotic epidermis within 12 days of grafting with little to no evidence of an inflammatory reaction. Epidermal and connective tissues are interdigitated in analogy to rete pegs and dermal papillae, and the neovascular plexus approximates the dermal-epidermal junction. Transmission electron microscopy identified a continuous basement membrane with hemidesmosomes and anchoring fibrils that connected the epidermis with the underlying connective tissue. Within 14-28 days, the C-GAG had been degraded and replaced by newly synthesized collagen in regenerated connective tissue. Spontaneous repigmentation of healing CSS from passenger melanocytes in keratinocytes culture was observed within 2 months after grafting. Electron microscopy revealed the presence of numerous melanosomes within the keratinocytes, illustrating pigment transfer between melanocytes and keratinocytes after wound closure. These results demonstrate that the CSS develop into functional permanent skin tissue capable of spontaneous repigmentation after grafting onto burn wounds.
Adolescent↗
The use of extracorporeal life support in pediatric burn patients with respiratory failure.
Respiratory failure is the most common cause of death after thermal injury and may be caused by inhalation injury, acute respiratory distress syndrome (ARDS) or pneumonia. ARDS is usually associated with sepsis; however, it may also occur during burn shock, especially in patients that have a delayed or inadequate fluid resuscitation. During the past 24 months, five pediatric burn patients underwent extracorporeal life support (ECLS) for respiratory failure unresponsive to optimal medical management. The mean age of the patients was 26 months (range, 8.5 to 48 months), with a mean burn size of 46% TBSA (> 95% third degree). The etiology of the respiratory failure included severe bronchospasm in a 22-month-old former premature infant with bronchopulmonary dysplasia; three patients with ARDS; and one patient with a severe inhalation injury. All five patients required greater than 56 cm H2O peak pressures and 100% FIO2 at the time of beginning ECLS. The oxygenation index (OI) ranged from 45 to 180. Three (60%) of the patients survived. In the three patients who ultimately survived, significant improvements in pulmonary and hemodynamic parameters occurred within 96 hours of ECLS. The two patients who died showed no improvement and were removed from ECLS at 10 and 11 days; both expired within hours. The patients who expired developed significant hemodynamic instability, coagulopathy, and hemorrhage from their burn wounds. The extent and degree of burn injury did not seem to alter the outcome. Indications for considering ECLS in the pediatric burn patient are unmanageable, life threatening pulmonary insufficiency in patients that undergo a relative short course of pre-ECLS ventilator support.(ABSTRACT TRUNCATED AT 250 WORDS)
Burns↗
Comparative assessment of cultured skin substitutes and native skin autograft for treatment of full-thickness burns.
OBJECTIVE: Comparison of cultured skin substitutes (CSSs) and split-thickness autograft (STAG) was performed to assess whether the requirement for autologous skin grafts may be reduced in the treatment of massive burns. SUMMARY BACKGROUND DATA: Cultured skin substitutes consisting of collagen-glycosaminoglycan substrates populated with autologous fibroblasts and keratinocytes have been demonstrated to close full-thickness skin wounds in athymic mice and to express normal skin antigens after closure of excised wounds in burn patients. METHODS: Data were collected from 17 patients between days 2 and 14 to determine incidence of exudate, incidence of regrafting, coloration, keratinization, and percentage of site covered by graft (n = 17). Outcome was evaluated on an ordinal scale (0 = worst; 10 = best) beginning at day 14, with primary analyses at 28 days (n = 10) and 1 year (n = 4) for erythema, pigmentation, epithelial blistering, surface roughness, skin suppleness, and raised scar. RESULTS: Sites treated with CSSs had increased incidence of exudate (p = 0.06) and decreased percentage of engraftment (p < 0.05) compared with STAG. Outcome parameters during the first year showed no differences in erythema, blistering, or suppleness. Pigmentation was greater, scar was less raised, but regrafting was more frequent in CSS sites than STAG. No differences in qualitative outcomes were found after 1 year, and antibodies to bovine collagen were not detected in patient sera. CONCLUSIONS: These results suggest that outcome of engrafted CSSs is not different from STAG and that increased incidence of regrafting is related to decreased percentage of initial engraftment. Increased rates of engraftment of CSSs may lead to improved outcome for closure of burn wounds, allow greater availability of materials for grafting, and reduce requirements for donor skin autograft.
Animals↗
Anabolic impact of cimaterol in conjunction with enteral nutrition following burn trauma.
Burn injury is characterized by increased energy expenditure, weight loss, and muscle protein wasting. Studies have shown that beta 2-adrenergic agonists have anabolic properties in the presence of increased metabolism. This study investigated the effects of the beta 2-agonist cimaterol in burned animals receiving enteral nutrition. Guinea pigs with gastrostomies were given a 30% total body surface area burn and fed for 14 days. Animals received saline or cimaterol (0.15 mg/kg, SC) twice daily. Energy expenditure was determined before burn and on postburn days 3, 6, 9, and 12. On day 14, the soleus, gastrocnemius muscles, and heart were excised and weighed as a measure of muscle catabolism and anabolism. Carcass weight was determined to measure muscle catabolism. Cimaterol increased (p < 0.05) total protein content, gastrocnemius muscle, and carcass weights. The soleus muscle and heart weights, and resting metabolic rates showed no significant differences. Results suggest enteral nutrition with cimaterol decreases burn-induced muscle catabolism.
Adrenergic beta-Agonists↗
Maintenance of serum albumin levels in pediatric burn patients: a prospective, randomized trial.
A prospective, randomized trial was performed to determine whether maintaining serum albumin levels in burned pediatric patients had any effect on morbidity and mortality. Patients < 19 years of age with burns > 20% total body surface area were randomized to receive supplemental albumin to maintain levels 2.5 to 3.5 g/dL ("High Albumin") or were given albumin only if levels dropped < 1.5 g/dL ("Low Albumin") after completing burn shock resuscitation. The 36 patients in the Low Albumin group were well matched for age, burn size, depth of injury, and inhalation injury when compared with the High Albumin group (34 patients). As expected, serum albumin levels were significantly lower in the Low Albumin group when compared with the High Albumin group. No differences between groups were noted for resuscitation needs, maintenance fluid requirements, urine output, tube feedings received, days of antibiotic treatment, or ventilatory requirements. No differences in hematology, electrolytes, or nutritional laboratories were found. Finally, length of stay, complication rate, and mortality were not affected by albumin treatment. Albumin supplementation to maintain normal serum levels does not seem to be warranted in previously healthy children who suffer severe burns and who receive adequate nutrition.
Adolescent↗
The mRNA expression and in vitro production of cytokines and other proteins by hepatocytes and Kupffer cells following thermal injury.
Inflammatory cytokines and acute-phase proteins are closely interrelated, and their levels of production by various cells are increased by thermal injury. It was hypothesized that burn-mediated increases in the production of TNF and IL-6 by Kupffer cells and the production of acute phase proteins by hepatocytes are paralleled by increases in the corresponding message RNA levels in these cells. The mRNA expression of the cytokines, IL-6 and TNF alpha, and acute phase proteins, alpha-1 acid glycoprotein (alpha-1 AGP), and albumin in liver tissue were determined in rats 24 h after thermal injury. Also IL-6 and TNF alpha from in vitro cultured Kupffer cells, and alpha-1 AGP and albumin from in vitro cultured hepatocytes, and the serum levels of these proteins, were determined. An increased expression of IL-6 mRNA in liver tissue from animals of the burned group was accompanied by an elevation of IL-6 released from cultured Kupffer cells and by increased serum levels of this cytokine. Thermal injury caused a decrease in TNF mRNA but no change in the production of this cytokine by Kupffer cells, and TNF could not be found in the serum. Also, an increase in alpha-1 AGP mRNA expression following thermal injury was consistent with the increase of alpha-1 AGP production by hepatocytes and with the elevated serum level of this acute phase protein. Thermal injury caused no change in albumin mRNA expression or in the in vitro production of this negative acute phase protein, however, the serum level of albumin increased. The results suggest that thermal injury may cause alterations in the cytokine and acute phase protein mRNA levels in liver, which may cause alterations in the cellular production and serum levels of the corresponding proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute-Phase Proteins↗
Isolation of a unique melanogenic inhibitor from human skin xenografts: initial in vitro and in vivo characterization.
Previously, split-thickness human skin grafted onto athymic mice has been shown to become markedly hyperpigmented, but the factor(s) responsible for this hyperpigmentation had not been isolated. The present study describes the isolation and characterization of a potent melanogenic inhibitor from grafted human skin. Extracts from grafted skin inhibited, in a concentration-dependent manner, tyrosinase activity of normal human melanocytes and of Cloudman S91 murine melanoma in culture. Sodium dodecylsulfate-polyacrylamide gel electrophoresis analysis of extracts from pre- and post-grafted skin demonstrated the presence of a protein doublet of approximately 14 kD exclusively in the post-grafted skin. This protein inhibited both tyrosinase activity and cellular proliferation in a concentration-dependent manner. The inhibition of tyrosinase activity in normal human melanocytes was 53% at 0.5 microgram/ml concentration, whereas this inhibition was almost complete in murine melanoma cultures at 1.0 microgram/ml. The protein did not inhibit either cellular proliferation or protein synthesis in normal human fibroblast cultures, and therefore may act specifically on melanocytes. Injections of the inhibitor corresponded with a delay and reduction in the quantity of pigment in human skin 2 weeks after grafting. Multiple injections of the inhibitor into the hyperpigmented xenografts (20 weeks after grafting) reversed the hyperpigmentation with no observable inflammatory or toxic responses. The results indicate that hyperpigmented human skin xenografts contain a potent inhibitor of melanogenesis and melanocyte proliferation.
Animals↗