Immunosuppression with hyperbaric oxygen.
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Animals↗
Biomedical subjects
J F Hansbrough
Publications and source records attributed to J F Hansbrough.
Biliary complications after liver transplantation: with special reference to the biliary cast syndrome and techniques of secondary duct repair.
In 93 consecutive cases of orthotopic liver transplantation, there were 24 example of biliary obstruction and eight of bile fistula formation. Six of the obstructed livers developed biliary cast formation so extensive that the smaller intrhepatic ducts became plugged to an extent that they could no longer have been treated by surgical mena. In each of the six cases, the most important causative factor was neglected obstruction of the large bile ducts with the intrahepatic lesions apparently being late and secondary. Stone and/or cast formation also occurred in other obstructed livers in the presence of bile fustulas, but these deposits were limited to the large ducts where they could have been or were removed. Although homograft bile undoubtedly has increased lithogenicity at certain posoperative times, the data from the present study have shown that biliary sludge formation essentially is always associated with defective bile duct reconstruction, and the observations have underscored the urgency with which reoperation must be considered. Techniques of secondary intervention have been described, with emphasis on conversion of cholecystojejunostomy to choledochojejunostomy. This operation has permitted salvage of homografts in eight of nine trials and the survival of seven patients.
Adolescent↗
Infections complicating orthotopic liver transplantation: a study emphasizing graft-related septicemia.
In 93 recipients of 102 orthotopic liver homografts, the incidence of bacteremia or fungemia exceeded 70%. The graft itself was usually an entry site for systemic infection after both immunologic and nonimmunologic parenchymal injury, especially if there was defective biliary drainage. The role of the homograft itself as the special infectious risk factor has prompted increased use of defunctionalized jejunal Roux limbs to reduce graft contamination. It has also stimulated very aggressive postoperative diagnostic efforts to rule out remedial mechanical complications of the transplant.
Humans↗
Modulation of suppressor cell activity and improved resistance to infection in the burned mouse.
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Animals↗
Functional electrical stimulation in intrinsic/extrinsic imbalanced burned hands.
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Adult↗
Sulfuric acid burns in a child: histologic examination as an indication of wound depth.
We present a case of extensive cutaneous chemical burns from sulfuric acid in a baby girl. The patient's age and the appearance of her wounds made it difficult to judge the depth of the wounds in the early stages of care. Because of the uniform appearance of the wounds and the large areas of injury, tangential excision was considered but delayed; the wounds were monitored with serial histologic biopsies for assessment of depth and progression of healing. The presence of viable dermal tissue and adnexal structures on histologic examination encouraged a program of observation and local wound care, which led to progressive healing of the wounds in 18 days. Histologic monitoring of the wounds proved to be a helpful adjunct in the clinical management of this difficult case.
Accidents, Home↗
Reduced wound contraction after grafting of full-thickness burns with a collagen and chondroitin-6-sulfate (GAG) dermal skin substitute and coverage with biobrane.
Full-thickness burns destroy both the epidermal and dermal tissues of the skin. This study evaluates a collagen and chondroitin-6-sulfate dermal skin substitute (graft) that was applied to excised full-thickness burns and covered with Biobrane. Experimental conditions included: (a) no burn, subcutaneous implantation of the graft; (b) burn, excision, graft, coverage with Biobrane and bandages; (c) burn, excision, no graft, coverage with Biobrane and bandages; (d) burn only. forty-one days post-surgery, subcutaneous implantation (N = 3) of the graft caused no detectable contraction or necrosis of the overlying skin, whereas all burn wounds contracted. Measurements of wounds (percentage of original wound size) showed statistically significant differences between the following treatments; (a) graft plus Biobrane (N = 10), 34%; (b) no graft plus Biobrane (N = 9), 25%; (c) untreated burns (N = 6), 16%. Semi-quantitative evaluation of time to healing indicated by spontaneous detachment of Biobrane from wounds showed that grafted, excised wounds healed in an average of 2.7 weeks, while ungrafted, excised wounds required an average of 4.3 weeks to heal. Histological appearance of healed wounds after grafting and coverage with Biobrane resembles undamaged skin without epidermal adnexal structures. Excision of full-thickness burn eschar, followed by grafting with a collagen and chondroitin-6-sulfate dermal skin substitute and coverage with Biobrane provides reduced wound contraction within a six-week period of observation compared to non-excised wounds. Both more rapid and more complete wound healing took place compared to excised wounds that were not grafted.
Animals↗
Use of overhead hooks in burn surgery.
An overhead "hook-and-pulley" system installed in the burn operating room can facilitate patient positioning and increase efficiency of the surgical team. This system can be installed easily and inexpensively; its use is recommended.
Burns↗
The use of the bone curet in debridement of the burn wound and graft recipient sites.
We describe the use of the simple bone curet for the purpose of scraping and debriding partial-thickness burn wounds and other chronic wounds encountered by the burn surgeon before autograft placement. In our experience the instrument allows more efficient and safer operating room debridement than does the standard scalpel blade.
Burns↗
The effect of thermal injury on murine neutrophil oxidative metabolism.
The ability of polymorphonuclear leukocytes to kill bacteria and yeast is reflected by cellular chemiluminescence or similarly by the production of H2O2 during oxidative metabolism. With the use of flow cytometry and 2'7' dichlorodihydrofluorescein-diacetate, we determined the direct effect of thermal injury and the indirect effect of burn serum on murine polymorphonuclear leukocyte oxidative metabolism after stimulation on days 1, 5, and 10 after 25% total body surface area burn. Control or burn peritoneal leukocytes and 10% control or burn serum were incubated in vitro with 2'7' dichlorodihydrofluorescein-diacetate for 15 minutes, then stimulated with phorbol 12-myristate 13-acetate. The change in polymorphonuclear leukocyte fluorescence was calculated from fluorescence histograms before and after stimulation. The oxidative metabolism of burn polymorphonuclear leukocytes was clearly depressed on days 5 and 10 after burn injury. Control polymorphonuclear leukocytes in the presence of day 5 burn serum produced decreased levels of H2O2, returning to normal by day 10. In general, bactericidal activity is markedly depressed on days 5 and 10 after thermal injury and may be associated with increased risk of sepsis.
Animals↗
Cyclosporine A for prolonging allograft survival in patients with massive burns.
Cyclosporine A (CsA) immunosuppression was used in three patients with massive burns to prolong skin allograft survival. Cyclosporine A kinetic studies in patients with burns revealed markedly accelerated blood clearance and high variability in drug absorption when compared with studies in renal transplantation patients. Doses required to maintain therapeutic levels varied widely. While patients were receiving adequate maintenance therapy with CsA immunosuppression the allograft was tightly adherent without gross or microscopic rejection and was indistinguishable from autograft. Ultimately, patients' wounds were permanently covered with sequential autografts by recropping limited donor sites. There were not unusual septic complications, although prophylaxis for opportunistic infections was used. The disadvantage of allograft use is its early rejection and obligatory replacement until permanent coverage with autograft can be accomplished. Cyclosporine A can prolong allograft survival and allow autograft coverage from limited donor sites in a sequential fashion. This may lead to increased survival in patients with massive burns.
Adolescent↗
Microbial contamination in allografted wound beds in patients with burns.
Microbial wound contamination has been recognized as a cause of autograft skin graft failure. Human cadaver allograft is believed to decrease or control microbial wound contamination, and by its adherence to the wound bed, to indicate a sufficiently low microbial count to allow successful application of autograft. Suboptimal "take" of more fragile cultured skin grafts after removal of adherent allograft led us to reexamine the microbial population of these wound beds. Immediately before autografts were placed, wound beds beneath adherent allograft were biopsied for quantitative microbiologic analysis. Eighty tissue biopsy specimens from 21 patients were examined. No patients had signs of infection or sepsis at the time of biopsy. Fifty-seven percent of all patients had positive cultures beneath adherent allograft skin. Twenty-one percent of all cultures revealed "infected" wound beds (greater than 100,000 colonies per gram), and 30% of all wounds were "colonized" (less than 100,000 colonies per gram). These data suggest that take and vascularization of allograft does not guarantee that a wound bed is free of microbial contamination.
Adolescent↗
Management of cutaneous manifestations of extensive purpura fulminans in a burn unit.
Purpura fulminans is a rare disease, which may have devastating cutaneous manifestations. It usually follows an infectious illness, and although it most commonly occurs in children, it can occur in adults. The pathogenesis may be related to a relative deficiency of protein C and/or protein S. A case of an adult male is presented to illustrate the management of the severe full-thickness skin loss and the use of surgical excision and allograft in this disease.
Acute Disease↗
Clinical trials of a living dermal tissue replacement placed beneath meshed, split-thickness skin grafts on excised burn wounds.
We evaluated the ability of Dermagraft (Advanced Tissue Sciences, La Jolla, Calif.), a living tissue analog that is composed of human neonatal fibroblasts, which are grown on a polyglactin acid Vicryl mesh (Ethicon Inc., Somerville, N.J.), to function as a dermal replacement when placed beneath meshed, expanded split-thickness skin grafts (MESTSGs). Full-thickness burn wounds in 17 patients with burns (mean age, 31 years; range, 6 to 69 years; mean burn size, 23.8% total body surface area) were excised to subcutaneous fat (nine patients), to fascia (three patients), or to a combination of deep dermis and fat (five patients). Dermagraft was placed over the experimental sites, which were then covered with MESTSGs. Paired control sites on each patient received MESTSGs only. The results showed that "take" of MESTSGs on control sites was slightly better than take on experimental sites that contained the Dermagraft; however, the differences were not statistically significant. Mesh interstices epithelialized over the surface of the full-thickness wound (control sites) or over the surface of Dermagraft (experimental sites). Wound biopsy specimens demonstrated no evidence of rejection of the cultured allogeneic fibroblasts and minimal inflammatory reaction to the Vicryl fibers. Evidence of continuous basement membrane formation at the epithelial-Dermagraft junction, which was identified by immunohistochemical staining for laminin and type IV collagen, was seen by day 14 beneath the healed epithelium in the skin graft interstices. The Vicryl fibers were hydrolyzed in the wound over a 2-to-4-week period, although some expulsion of fibers occurred as the healing epithelium advanced to close the MESTSG interstices. Elastic fibers were not seen in neodermal tissue in either control or experimental wounds at periods of up to 1 year after grafting. Further trials with this living tissue replacement are in progress.
Adolescent↗
Effect of indomethacin and Impact liquid diet administration on inflammatory mediator production by murine splenocytes after burn injury.
Production of prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-alpha) by various cells is increased after injury, and these mediators are implicated in the downregulation of immune responses. We attempted to modulate the production of immune suppressive mediators by inhibiting prostaglandin production in a murine model that had a burn covering 25% of the total body surface area. Two treatments were performed. One was the intraperitoneal administration of indomethacin after burn injury at 2 mg/kg day for 10 days. The control group received saline solution injections. The other treatment was the ad libitum administration of a commercial diet after burn injury for 10 days. This diet contained mixed fats, including omega-3 and omega-6 fatty acids. The control group received standard mouse food. On days 1, 5, and 10 after burn injury, spleens were removed aseptically, and splenocyte cultures were established and stimulated with phytohemagglutinin. TNF-alpha and PGE2 concentrations were determined in culture supernatants at 48 hours with the use of commercial enzyme-linked immunosorbent assay kits. Splenocytes from burned animals produced elevated levels of both mediators in culture supernatants, reaching significant levels of TNF-alpha on day 10 after burn injury and of PGE2 on days 5 and 10 after burn injury. Neither the administration of indomethacin for 10 days nor the administration of the commercial diet for 10 days decreased production of these mediators in culture. However, cells in culture may escape the in vivo regulating effects of biologic modifying agents.
Animals↗
Cytotoxicity to human leukocytes by topical antimicrobial agents used for burn care.
We tested two topical antimicrobial agents (TAAs), silver sulfadiazine and mafenide acetate, to determine their cytotoxic effects when human lymphocytes and neutrophils were incubated with the agents in vitro for 30 minutes. Dilute concentrations of both TAAs markedly inhibited neutrophil respiratory burst activity and mitogen-stimulated lymphocyte proliferation (p < 0.05). The components of silver sulfadiazine (silver and sulfadiazine) were separately tested, and each component inhibited both neutrophil and lymphocyte functions. Mafenide acetate markedly decreased intracellular Ca+2 flux in lymphocytes. The effects of the TAAs were partially reversed when cells were washed and resuspended in medium after they were exposed in vitro to the TAAs. Commonly used TAAs may contribute to local immune dysfunction in the patient with burns. Because evidence suggests that T lymphocytes may participate in wound healing, prolonged treatment with TAAs may also effect certain aspects of wound healing.
Burns↗
Composite grafts of human keratinocytes grown on a polyglactin mesh-cultured fibroblast dermal substitute function as a bilayer skin replacement in full-thickness wounds on athymic mice.
We have developed and tested in athymic mice a new, cultured, dermal-epidermal graft composed of two human cell types coupled with a biodegradable dermal scaffold. Cultured, proliferating human keratinocytes (HK) were applied to the surface of a living dermal tissue replacement that is composed of human fibroblasts cultured on a polyglactin mesh. After 4 to 6 days of coculture, proliferating HKs achieved confluency on the surface of the living dermal tissue replacement. Grafts were then transferred to full-thickness wounds on the dorsum of athymic mice. Sixteen animals were grafted, and the mean percentage of graft take (original wound area covered) on day 20 after grafting was 51.25%. Staining with antibody specific for human involucrin confirmed the presence of HKs on closed wounds, and staining with antibody specific for human laminin revealed a continuous layer of laminin at the dermal-epidermal junction on day 20. Animals closed with living dermal tissue replacement alone markedly contracted, whereas application of living dermal tissue replacement-HK grafts appeared to retard contraction. Because polyglactin mesh fibers are absorbed by hydrolysis rather than by enzymatic degradation, this living composite graft may be more resistant to destruction when placed on excised human wounds than are composite grafts, which are composed of a collagen matrix. The inclusion of the living dermal substitute may ultimately provide better skin quality than is achieved from the use of cultured keratinocytes alone. Fragility of the epidermal layer is probably due to the short-term culture of HKs on the living dermal tissue replacement, and further efforts to develop a thicker epithelial layer may improve graft durability.
Animals↗
Effects of fluid resuscitation, burn eschar excision, and blockade of afferent pain responses on bacterial translocation and acid-base balance after murine burn injury.
We tested effects of fluid resuscitation, early burn excision/grafting, and blockade of afferent stimuli from the burn wound on bacterial translocation and acid-base balance after murine burn injury. Burn excisions were performed with patients either 15 minutes or 2 hours after burn injury under anesthesia, and excised wounds were immediately closed with murine allograft skin. Twenty-four hours after 25% total body surface area (TBSA) burn injury and 48 hours after 32% TBSA injury, mesenteric lymph nodes were cultured. Incidences of bacterial translocation in 25% and 32% TBSA burns were 31.6% and 68.4% of animals, respectively. Burned animals were in severe shock, and metabolic acidosis reached a nadir 12 hours after burn injury, with base deficit -27.8 +/- 0.6 mEq/L; 5% to 10% of animals died acutely after burn injury. After excision/grafting of burned mice at 2 hours after burn injury, the incidence of bacterial translocation was unchanged (35.7% with 25% TBSA burn, 73.3% with 32% TBSA burn), and mortality did not change. When 32% TBSA excisions were performed exactly 10 minutes after burn injury, four of the 13 mice died within several hours, and five (55.5%) of the nine survivors translocated. Rates of bacterial translocation in mice receiving anesthesia or excision/grafting without burn injury were 15.0% and 20%, respectively (p = NS compared with normal mice). Subcutaneous implantation of normal or burned skin into normal animals neither elicited shock nor increased the incidence of bacterial translocation. Increasing amounts of fluid resuscitation in the 25% TBSA burn model provided only delayed improvement of acid-base balance; increased amounts of fluid did not decrease bacterial translocation.(ABSTRACT TRUNCATED AT 250 WORDS)
Acid-Base Equilibrium↗