Actin polymerization contributes to neutrophil chemotactic dysfunction following thermal injury.

The agent(s) and mechanism(s) responsible for suppression of neutrophil chemotaxis in association with major thermal injury have not been identified. We have proposed that the reduced random motility characterizing patients' cells may contribute to their generalized chemotactic dysfunction. Here we report that actin polymerization may be responsible for the loss of neutrophil motility associated with major thermal injury. Using a fluorescent ligand specific for polymerized or filamentous actin (NBD-phallacidin) in conjunction with flow cytometry, we have discovered that peripheral blood and exudate neutrophils from patients with major thermal injury contain increased levels of actin in a stably polymerized form. Because cyclic polymerization and depolymerization of actin is essential to cell motility, we suggest that actin polymerization may contribute in a major way to the attenuation of neutrophil random and chemotactic functions induced by major thermal injury.

Serum copper and ceruloplasmin levels and urinary copper excretion in thermal injury.

Conflicting reports regarding copper status in thermal injury patients have been published. We determined serial serum-copper and serum-ceruloplasmin levels and 24-h urinary excretion of copper in 23 patients with second- and third-degree thermal burns. Throughout hospitalization, mean serum-copper concentration was significantly depressed; lowest levels were found in patients with greater than 40% total body surface area burns. Serum ceruloplasmin was also depressed, an unexpected finding because this protein is a positive acute-phase reactant poststress. Mean urinary excretion of copper was elevated, reaching 2.5 times the upper limit of normal 2 wk postburn. Depressed serum-copper levels paralleled the serum-ceruloplasmin levels rather than the increased urinary-copper losses. Further studies are required to determine the mechanism(s) of this altered copper metabolism and whether physiological or biochemical evidence of copper deficiency accompanies the observed hypocupremia.

100 second renal allografts from a single transplantation institution.

Between January 1, 1968 and March 1977, 100 of 131 patients who lost their first transplant at the University of Minnesota received a second renal allograft. Overall patient survival in the retransplanted group was 10% less than that in the dialysis group. The best results (graft function and patient survival were seen in young patients, nondiabetics, patients who received two sequential living related groups, and in those whose first graft was lost secondary to chronic rejection. The poorest results were seen in older patients (greater than 40 years), diabetics, and patients with acute rejection during the initial graft. Shared donor antigens do not affect graft outcome. These findings, although not the product of a randomized prospective study, may be useful in advising patients of the relative risks of retransplantation or hemodialysis.

Fibrin in peritonitis. I. Beneficial and adverse effects of fibrin in experimental E. coli peritonitis.

Fibrin has classically been considered a defense mechanism of the peritoneal cavity. We have studied the role of purified fibrin in the pathogenesis of intraperitoneal infection. Implantation of 0.5% bovine fibrin clots containing 2 X 10(8) E. coli into the rat peritoneal cavity reduces the 24-hour mortality rate from 100% to 0% compared to bacteria in a similar volume of saline solution. However, the 10-day mortality rate with fibrin is 90%; 100% develop intraperitoneal abscesses. Animals receiving sterile clots lyse than over 1 to 2 weeks without abscess formation. As few as 10(2) E. coli per fibrin clot produce abscesses, but 10(7) or more are required to produce death; without fibrin less than 10(7) E. coli neither kill nor produce intraperitoneal infections. Both late death and abscess size with 2 X 10(8) E. coli are directly proportional to the fibrin clot size but not the concentration of fibrin in the clot. Operative debridement of the fibrin at 4 or 24 hours completely eliminates abscess formation in surviving animals. In vitro growth of E. coli is neither stimulated nor inhibited by fibrin or fibrinogen. Fibrin delays systemic sepsis, but the entrapped bacteria cannot be easily eliminated by normal intraperitoneal bactericidal mechanisms and abscess formation occurs. Thus radical peritoneal debridement or anticoagulation may reduce the septic complications of peritonitis.

Creatine kinase as a prognostic indicator in electrical injury.

Serial serum creatine kinase (CK) and creatine kinase myocardial band isoenzyme (CK-MB) levels were obtained from 116 of 125 electrical burn patients admitted from 1976 through 1986. We divided patients into three groups (peak CK within 2 days after admission) as follows: group 1, CK less than 400 U/L; group 2, CK = 400 to 2500 U/L; group 3, CK greater than 2500 U/L. Clinical myocardial infarction (MI) was determined by ischemic ECG changes, LDH isoenzyme patterns, and clinical course. Skin grafts occurred in 2 of 24 patients from group 1, in 15 of 31 from group 2, and in 37 of 61 from group 3. Hospital stay (mean +/- SEM) was 4.6 +/- 1.3 days for group 1, 20.2 +/- 5.4 for group 2, and 37.7 +/- 3.6 for group 3. Group 1 patients required no amputations; group 2 had 1 limb and 5 digit amputations; group 3 had 22 limb and 16 digit amputations. Only three clinical MIs were found (all in group 3), although 1 of 31 patients from group 2 and 32 of 61 from group 3 had CK-MB greater than 4%. Highly elevated CK and CK-MB are associated with longer hospitalization, and a greater risk of skin grafting or amputation, than with levels less than 400 U/L. Clinical MI is rare and cannot be diagnosed by elevated CK-MB alone.

Mechanisms of the adjuvant effect of hemoglobin in experimental peritonitis. V. The significance of the coordinated iron component.

Adjuvant effects of hemoglobin, methemoglobin, hematin, and ferric nitrilotriacetate (FENTA) on the lethality of E. coli peritonitis in rats were compared. The functional importance of coordinated iron was affirmed by the findings that: (1) hematin simulated the hemoglobin effect when administered on an iron-equivalent basis and (2) hematoporphyrin was inactive at the same levels as hematin. The effects of hemoglobin and methemoglobin were virtually identical, suggesting that the oxidation state of the metallic center is immaterial, and analyses of peritoneal contents during lethal peritonitis promoted by either adjuvant revealed insignificant interconversions of these compounds. Saturation of systemic iron-binding capacity could not be detected during lethal E. coli--hemoglobin peritonitis and deliberate saturation of systemic transferrin by infusions of intravenous FENTA did not enhance the adjuvant effect of hemoglobin. The adjuvant effect of intraperitoneally administered FENTA was effectively nullified by simultaneous intraperitoneal deferoxamine injection, but the same maneuver had no effect on hemoglobin potency. Thus the adjuvant effect of hemoglobin in experimental peritonitis is functionally dependent on the iron component but cannot be explained by a non-heme iron flux. These characteristics suggest that adverse interactions of coordinated iron species with host defense chemistry will be fruitful subjects for future study.

Serum and urinary silver levels in thermal injury patients.

Although silver sulfadiazine has been used extensively as an effective topical antimicrobial agent in thermal injury patients, little is known about the cutaneous absorption of the silver moiety in these patients. Therefore, we longitudinally evaluated both serum silver concentration and 24-hour urinary excretion of silver in 23 patients with second- and third-degree thermal burns. Mean serum silver concentrations were modestly elevated throughout the patients' hospital course. Urinary excretion of silver was markedly elevated, especially in those patients with more severe burns. Indeed, in patients who had burns covering more than 60% of the total body surface area mean peak silver excretion was 1100 micrograms/24 hr (normal, less than 1 micrograms/24 hr). Thus, silver ion is absorbed across the burn wound in thermal injury patients treated with silver sulfadiazine. The 24-hour urinary excretion of silver appears to be a very sensitive indicator of cutaneous absorption in these patients. Possible implications of this cutaneous silver absorption warrant further evaluation.

Indium 111 autologous tagged leukocytes in the diagnosis of intraperitoneal sepsis.

We report the results of a new test, indium oxine in 111 scanning, in the diagnosis of postoperative infection. Indium 111 was used to label autologous polymorphonuclear leukocytes, which when reinjected migrate to sites of infection, inflammation, or both. Standard scintigraphy localizes the labeled inflammatory cells at these sites. Sixty-six scans were performed in 43 surgical patients. Thirty-seven scans were categorized as true-positive; 19 scans were categorized as true-negative. Therefore, the accuracy rate was 85%. Two scans (3%) in one patient represented false-positive results. Two scans (3%) were positive for inflammation but there was no infection present; this group was denoted as equivocal. Six scans (9%) were false-negative; false-negative scans are more likely in old lesions with poor blood supply and in areas that overlap regions of normal uptake. The noninvasive nature of the test, high accuracy rate, and ease of administration make it a potentially useful tool in the diagnosis of postoperative infection.

Necrotizing soft-tissue infections.

A variety of infections are encountered by the practicing surgeon. Uncommonly, a patient presents with minimal external manifestations of a deep surgical soft-tissue infection. Early aggressive intervention is required to minimize the morbidity in these often debilitated patients.

Scalping injuries: new technique for stabilization of flaps to the skull.

Extensive scalping injuries offer a unique challenge for tissue coverage because of the wide expanse of bone and lack of deep soft tissue or significant perforating vessels. For smaller injuries, pedicle flaps offer ideal coverage. Larger defects can be covered by omental flaps. Coverage with a free muscle flap followed by split-thickness skin grafting offers optimal long-term coverage. Two new techniques are introduced. The wire-button technique offers stabilization, and the halo frame provides good support and protection for a new free-flap graft and may increase the success rate of flaps in patients with scalping injuries.

Burns and wound management.

The evaluation and treatment of head and neck burns remains a challenge to the burn surgeon, because of the long-term emotional and psychologic effects of even the most minor change in facial appearance. Fortunately, the results currently achieved are orders of magnitude better than previously available, but they still remain far below the perfect outcome desired by both the physician and the burn victim.

Burns from hot oil and grease: a public health hazard.

We examined the incidence, etiology, and morbidity of burns due to hot oil and grease. Over a 10-year period from 1976 to 1985, of 1818 patients hospitalized for burns, 85 (4.7%) injuries were due to hot grease or oil. The mean age was 20 years; 34% of patients were less than 8 years old. The mean total body surface areas of second- and third-degree burns was 11.5% (range 0.5% to 40%), and the average length of hospital stay was 19.6 days. Fifty-eight percent of patients required split-thickness skin grafting (n = 49), three required intubation, and one required tracheostomy. Seventy-eight percent of oil burns occurred in the home. The most common circumstances consisted of children who grabbed the handle or electric cord of a frying pan and pulled the hot oil down onto themselves. (Nineteen of the 29 children were less than 8 years old (66%).) Burns due to cooking oil and grease are associated with considerable morbidity. The high boiling point, high viscosity, and potential combustibility of oil increase the potential soft-tissue damage when compared with typical scald injuries from hot water. The dangers of children pulling on the appliance, the dangers of transporting hot oil, the importance of supervision while children are cooking, and the importance of knowledge of the management of grease fires is stressed. Public education is needed to underline the potential seriousness of these burns.

Gasoline burns: the preventable cause of thermal injury.

Gasoline related burns are a significant cause of thermal injuries each year in the United States. In this retrospective review of 1858 admissions to our Regional Burn Center from 1979 to 1988, 270 (14.5%) were persons with gasoline-related injuries. Natural gas and other distillates were excluded. Most victims were male (228 of 270); mean age was 27 years; mean burn size was 25% total body surface area. There were 299 skin grafts performed on 172 patients, and there were 16 deaths. The mean length of stay decreased from 38 to 17 days (p less than 0.001) between the first and second 5-year time periods, even though there was no significant change in age or mean burn size. The majority (59%) of gasoline-related burns were the result of inappropriate or unsupervised use of gasoline. The general public is largely unaware of the dangers of gasoline, and further education in this area is needed.

Paraquat poisoning in a burn patient.

Paraquat is a bipyridyl compound widely used as a contact herbicide. Since its introduction in 1962, hundreds of deaths have occurred, usually after suicidal or accidental ingestion. Death after dermal absorption of paraquat is uncommon, but has occurred after either contact with undiluted paraquat, disruption of skin integrity, or prolonged exposure. It is the purpose of this case report to describe a patient who had fatal dermal paraquat absorption after a crop-dusting accident in which he sustained 37% TBSA burns. After 9.5 hours of cutaneous exposure, a paraquat level of 0.169 mg/ml was obtained at 20 hours, the standard lethal dose at 16 hours being 0.16 mg/ml. In light of the apparently irreversible pathophysiology of paraquat poisoning with plasma levels as low as 3 mg/L, prevention and early intervention are the best treatments. Our patient may have survived an otherwise routine thermal injury had his wounds been aggressively irrigated in the field.

Pulmonary failure in geriatric patients with burns: the need for a diagnosis-related group modifier.

One hundred eleven patients with burns who were age 60 years or older were treated from January 1984 through December 1992. Twenty-nine patients had pulmonary failure defined as 7 or more days of ventilatory support from the day of burn. The mortality rate for these patients was 41%; only four were discharged to home. The mortality rate for patients without pulmonary failure was 11%. Billing information was analyzed for 102 of the 111 patients. Charges for patients without pulmonary failure were two to three times greater than reimbursement. Charges for patients with pulmonary failure were 4 to 14 times greater than reimbursement. Reimbursement for elderly patients with burns is inadequate. Altering the Diagnosis-Related Group (DRG) definition of extensive burn to reflect the severity of injury in the geriatric population is one step toward reimbursement reform. Patients who require 7 or more days of ventilatory support after burn injury should be reimbursed under a separate DRG category or should have a DRG modifier.

Mechanisms of loss of human neutrophil chemotaxis following thermal injury.

The increased susceptibility to infection of patients with thermal injury is related to loss of host defense, which is reflected, in part, by the temporal loss of chemotactic function of leukocytic phagocytes. Our studies of patient neutrophils to define the mechanism of this phenomenon involved evaluation of both random and chemotactic migratory functions of patient neutrophils, measurement of receptors for chemotactic ligands, and measurement of receptors mediating substrate adherence of the cells. Measurements of migratory functions were made using the under-agarose technique and measurements of receptor expression were accomplished by flow cytometry using fluorescein-labeled ligand or receptor-specific antibody. We conclude that loss of chemotaxis in response to C5a/C5adesArg is the results of down-regulation of receptors for C5a and of reduced motility, and that loss of chemotaxis in response to the tripeptide FMLP is the result of reduced motility alone. Measurements of changes in the expression of "adherence" (iC3b) receptors revealed that up-regulation occurs early and can be sustained for weeks after injury. These results are taken to suggest that either hyper- or hypo-adherence could explain the loss of random migratory function observed for patient cells. Evidence of auto-oxidative alteration of cytoskeletal elements, to produce loss of random migratory function, also is reviewed. Considering the evidence for activation of the complement cascade after thermal injury C5a and C5adesArg are likely primary factors in effecting the down-regulation of C5a receptors, stimulation of secretion to mobilize iC3b receptors, and stimulation of respiration to auto-oxidize cell components. Such evidence of injury-mediated complement activation included data derived from application of a novel immunoassay for iC3b.

Halo immobilization in the treatment of burns to the head, face, and neck.

The care of burns to the head, face, and neck remains a challenge to the clinician. From 1978 to 1986, halo traction was used as an immobilizing device and as a protective frame for 31 patients with burns to the head (n = 8), face (n = 24), and neck (n = 28). The patients ranged in age from 8 months to 80 years (mean = 16 years) and had second- and third-degree burns covering a total body surface area of 8% to 75% (mean = 28%). The halo was used for an average of eight days (range one to 19 days) and served to immobilize and protect areas of fresh skin grafts, as well as to elevate and protect scalp donor sites (n = 10). Traction was initially used in patients who were confused and uncooperative, and in patients whose burns involved the neck to provide extension for prophylaxis against contractures. Treatment side effects included intermittent headache and backache, the latter occurring especially in the patients subjected to hyperextension. Eight patients (26%) complained of discomfort, which was reduced with adequate analgesia, sedation, and emotional support. The halo had to be removed from one patient after one day because of a loose pin, and in another patient after eight days because of the development of cellulitis at a pin site. Halo immobilization was used successfully to minimize graft loss in 30 of 31 patients.

Thermal injury, the inflammatory process, and wound dressing reduce human neutrophil chemotaxis to four attractants.

The purpose of this study was to assess the influence of thermal injury and the inflammatory process on chemotactic responses of neutrophils to four attractants (N-formyl-methionyl-leucyl-phenylalanine, the complement fragment C5a, interleukin-8, and leukotriene B4) under agarose, expression of Mac-1 (CD11b/CD18) adherence receptors on the cell surface, and polymerization of actin in the cell cytoplasm. Circulating neutrophils were isolated from peripheral blood, and exudate neutrophils from fluid collecting under two different wound dressings applied to abrasion sites of healthy subjects and to skin graft donor sites of patients with burns. Burn injury reduced the chemotactic responses of circulating neutrophils to all four attractants, suggesting a "global" defect in chemotactic function. Patient-exudate neutrophils collected under Tegaderm exhibited further decrements in all chemotactic responses, and patient-exudate neutrophils collected under Biobrane were nonmotile. The exudate neutrophils collected under Biobrane expressed high levels of Mac-1 receptors and irreversibly polymerized actin, which may contribute to the nonmotility of these exudate cells.

A multicenter review of toxic epidermal necrolysis treated in U.S. burn centers at the end of the twentieth century.

Toxic epidermal necrolysis (TEN) is a potentially fatal disorder that involves large areas of skin desquamation. Patients with TEN are often referred to burn centers for expert wound management and comprehensive care. The purpose of this study was to define the presenting characteristics and treatment of TEN before and after admission to regional burn centers and to evaluate the efficacy of burn center treatment for this disorder. A retrospective multicenter chart review was completed for patients admitted with TEN to 15 burn centers from 1995 to 2000. Charts were reviewed for patient characteristics, non-burn hospital and burn center treatment, and outcome. A total of 199 patients were admitted. Patients had a mean age of 47 years, mean 67.7% total body surface area skin slough, and mean Acute Physiology and Chronic Health Evaluation (APACHE II) score of 10. Sixty-four patients died, for a mortality rate of 32%. Mortality increased to 51% for patients transferred to a burn center more than one week after onset of disease. Burn centers and non-burn hospitals differed in their use of enteral nutrition (70 vs 12%, respectively, P < 0.05), prophylactic antibiotics (22 vs 37.9%, P < 0.05), corticosteroid use (22 vs 51%, P < 0.05), and wound management. Age, body surface area involvement, APACHE II score, complications, and parenteral nutrition before transfer correlated with increased mortality. The treatment of TEN differs markedly between burn centers and non-burn centers. Early transport to a burn unit is warranted to improve patient outcome.