Enhancement of incisional wound healing and neovascularization in normal rats by thrombin and synthetic thrombin receptor-activating peptides.

To better define thrombin-receptor interactions, we synthesized human thrombin peptides and identified binding-domain peptides that bind thrombin receptors and activate mitogenic signals (Glenn, K.C., G.H. Frost, J.S. Bergmann, and D.H. Carney. 1988. Pept. Res. 1:65-73). Treatment of full dermal dorsal incisions with a single topical application of thrombin receptor-activating peptide (TRAP-508) or human alpha-thrombin in saline enhances 7-d incisional breaking strength in normal rats up to 82% or 55% over saline-treated controls, respectively. Control wounds require approximately 11.5 d to achieve breaking strength equivalent to TRAP-treated wounds at day 7. Thus, a single application of TRAP accelerates healing, shifting the time course forward by up to 4.5 d. Histological comparisons at day 7 show more type I collagen, less evidence of prolonged inflammation, and an increase in number and maturity of capillaries in TRAP- and thrombin-treated incisions. Angiograms also show 50-65% more functional vascularization going across thrombin- and TRAP-treated surgical incisions. Thus, alpha-thrombin and thrombin peptides, such as those released following injury, appear to initiate or enhance signals required for neovascularization and wound healing. The ability to accelerate normal wound healing events with synthetic peptides representing receptor binding domains of human thrombin may offer new options for management of wound healing in man.

Biobrane improves wound healing in burned children without increased risk of infection.

A synthetic bilaminar membrane used as a skin substitute (Biobrane) has been shown to decrease pain and hospitalization in superficial second-degree burns. Despite these benefits, it has not been utilized universally, particularly in young children, due to a perceived increase in related infections. We propose that when this synthetic membrane is applied to superficial scald burns <25% of the total body surface area (TBSA), decreased healing times are expected without increased risk of infection. Between 1994-1999, 89 children treated within 48 h after receiving superficial partial thickness scald burns covering 5-25% TBSA with no indication of infection were seen at our hospital. Forty-one were assigned randomly to receive treatment with the skin substitute Biobrane and 48 to receive conservative treatment with topical antimicrobials and dressing changes. Comparisons of treatment were made between groups for length of hospitalization, wound healing times, and infectious complications. Children treated with Biobrane or topical antimicrobials were similar in age, race, sex, %TBSA burned, and location of burn. Those receiving Biobrane had shorter hospitalizations and healing times, which was significant for both infants and toddlers and older children. Treatment groups were not different in the use of systemic antibiotics or readmissions for infectious complications. Biobrane was removed in 5.9% of cases for non-adherence. The application of Biobrane within 48 h of superficial burns provides for shorter hospitalizations and faster healing times in children of all ages without increased risk of infection.

Rapid slide technique with dextranomer beads for bacteriologic assessment of wounds in the elderly: comparison with quantitative biopsy method.

A rapid slide technique to provide quantitative bacteriologic assessment of wounds in elderly and debilitated patients is described. It involves the use of material from dextranomer-bead (Debrisan) wound dressings to replace tissue biopsy for deciding when a wound is ready for closure or when a specific therapy is no longer efficacious. In 27 patients an 81 percent correlation was demonstrated between the bacterial count as determined by the new method and that determined by the more complicated tissue biopsy.

Comparison of silver sulfadiazine, povidone-iodine and physiologic saline in the treatment of chronic pressure ulcers.

The presence of bacteria and local infection is an important factor in the local management of chronic pressure ulcers. For successful closure of the ulcer, the bacterial count should be 10(5) or less per gram of tissue in the granulating wound. In a prospective randomized study of 45 (eventually 40) hospitalized patients, silver sulfadiazine (Silvadene) cream and povidone-iodine (Betadine) solution were compared to physiologic saline for effectiveness in preparing pressure ulcers for closure. Quantitative bacteriologic techniques on tissue biopsy specimens were used for objective evaluation. In 100 percent of the ulcers treated with silver sulfadiazine cream (15 patients) the bacterial counts were reduced to 10(5) or less per gram of tissue within the three-week test period, compared to 78.6 percent in those treated with saline (14 patients) and 63.6 percent in those treated with povidone-iodine solution (11 patients). Moreover, the ulcers treated with silver sulfadiazine cream responded more rapidly, with one-third showing bacterial levels of less than 10(5) within three days, and half within a week.

The use of specific thromboxane inhibitors to preserve the dermal microcirculation after burning.

Selective thromboxane inhibitors were evaluated as a pharmacological agent in the prevention of progressive dermal ischemia after burning. Standardized partial-thickness burns were inflicted on guinea pigs. Burned guinea pigs were separated into four groups: one served as a control, one was treated with Imidazole, one with dipyridamole, and the other with methimazole. Histology and depth of dermal perfusion were evaluated by the India ink perfusion technique. Untreated controls showed progressive dermal ischemia with complete absence of India ink-filled vessels in the dermis by 24 hours. Imidazole, dipyridamole, and methimazole improved dermal perfusion as suggested by relative levels of India Ink filling. Preservation of dermal appendages was seen secondarily to improved dermal microcirculation with an eight-fold increase in hair follicles in treated guinea pigs compared with controls. This study suggest that thromboxane plays a role in progressive dermal ischemia. Selective inhibition of thromboxane avoids the side effects associated with complete suppression of the metabolism of arachidonic acid.

Therapeutic efficacy of Biobrane in partial- and full-thickness thermal injury.

Cadaver allograft skin, porcine xenograft skin, and amniotic membranes have been proved to be adequate temporary thermal wound coverings in four clinical situations: coverage of shallow wounds while awaiting epithelialization (SW), coverage of deep wounds after eschar excision (DEW), coverage of widely meshed autograft while awaiting closure of interstices (AC), and coverage of massive donor sites (DS). This study was undertaken to evaluate the therapeutic efficacy of a new biosynthetic bilaminate dressing, Biobrane. Two hundred one applications of Biobrane were studied in 82 SW, 46 DEW, 19 AC, 54 DS. A total of 124 applications were left in place until healing occurred, with a mean healing time of 12.8 days. Sixty of SW, 10/46 DEW, 10/19 AC, and 44/54 DS remained intact until complete healing. Only four DEW, two SW, and 0 AC applications had to be removed because of suppuration. Twenty five of the applications (SW and DEW) with the Biobrane glove had rare complications.

The effect of denervation on leukocyte function in soft tissue infection.

BACKGROUND: The present study was undertaken to investigate the effect of denervation on leukocyte function in soft-tissue infection in an isolated in vivo ovine flap model. METHODS: Fifteen adult ewes were divided into three groups. An island pedicle flap was raised on the right buttock. In group I (no denervation), the cutaneous nerve remained intact, whereas in group II (acute denervation) the nerve was divided acutely. In group III (prolonged denervation) the nerve was divided 7 days before flap elevation. All flaps received intradermal inoculation of 10(7) Staphylococcus aureus, and the animals were observed for 96 hours. RESULTS: In both groups II and III, the leukocyte chemiluminescence and chemotaxis were significantly decreased when compared with group I. Furthermore, there was profound impairment of leukocyte functions in group III compared with group II. Group III also had significantly higher bacterial counts, larger septic foci, lower viable leukocyte ratios, and decreased bacterial killing compared with group I. CONCLUSIONS: Denervation, particularly over a period of time, results in increased bacterial growth of soft-tissue septic foci. This appears to be due to decreased leukocyte function resulting in diminished bacterial killing.

Significance of neutrophils and bacteria in the amniotic fluid of patients in labor.

Amniotic fluid specimens from 110 patients in labor were examined for neutrophils and bacteria. Patients with neutrophils in their amniotic fluid had significantly higher fever indices than patients with clear amniotic fluid. The highest fever indices were found in those patients who delivered by cesarean section after neutrophils were present in their amniotic fluid. Febrile morbidity was significantly reduced in a group of 24 such patients by giving prophylactic antibiotics.

Postburn gastrointestinal vasoconstriction increases bacterial and endotoxin translocation.

Splanchnic ischemia has been associated with bacterial translocation and increased endotoxin absorption from the gut. To study the effects of major burn on splanchnic circulation, minipigs were randomized to receive 40% flame burn and Parkland resuscitation or sham burn and maintenance fluids. Total and fractionated blood flow, O2 delivery and consumption, mucosal pH of the intestine, and endotoxin levels in the superior mesenteric vein were measured for 48 h, and then abdominal organs were harvested for bacteriological culture and histopathological analysis. Total mesenteric blood flow and fractionated blood flow to the mucosa-submucosa of the jejunum, cecum, and colon decreased 2 and 4 h postburn. Although mesenteric O2 consumption was unchanged, mesenteric O2 delivery and intestinal mucosal pH were decreased during the early postburn period. Concomitantly, endotoxin levels in the superior mesenteric vein were significantly elevated during the first 8 h postburn. The bacteriological cultures of the systemic tissue samples showed increased bacterial translocation in the burn group. After major burns, there is a transient selective splanchnic vasoconstriction, which is associated with intestinal mucosal acidosis and increased incidence of bacterial translocation and endotoxin absorption from the gut.

Skin testing. A valuable predictor in thermal injury?

Delayed hypersensitivity skin testing, a prognosticator of sepsis in severely injured patients, has been reported to have varied usefulness following thermal trauma. Skin tests were immediately and sequentially performed with six recall skin-test antigens on 69 patients with burns on greater than 25% of their total body surface area (TBSA). Skin tests were also immediately and sequentially performed with the same recall skin-test antigens on 42 patients with less than 25% of TBSA burned, as controls. In addition, calorie intake was recorded for all patients. Of the 69 patients with greater than 25% of TBSA burned, nine were normal, 13 were relatively anergic, and 47 were anergic. Of the patients in the less than 25% group, 13 were normal, 16 were relatively anergic, and 13 were anergic. In evaluating these data, we concluded that totally anergic patients are no more likely to die of sepsis than are normally responsive patients, nor are they more likely to have sepsis than normal and relatively anergic patients.

Candida infection with and without nystatin prophylaxis. A 11-year experience with patients with burn injury.

The incidence of opportunistic infections after thermal injury is high. Since 1985, we have been practicing Candida prophylaxis using nystatin "swish-and-swallow" and topical therapy. Patients treated between 1980 and 1984 served as controls and received no Candida prophylaxis. Although mean burn size, full-thickness injury, and age were comparable, the incidence of Candida colonization (26.7% vs 15.6%), infection (21.3% vs 10.0%), and sepsis (12.2% vs none) was significantly different between control and nystatin-treated groups, respectively. With prophylaxis, the incidence of Candida wound infection has been significantly reduced, and systemic candidiasis has been eradicated, eliminating the need for toxic systemic antifungal agents.

Mesenteric lymphadenectomy prevents postburn systemic spread of translocated bacteria.

We investigated the role of mesenteric lymph nodes in postburn systemic spread of intestinal bacteria. Group 1 minipigs (n=8) had a 40% third-degree burn. Group 2 minipigs (n=7) had the same burn injury, but their mesenteric lymph nodes were removed immediately after burn. Group 3 minipigs (n=8) had sham burn, and group 4 minipigs (n=6) had mesenteric lymph node removal under anesthesia. All minipigs were killed at 48 hours, and tissues were harvested for bacteriological culture. Group 1 showed a large number of positive cultures from several of the systemic organs. Group 2 demonstrated no positive cultures in any of the tissues except the peritoneal fluid. These data suggest that bacterial translocation occurs mainly via mesenteric lymphatics to mesenteric lymph nodes and, thence, into other systemic tissue. After major burns, mesenteric lymph nodes may become an additional focus of infection.

The effect of venous obstruction in infected pedicle flap.

A new model of soft-tissue infection is used to investigate the effect of the local wound environment on the septic focus. Island pedicle flaps were raised on the buttock of 24 adult ewes and multiply inoculated with Staphylococcus aureus. Flaps with bacterial inoculation, without compromise of venous outflow, showed distal necrosis (mean +/- SEM percent of surface area, 25.8% +/- 8.6%) and developed septic foci with bacterial counts one log less than the amount injected. Flaps with inoculation and venous outflow obstruction underwent subtotal necrosis (mean percent of surface area, 73.3% +/- 11.2%) and had counts two logs higher than the nonobstructed flaps but without discrete septic foci. Flaps without inoculation, with or without venous obstruction, survived completely. Venous outflow obstruction is shown herein to potentiate tissue necrosis by raising bacterial counts in a septic focus and preventing defensive abscess formation by the host.

Antithrombin, prekallikrein, and fibronectin levels in surgical patients.

Antithrombin (AT), prekallikrein (PK), and fibronectin (FN) levels were measured in the plasma of 290 patients. The mean (+/- SD) lowest AT level measured in 287 patients was 70% +/- 18% (normal, 75% to 120% of control). The mean lowest AT level in 81 septic patients (49% +/- 17%) was significantly lower than in the 206 patients without sepsis (78% +/- 22%). The mean AT level in 60 patients who died (42% +/- 22%) was significantly lower than in 227 patients who lived (78% +/- 19%). The mean lowest PK level measured in 71 patients was 42% +/- 17% (normal, 80% to 120%). The mean PK level in 32 septic patients (26% +/- 12%) was significantly lower than in 39 patients who were not septic (54% +/- 19%). The mean lowest FN level measured in 45 patients was 193 +/- 86 micrograms/mL (normal, 160 to 240 micrograms/mL). The mean FN level in 15 septic patients (128 +/- 72 micrograms/mL) was significantly lower than in the 30 nonseptic patients (266 +/- 84 micrograms/mL). Following AT, PK, and FN levels in critically ill surgical patients may allow earlier diagnosis and more effective treatment of sepsis.

Ciprofloxacin as a therapeutic modality in pediatric burn wound infections: efficacious or contraindicated?

BACKGROUND: Food and Drug Administration regulations state that ciprofloxacin hydrochloride may cause arthropathies. For this reason, such therapy is contraindicated in the pediatric population. However, several studies in children with cystic fibrosis have found the drug to be efficacious. Our hypothesis was that ciprofloxacin treatment is justified in the case of multiresistant organisms in burn populations. DESIGN: During a 4-year period (January 1, 1993, to December 31, 1997) we treated 56 of our pediatric burn patients with ciprofloxacin when cultures proved resistant to other antibiotics. The burn area was 65% of the total body surface area. The average patient age was 8.4 years. Of the 56 patients who received ciprofloxacin, 50 received the recommended dose. Biopsy specimens were assessed for quantitative bacteriology and antibiotic sensitivity. Radiologic review was conducted to examine for arthropathy. RESULTS: All patients showed unequivocal reduction in quantitative bacterial counts, and susceptibility to ciprofloxacin remained stable without the development of resistance. Of the 56 patients treated, 42 had a major reduction in their quantitative wound biopsies from 10(6) to less than 100 colonies per gram of tissue, while the remaining 14 were observed to have a 2- to 3-log decrease. No arthropathy was detected in any of the 56 patients receiving ciprofloxacin. Review of the patients' charts showed no documented adverse events associated with the use of ciprofloxacin. All patients survived their thermal injury and the complications associated with it without any untoward problems or complications of arthropathy. CONCLUSION: On the basis of these data, ciprofloxacin therapy in the treatment of immunosuppressed pediatric burn patients is efficacious and does not cause arthropathy.

Comparison of wound culture and bronchial lavage in the severely burned child: implications for antimicrobial therapy.

BACKGROUND: The relationship of the burn wound flora to microbial pathogens in the tracheobronchial tree has important implications for antimicrobial therapy in the severely burned patient. Management of septic complications is bolstered by surveillance quantitative wound cultures (QWC) and bronchial lavage fluid (BLF) cultures. OBJECTIVES: To compare the organisms present in BLF with those found in QWC and to determine if QWC can predict BLF results. DESIGN: Results of BLF cultures from all patients who underwent bronchial lavage from January 1, 1996, to December 31, 1996, at our institution were compared with QWC data from the same date. Criteria for a positive match included an identical antibiotic susceptibility pattern and biotype. Match rates were calculated qualitatively and quantitatively. RESULTS: In 30 (48%) of the 62 BLF cultures, there was a match between the organism identified in the BLF and the QWC. When strict quantitative criteria were applied, the match rate was only 9 (14%) of 62. Burn size and inhalation injury had no significant effect on match rate. CONCLUSIONS: Whereas the microbial pathogens were similar in the QWC and BLF, linear regression showed no value of QWC in predicting BLF culture results. The difference between qualitative and quantitative match rates suggests cross-colonization between the burn wound and tracheobronchial tree, but little to no cross-infection. The QWC and BLF cultures must be performed independently in determining antimicrobial specificity in the burned patient.

Analysis of vesicle fluid following the sting of the lionfish Pterois volitans.

Fluid aspirated from blisters following a lionfish (Pterois volitans) sting was analyzed utilizing combined capillary column gas chromatography and negative ion chemical ionization mass spectrometry. Analysis for prostaglandin F2 alpha demonstrated 16.91 ng/ml, for prostaglandin E2 0.143 ng/ml, for 6-keto-prostaglandin F1 alpha less than 0.1 ng/ml (nondetectable) and for thromboxane B2 1.65 ng/ml. Platelet aggregation studies showed that blister fluid caused aggregation of isolated platelets only, which was inhibited by heat treatment or by the presence of normal donor plasma.

Burns. Prostaglandins and thromboxane.

This article attempts to delineate the role of the prostanoids in thermal injury, based on clinical and experimental trials. It also describes the authors' concept of the cause of progressive dermal ischemia in the thermal injury and possible therapeutic measures to prevent or reduce this detrimental effect.

The effect of hemoglobin and hematocrit levels on free flap survival.

There has been experimental information suggesting that iatrogenic anemia may improve the survival of pedicled free flaps. This has been attributed to a decrease in blood viscosity secondary to hemodilution. The hemoglobin (Hb) and hematocrit (Hct) levels of 14 successful and 6 failed free flaps at the time of operation, during hospitalization, and at discharge are reviewed. There was no difference in Hb or Hct levels between successful and failed flaps. Reconstruction of traumatic defects showed an increased risk of failure. If flaps survived longer than 10-14 days, they were unlikely to fail subsequently. In conclusion, Hb and Hct levels in clinically acceptable ranges have no effect on free flap survival.

Digital replantation and revascularization. Factors affecting viability, prognosis, and pattern of injury.

As experience with digital replantation increases, preoperative factors affecting outcome are being identified. Injury type, injury cause, ischemia time, and zone of injury have previously been reported. In addition, this report analyzes the effect of injury pattern and surgical group upon outcome. This data implies a multi-factor effect on the viability of replanted/revascularized parts. The lack of thorough reporting of the factors may account for the variability seen in success rates of various centers. An injury-injury type-injury level-ischemia time classification scheme has been proposed to standardize the reporting and the discussing of amputation/devascularization injuries. In clear cut situations, injury pattern may simply reflect type of injury (e.g. avulsion); however, in those situations where the mechanism is unclear, injury patterns may provide prognostic variables valuable in predicting replant viability. Further, a multi-group, multi-surgeon service functioning within a hospital may have results comparable to those of a single surgeon or single group practice.